Distinct adiponectin profiles might contribute to differences in susceptibility to type 2 diabetes in dogs and humans.

PubMed

Verkest, K R; Rand, J S; Fleeman, L M; Morton, J M; Richards, A A; Rose, F J; Whitehead, J P

2011-08-01

Dogs develop obesity-associated insulin resistance but not type 2 diabetes mellitus. Low adiponectin is associated with progression to type 2 diabetes in obese humans. The aims of this study were to compare total and high molecular weight (HMW) adiponectin and the ratio of HMW to total adiponectin (S(A)) between dogs and humans and to examine whether total or HMW adiponectin or both are associated with insulin resistance in naturally occurring obese dogs. We compared adiponectin profiles between 10 lean dogs and 10 lean humans and between 6 lean dogs and 6 age- and sex-matched, client-owned obese dogs. Total adiponectin was measured with assays validated in each species. We measured S(A) with velocity centrifugation on sucrose gradients. The effect of total and HMW adiponectin concentrations on MINMOD-estimated insulin sensitivity was assessed with linear regression. Lean dogs had total and HMW adiponectin concentrations three to four times higher than lean humans (total: dogs 32 ± 5.6 mg/L, humans 10 ± 1.3 mg/L, P<0.001; HMW: dogs 25 ± 4.5 mg/L, humans 6 ± 1.3 mg/L, P<0.001) and a higher S(A) (dogs: 0.78 ± 0.05; humans: 0.54 ± 0.08, P = 0.002). Adiponectin concentrations and S(A) were not lower in obese dogs (0.76 ± 0.05 in both groups; P=1). Total adiponectin, HMW adiponectin, and S(A) were not associated with insulin sensitivity in dogs. We propose that differences in adiponectin profiles between humans and dogs might contribute to the propensity of humans but not dogs to develop type 2 diabetes. Dogs with chronic, naturally occurring obesity do not have selectively reduced HMW adiponectin, and adiponectin does not appear to be important in the development of canine obesity-associated insulin resistance. Copyright © 2011 Elsevier Inc. All rights reserved.

Genetic Variations of Circulating Adiponectin Levels Modulate Changes in Appetite in Response to Weight-Loss Diets.

PubMed

Ma, Wenjie; Huang, Tao; Heianza, Yoriko; Wang, Tiange; Sun, Dianjianyi; Tong, Jenny; Williamson, Donald A; Bray, George A; Sacks, Frank M; Qi, Lu

2017-01-01

Adiponectin plays key roles in regulating appetite and food intake. To investigate interactions between the genetic risk score (GRS) for adiponectin levels and weight-loss diets varying in macronutrient intake on long-term changes in appetite and adiponectin levels. A GRS was calculated based on 5 adiponectin-associated variants in 692 overweight adults from the 2-year Preventing Overweight Using Novel Dietary Strategies trial. Repeated measurements of plasma adiponectin levels and appetite-related traits, including cravings, fullness, prospective consumption, and hunger. Dietary fat showed nominally significant interactions with the adiponectin GRS on changes in appetite score and prospective consumption from baseline to 6 months (P for interaction = 0.014 and 0.017, respectively) after adjusting for age, sex, ethnicity, baseline body mass index, and baseline respective outcome values. The GRS for lower adiponectin levels was associated with a greater decrease in appetite (P < 0.001) and prospective consumption (P = 0.008) among participants consuming a high-fat diet, whereas no significant associations were observed in the low-fat group. Additionally, a significant interaction was observed between the GRS and dietary fat on 6-month changes in adiponectin levels (P for interaction = 0.021). The lower GRS was associated with a greater increase in adiponectin in the low-fat group (P = 0.02), but it was not associated with adiponectin changes in the high-fat group (P = 0.31). Our findings suggest that individuals with varying genetic architecture of circulating adiponectin may respond divergently in appetite and adiponectin levels to weight-loss diets varying in fat intake. Copyright © 2017 by the Endocrine Society

Effect of physiological determinants and cardiac disease on plasma adiponectin concentrations in dogs.

PubMed

Damoiseaux, C; Merveille, A-C; Krafft, E; Da Costa, A M; Gomart, S; Jespers, P; Michaux, C; Clercx, C; Verhoeven, C; Mc Entee, K

2014-01-01

In humans, a high concentration of adiponectin is associated with a favorable cardiovascular risk profile whereas, in patients with heart failure (HF), a high concentration of adiponectin is associated with a less favorable prognosis. To evaluate the physiological determinants of plasma adiponectin concentration in dogs and the influence of heart disease, myxomatous mitral valve disease (MMVD), and dilated cardiomyopathy (DCM). One hundred and fourteen client-owned dogs and 9 Beagles from the research colony of the Clinical Veterinary Unit of the University of Liège. We prospectively measured circulating adiponectin concentration in healthy control dogs (n = 77), dogs with MMVD (n = 22) and dogs with DCM (n = 15) of various degrees of severity. Diagnosis was confirmed by Doppler echocardiography. Plasma adiponectin concentration was measured by a canine-specific sandwich ELISA kit. An analysis of covariance showed an association between adiponectin concentration and age, neuter status, and heart disease. No association between adiponectin concentration and class of HF, sex, body condition score, body weight, circadian rhythm, or feeding was found. Plasma adiponectin concentration was negatively correlated with age (P = .001). Adiponectin was lower in neutered (P = .008) compared to intact dogs. Circulating adiponectin concentration was increased in dogs with DCM compared to healthy dogs (P = .018) and to dogs with MMVD (P = .014). Age and neutering negatively influence circulating adiponectin concentration. Plasma adiponectin concentration increased in dogs with DCM. Additional research is required to investigate if this hormone is implicated in the pathophysiology of DCM and associated with clinical outcome. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Physiological, Pharmacological, and Nutritional Regulation of Circulating Adiponectin Concentrations in Humans

PubMed Central

Swarbrick, Michael M.

2008-01-01

Abstract Adiponectin is an adipocyte hormone that links visceral adiposity with insulin resistance and atherosclerosis. It is unique among adipocyte-derived hormones in that its circulating concentrations are inversely proportional to adiposity, and low adiponectin concentrations predict the development of type 2 diabetes and cardiovascular disease. Consequently, in the decade since its discovery, adiponectin has generated immense interest as a potential therapeutic target for the metabolic syndrome and diabetes. This review summarizes current research regarding the regulation of circulating adiponectin concentrations by physiological, pharmacological, and nutritional factors, with an emphasis on human studies. In humans, plasma adiponectin concentrations are influenced by age and gender, and are inversely proportional to visceral adiposity. In vitro studies suggest that adiponectin production may be determined primarily by adipocyte size and insulin sensitivity, with larger, insulin-resistant adipocytes producing less adiponectin. While adiponectin concentrations are unchanged after meal ingestion, they are increased by significant weight loss, such as after bariatric surgery. In addition, adiponectin production is inhibited by a number of hormones, including testosterone, prolactin, glucocorticoids and growth hormone, and by inflammation and oxidative stress in adipose tissue. Smoking decreases, while moderate alcohol consumption increases, circulating adiponectin concentrations. Dietary fatty acid composition in rodents influences adiponectin production via ligand-activated nuclear receptors (PPARs); however, current evidence in humans is equivocal. In addition to PPAR agonists (such as thiazolidinediones and fibrates), a number of pharmacological agents (angiotensin receptor type 1 blockers, ACE inhibitors, and cannabinoid receptor antagonists) used in treatment of the metabolic syndrome also increase adiponectin concentrations in humans. PMID:18510434

The Rab11 Effector Protein FIP1 Regulates Adiponectin Trafficking and Secretion

PubMed Central

Moreno-Navarrete, Jose Maria; Fernandez-Real, Jose Manuel; Mora, Silvia

2013-01-01

Adiponectin is an adipokine secreted by white adipocytes involved in regulating insulin sensitivity in peripheral tissues. Secretion of adiponectin in adipocytes relies on the endosomal system, however, the intracellular machinery involved in mediating adiponectin release is unknown. We have previously reported that intracellular adiponectin partially compartmentalizes with rab 5 and rab11, markers for the early/sorting and recycling compartments respectively. Here we have examined the role of several rab11 downstream effector proteins (rab11 FIPs) in regulating adiponectin trafficking and secretion. Overexpression of wild type rab11 FIP1, FIP3 and FIP5 decreased the amount of secreted adiponectin expressed in HEK293 cells, whereas overexpression of rab11 FIP2 or FIP4 had no effect. Furthermore shRNA-mediated depletion of FIP1 enhanced adiponectin release whereas knock down of FIP5 decreased adiponectin secretion. Knock down of FIP3 had no effect. In 3T3L1 adipocytes, endogenous FIP1 co-distributed intracellularly with endogenous adiponectin and FIP1 depletion enhanced adiponectin release without altering insulin-mediated trafficking of the glucose transporter Glut4. While adiponectin receptors internalized with transferrin receptors, there were no differences in transferrin receptor recycling between wild type and FIP1 depleted adipocytes. Consistent with its inhibitory role, FIP1 expression was decreased during adipocyte differentiation, by treatment with thiazolidinediones, and with increased BMI in humans. In contrast, FIP1 expression increased upon exposure of adipocytes to TNFα. In all, our findings identify FIP1 as a novel protein involved in the regulation of adiponectin trafficking and release. PMID:24040321

Determinants of Adiponectin Levels in Patients with Chronic Systolic Heart Failure

PubMed Central

Biolo, Andreia; Shibata, Rei; Ouchi, Noriyuki; Kihara, Shinji; Sonoda, Mina; Walsh, Kenneth; Sam, Flora

2010-01-01

Adiponectin, an adipocytokine, is secreted by adipocytes and mediates anti-hypertrophic and anti-inflammatory effects in the heart. Plasma concentrations of adiponectin are decreased in obesity, insulin resistance and obesity-associated conditions such as hypertension and coronary heart disease. However, a paradoxical increase in adiponectin levels is observed in human systolic heart failure (HF). We sought to investigate the determinants of adiponectin levels in patients with chronic systolic HF. Total adiponectin levels were measured in 99 patients with stable HF and left ventricular (LV) ejection fraction (EF) <40%. Determinants of adiponectin levels by univariate analysis were included in a multivariate linear regression model. At baseline patients were 62% black, 63% male, mean age of 60±13 years, LVEF of 21±9% and a body mass index (BMI) of 30.6±6.7kg/m2. Mean adiponectin levels were 15.8±15µg/ml. Beta-blocker use, BMI, and blood urea nitrogen (BUN) were significant determinants of adiponectin levels by multivariate analysis. LV mass, structure, and LVEF were not related to adiponectin levels by multivariate analysis. Interestingly, the effect of beta-blocker therapy was most marked in non-obese patients with BMI < 30kg/m2. In conclusion, in chronic systolic HF patients, beta-blocker therapy is correlated with lower adiponectin levels, especially in non-obese patients. This relation should be taken into account when studying the complex role of adiponectin in chronic systolic HF. PMID:20381668

Similar associations of total adiponectin and high molecular weight adiponectin with cardio-metabolic risk factors in a population of overweight and obese postmenopausal women: a MONET study.

PubMed

Elisha, B; Ziai, S; Karelis, A D; Rakel, A; Coderre, L; Imbeault, P; Rabasa-Lhoret, R

2010-07-01

The aim of the study was to examine the association between total adiponectin and high molecular weight (HMW) adiponectin levels with cardio-metabolic risk factors in a population of sedentary, overweight, and obese postmenopausal women. Cross-sectional study was carried out on 55 nondiabetic sedentary overweight and obese postmenopausal women aged between 50 and 70 years. Insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp technique. Body composition and visceral fat were measured using dual X-ray absorptiometry and computed tomography, respectively. Other cardio-metabolic risk factors included: plasma lipids, hsC-reactive protein, energy expenditure (doubly labeled water), peak oxygen consumption, muscle strength (using weight training equipment) as well as total and HMW adiponectin. Correlations of total and HMW adiponectin with various cardio-metabolic risk factors were comparable. In addition, regression analysis results showed similar independent predictors of total and HMW adiponectin. Finally, the receiver operator characteristic (ROC) curves for total and HMW adiponectin to predict insulin sensitivity showed no difference between the areas under curve (AUC) (AUC total adiponectin=0.80 [95% CI: 0.66-0.95] versus AUC HMW adiponectin=0.76 [95% CI: 0.60-0.91], p=0.36). The present study indicates that HMW adiponectin does not seem to provide additional information than total adiponectin in relation to cardio-metabolic risk factors in overweight/obese postmenopausal women. (c) Georg Thieme Verlag KG Stuttgart . New York.

Adiponectin may be a biomarker of early atherosclerosis of smokers and decreased by nicotine through KATP channel in adipocytes.

PubMed

Fan, Li Hong; He, Ying; Xu, Wei; Tian, Hong Yan; Zhou, Yan; Liang, Qi; Huang, Xin; Huo, Jian Hua; Li, Hong Bin; Bai, Ling; Ma, Ai Qun

2015-01-01

Plasm adiponectin is decreased in smokers. Adiponectin is emerging as a potential key molecular marker in atherosclerosis and other cardiovascular diseases. The aim of this study was to investigate the association between serum adiponectin levels and early atherosclerosis in smokers. Furthermore, the role of the KATP channel in the down-regulation of adiponectin by smoking was preliminarily explored. We consecutively enrolled 96 men, including 50 smokers with atherosclerosis and 46 nonsmokers. Serum adiponectin was detected with enzyme-linked immunosorbent assay - in all participants. Large (C1) and small (C2) artery elasticity indices and carotid intima-media thickness (IMT) were measured as evaluation indexes of early atherosclerosis in smokers. Finally, the effect of nicotine via ATP-dependent potassium (KATP) channels on adiponectin secretion by 3T3-L1 preadipocytes was examined in vitro. Adiponectin levels of smokers were statistically negatively correlated to IMT (r = -.440; P < 0.001) and positively correlated to C1 (r = 0.448; P < 0.001) as well as C2 (r = 0.426; P = 0.002). In 3-T3-L1 preadipocytes, nicotine treatment significantly decreased adiponectin levels (P = 0.003), whereas the adiponectin level was rescued by the inhibition of KATP channel (P < 0.001). Serum adiponectin level was an independent predictor of early atherosclerosis in smokers. Nicotine might decrease adiponectin in part through altering KATP channels in adipocytes. Copyright © 2015 Elsevier Inc. All rights reserved.

Adiponectin modulates inflammatory reactions via calreticulin receptor–dependent clearance of early apoptotic bodies

PubMed Central

Takemura, Yukihiro; Ouchi, Noriyuki; Shibata, Rei; Aprahamian, Tamar; Kirber, Michael T.; Summer, Ross S.; Kihara, Shinji; Walsh, Kenneth

2007-01-01

Obesity and type 2 diabetes are associated with chronic inflammation. Adiponectin is an adipocyte-derived hormone with antidiabetic and antiinflammatory actions. Here, we demonstrate what we believe to be a previously undocumented activity of adiponectin, facilitating the uptake of early apoptotic cells by macrophages, an essential feature of immune system function. Adiponectin-deficient (APN-KO) mice were impaired in their ability to clear apoptotic thymocytes in response to dexamethasone treatment, and these animals displayed a reduced ability to clear early apoptotic cells that were injected into their intraperitoneal cavities. Conversely, adiponectin administration promoted the clearance of apoptotic cells by macrophages in both APN-KO and wild-type mice. Adiponectin overexpression also promoted apoptotic cell clearance and reduced features of autoimmunity in lpr mice whereas adiponectin deficiency in lpr mice led to a further reduction in apoptotic cell clearance, which was accompanied by exacerbated systemic inflammation. Adiponectin was capable of opsonizing apoptotic cells, and phagocytosis of cell corpses was mediated by the binding of adiponectin to calreticulin on the macrophage cell surface. We propose that adiponectin protects the organism from systemic inflammation by promoting the clearance of early apoptotic cells by macrophages through a receptor-dependent pathway involving calreticulin. PMID:17256056

Genetic Variations of Circulating Adiponectin Levels Modulate Changes in Appetite in Response to Weight-Loss Diets

PubMed Central

Ma, Wenjie; Huang, Tao; Heianza, Yoriko; Wang, Tiange; Sun, Dianjianyi; Tong, Jenny; Williamson, Donald A.; Bray, George A.; Sacks, Frank M.

2017-01-01

Context: Adiponectin plays key roles in regulating appetite and food intake. Objective: To investigate interactions between the genetic risk score (GRS) for adiponectin levels and weight-loss diets varying in macronutrient intake on long-term changes in appetite and adiponectin levels. Design, Setting, and Participants: A GRS was calculated based on 5 adiponectin-associated variants in 692 overweight adults from the 2-year Preventing Overweight Using Novel Dietary Strategies trial. Main Outcome Measures: Repeated measurements of plasma adiponectin levels and appetite-related traits, including cravings, fullness, prospective consumption, and hunger. Results: Dietary fat showed nominally significant interactions with the adiponectin GRS on changes in appetite score and prospective consumption from baseline to 6 months (P for interaction = 0.014 and 0.017, respectively) after adjusting for age, sex, ethnicity, baseline body mass index, and baseline respective outcome values. The GRS for lower adiponectin levels was associated with a greater decrease in appetite (P < 0.001) and prospective consumption (P = 0.008) among participants consuming a high-fat diet, whereas no significant associations were observed in the low-fat group. Additionally, a significant interaction was observed between the GRS and dietary fat on 6-month changes in adiponectin levels (P for interaction = 0.021). The lower GRS was associated with a greater increase in adiponectin in the low-fat group (P = 0.02), but it was not associated with adiponectin changes in the high-fat group (P = 0.31). Conclusions: Our findings suggest that individuals with varying genetic architecture of circulating adiponectin may respond divergently in appetite and adiponectin levels to weight-loss diets varying in fat intake. PMID:27841942

Common variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/2), adiponectin concentrations, and diabetes incidence in the Diabetes Prevention Program

PubMed Central

Mather, K. J.; Christophi, C. A.; Jablonski, K. A.; Knowler, W. C.; Goldberg, R. B.; Kahn, S. E.; Spector, T.; Dastani, Z.; Waterworth, D.; Richards, J. B.; Funahashi, T.; Pi-Sunyer, F. X.; Pollin, T. I.; Florez, J. C.; Franks, P. W.

2012-01-01

Aims Baseline adiponectin concentrations predict incident Type 2 diabetes mellitus in the Diabetes Prevention Program. We tested the hypothesis that common variants in the genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1, ADIPOR2) would associate with circulating adiponectin concentrations and/or with diabetes incidence in the Diabetes Prevention Program population. Methods Seventy-seven tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ (24), ADIPOR1 (22) and ADIPOR2 (31) were genotyped. Associations of SNPs with baseline adiponectin concentrations were evaluated using linear modelling. Associations of SNPs with diabetes incidence were evaluated using Cox proportional hazards modelling. Results Thirteen of 24 ADIPOQ SNPs were significantly associated with baseline adiponectin concentrations. Multivariable analysis including these 13 SNPs revealed strong independent contributions from rs17366568, rs1648707, rs17373414 and rs1403696 with adiponectin concentrations. However, no ADIPOQ SNPs were directly associated with diabetes incidence. Two ADIPOR1 SNPs (rs1342387 and rs12733285) were associated with ~18% increased diabetes incidence for carriers of the minor allele without differences across treatment groups, and without any relationship with adiponectin concentrations. Conclusions ADIPOQ SNPs are significantly associated with adiponectin concentrations in the Diabetes Prevention Program cohort. This observation extends prior observations from unselected populations of European descent into a broader multi-ethnic population, and confirms the relevance of these variants in an obese/dysglycaemic population. Despite the robust relationship between adiponectin concentrations and diabetes risk in this cohort, variants in ADIPOQ that relate to adiponectin concentrations do not relate to diabetes risk in this population. ADIPOR1 variants exerted significant effects on diabetes risk distinct from any effect of adiponectin concentrations. [Clinical Trials Registry Nos; NCT 00004992 (Diabetes Prevention Program) and NCT 00038727 (Diabetes Prevention Program Outcomes Study)] PMID:22443353

Mathematical modeling of white adipocyte exocytosis predicts adiponectin secretion and quantifies the rates of vesicle exo- and endocytosis.

PubMed

Brännmark, Cecilia; Lövfors, William; Komai, Ali M; Axelsson, Tom; El Hachmane, Mickaël F; Musovic, Saliha; Paul, Alexandra; Nyman, Elin; Olofsson, Charlotta S

2017-12-08

Adiponectin is a hormone secreted from white adipocytes and takes part in the regulation of several metabolic processes. Although the pathophysiological importance of adiponectin has been thoroughly investigated, the mechanisms controlling its release are only partly understood. We have recently shown that adiponectin is secreted via regulated exocytosis of adiponectin-containing vesicles, that adiponectin exocytosis is stimulated by cAMP-dependent mechanisms, and that Ca 2+ and ATP augment the cAMP-triggered secretion. However, much remains to be discovered regarding the molecular and cellular regulation of adiponectin release. Here, we have used mathematical modeling to extract detailed information contained within our previously obtained high-resolution patch-clamp time-resolved capacitance recordings to produce the first model of adiponectin exocytosis/secretion that combines all mechanistic knowledge deduced from electrophysiological experimental series. This model demonstrates that our previous understanding of the role of intracellular ATP in the control of adiponectin exocytosis needs to be revised to include an additional ATP-dependent step. Validation of the model by introduction of data of secreted adiponectin yielded a very close resemblance between the simulations and experimental results. Moreover, we could show that Ca 2+ -dependent adiponectin endocytosis contributes to the measured capacitance signal, and we were able to predict the contribution of endocytosis to the measured exocytotic rate under different experimental conditions. In conclusion, using mathematical modeling of published and newly generated data, we have obtained estimates of adiponectin exo- and endocytosis rates, and we have predicted adiponectin secretion. We believe that our model should have multiple applications in the study of metabolic processes and hormonal control thereof. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemerin and Adiponectin Contribute Reciprocally to Metabolic Syndrome

PubMed Central

Chu, Sang Hui; Lee, Mi Kyung; Ahn, Ki Yong; Im, Jee-Aee; Park, Min Soo; Lee, Duk-Chul; Jeon, Justin Y.; Lee, Ji Won

2012-01-01

Obesity and metabolic syndrome (MetS) are considered chronic inflammatory states. Chemerin, a novel adipokine, may play an important role in linking MetS and inflammation. We investigated the association of chemerin with inflammatory markers and with characteristics of MetS in apparently healthy overweight and obese adults. We studied 92 adults; 59 men and 33 women whose average body mass index (BMI) was 28.15±5.08 kg/m2. Anthropometric parameters, insulin resistance indices, lipid profiles, and inflammatory markers including high sensitivity C-reactive protein (hsCRP), pentraxin 3 (PTX3), adiponectin, and chemerin were measured. Controlling for age, gender, and BMI, serum chemerin level was positively correlated with body fat and serum triglyceride, and negatively correlated with adiponectin and high density lipoprotein cholesterol (HDL- C), and was not correlated with altered hsCRP or PTX3 levels. Among the low, moderate and high chemerin groups, high chemerin individuals are more likely to have lower HDL-C. Conversely, individuals in the low adiponectin group are more likely to have lower HDL-C and show more MetS phenotypic traits than moderate and high adiponectin subjects. To determine the relationships of chemerin and adiponectin to MetS and its components, participants were stratified into four groups based on their chemerin and adiponectin levels (high chemerin/high adiponectin, high chemerin/low adiponectin, low chemerin/high adiponectin, or low chemerin/low adiponectin). Participants who were in the high chemerin/low adiponectin group more likely to have dyslipidemia and MetS (OR: 5.79, 95% CI:1.00–33.70) compared to the other three group. Our findings suggest that chemerin and adiponectin may reciprocally participate in the development of MetS. PMID:22509348

Adiponectin attenuates neuronal apoptosis induced by hypoxia-ischemia via the activation of AdipoR1/APPL1/LKB1/AMPK pathway in neonatal rats.

PubMed

Xu, Ningbo; Zhang, Yixin; Doycheva, Desislava Met; Ding, Yan; Zhang, Yiting; Tang, Jiping; Guo, Hongbo; Zhang, John H

2018-05-01

Adiponectin is an important adipocyte-derived plasma protein that has beneficial effects on cardio- and cerebrovascular diseases. A low level of plasma Adiponectin is associated with increased mortality post ischemic stroke; however, little is known about the causal role of Adiponectin as well as its molecular mechanisms in neonatal hypoxia ischemia (HI). In the present study, ten-day-old rat pups were subjected to right common carotid artery ligation followed by 2.5 h hypoxia. Recombinant human Adiponectin (rh-Adiponectin) was administered intranasally 1 h post HI. Adiponectin Receptor 1 (AdipoR1) siRNA, APPL1 siRNA, LKB1 siRNA were administered through intracerebroventricular injection 48 h before HI. Brain infarct area measurement, neurological function test, western blot, Fluoro Jade C (FJC), TUNEL, and immunofluorescence staining were conducted. Results revealed that endogenous Adiponectin, AdipoR1 and APPL1 were increased in a time dependent manner after HI. Administration of rh-Adiponectin reduced brain infarct area, neuronal apoptosis, brain atrophy and improved neurological function at 24 h and 4 weeks post HI. Furthermore, rh-Adiponectin treatment increased Adiponectin, AdipoR1, APPL1, cytosolic LKB1, p-AMPK expression levels and thereby attenuated apoptosis as shown by the decreased expression of the pro-apoptotic marker, Cleaved Caspase 3 (C-Cas3), as well as the number of FJC and TUNEL positively stained neurons. AdipoR1, APPL1 and LKB1 siRNAs abolished the anti-apoptotic effects of rh-Adiponectin at 24 h after HI. Collectively, the data provided evidence that intranasal administration of rh-Adiponectin attenuated neuronal apoptosis at least in part via activating AdipoR1/APPL1/LKB1/AMPK signaling pathway. Adiponectin could represent a therapeutic target for treatment of neonatal hypoxic ischemic encephalopathy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adiponectin and Cardiac Hypertrophy in Acromegaly.

PubMed

Gurbulak, Sabriye; Akin, Fulya; Yerlikaya, Emrah; Yaylali, Guzin F; Topsakal, Senay; Tanriverdi, Halil; Akdag, Beyza; Kaptanoglu, Bunyamin

2016-01-01

Adiponectin is an adipocytes-derived hormone which has been shown to possess insulin-sensitizing, antiatherogenic, and anti-inflammatory properties. In acromegaly, the data on adiponectin is contradictory. The relationship between adiponectin levels and cardiac parameters has not been studied. The aim of this study was to find out how adiponectin levels were affected in acromegalic patients and the relationship between adiponectin levels and cardiac parameters. We included 30 subjects (15 male, 15 female), diagnosed with acromegaly and 30 healthy (10 male, 20 female) subjects. Serum glucose, insulin, GH, IGF-1 and adiponectin levels were obtained and the insulin resistance of the subjects was calculated. Echocardiographic studies of the subjects were performed. We determined that adiponectin levels were significantly higher in the acromegalic group than the control group. In the acromegalic group, there was no statistically significant relation between serum adiponectin and growth hormone (GH), or insulin-like growth factor-1 (IGF-1) levels (p = 0.3, p = 0.1). We demonstrated that cardiac function and structure are affected by acromegaly. IVST, PWT, LVMI, E/A ratio, DT, ET, IVRT, VPR, and LVESV values were increased and the results were statistically significant. In the acromegalic group, adiponectin levels were positively related with left ventricle mass index (LVMI) but this correlation was found to be statistically weak (p = 0.03). In our study, there was a positive correlation between VAI and LVM. We also could not find any correlation between VAI and adiponectin levels. Although insulin resistance and high insulin levels occur in active acromegaly patients, adiponectin levels were higher in our study as a consequence of GH lowering therapies. Our study showed that adiponectin levels may be an indicator of the cardiac involvement acromegaly. However, the usage of serum adiponectin levels in acromegalic patients as an indicator of cardiac involvement should be supported with other, wide, multi-centered studies.

Plasma adiponectin complexes have distinct biochemical characteristics.

PubMed

Schraw, Todd; Wang, Zhao V; Halberg, Nils; Hawkins, Meredith; Scherer, Philipp E

2008-05-01

Adipocytes release the secretory protein adiponectin in a number of different higher-order complexes. Once synthesized and assembled in the secretory pathway of the adipocyte, these complexes circulate as biochemically distinct and stable entities with little evidence of interchange between the different forms that include a high-molecular-weight (HMW) species, a hexamer (low-molecular-weight form), and a trimeric form of the complexes. Here, we validate a high-resolution gel filtration method that reproducibly separates the three complexes in recombinant adiponectin and adiponectin from human and murine samples. We demonstrate that the HMW form is prominently reduced in male vs. female subjects and in obese, insulin-resistant vs. lean, insulin-sensitive individuals. A direct comparison of human and mouse adiponectin demonstrates that the trimer is generally more abundant in human serum. Furthermore, when the production of adiponectin is reduced, either by obesity or in mice carrying only a single functional allele of the adiponectin locus, then the amount of the HMW form is selectively reduced in circulation. The complex distribution of adiponectin can be regulated in several ways. Both mouse and human HMW adiponectin are very stable under basic conditions but are exquisitely labile under acidic conditions below pH 7. Murine and human adiponectin HMW forms also display differential susceptibility to the presence of calcium in the buffer. A mutant form of adiponectin unable to bind calcium is less susceptible to changes in calcium concentrations. However, the lack of calcium binding results in a destabilization of the structure. Disulfide bond formation (at position C39) is also important for complex formation. A mutant form of adiponectin lacking C39 prominently forms HMW and trimer but not the low-molecular-weight form. Injection of adiponectin with a fluorescent label reveals that over time, the various complexes do not interconvert in vivo. The stability of adiponectin complexes highlights that the production and secretion of these forms from fat cells has a major influence on the circulating levels of each complex.

A novel role for adiponectin in regulating the immune responses in chronic hepatitis C virus infection.

PubMed

Palmer, Clovis; Hampartzoumian, Taline; Lloyd, Andrew; Zekry, Amany

2008-08-01

Adipose tissue releases pro-inflammatory and anti-inflammatory mediators, including adiponectin, which elicit a broad range of metabolic and immunological effects. The study aim was to determine in subjects infected with chronic hepatitis C virus (HCV) the effects of total adiponectin and its high-molecular-weight (HMW) and low-molecular-weight isoforms on HCV-specific immune responses. Serum levels of total adiponectin and its isoforms were determined by immunoassay. The ex vivo effect of adiponectin on the HCV-specific T-cell response was examined by interferon gamma (IFN-gamma) enzyme-linked immunosorbent spot and enzyme-linked immunosorbent assay cytokine assays. The role of the mitogen-activated protein kinase (MAPK) signaling pathway in mediating the adiponectin effect on T cells was also evaluated. We found that serum levels of total and HMW adiponectin were significantly decreased in subjects with chronic HCV and increased body mass index (BMI) compared with HCV-infected lean subjects. The presence of an anti-HCV specific immune response was strongly associated with lower BMI (P = 0.004) and higher serum total (P = 0.01) and HMW (P = 0.02) adiponectin. In ex vivo assays, total adiponectin and the HMW adiponectin isoform enhanced HCV-specific IFN-gamma production (P = 0.02 and 0.03, respectively). Adiponectin-R1 receptors were expressed on T cells and monocytes. In depletion experiments, the IFN-gamma response to adiponectin was entirely dependent on the simultaneous presence of both CD4 and CD8 T cells, and to a lesser extent, natural killer cells. Selective inhibition of p38MAPK activity by SB203580 abrogated the IFN-gamma response to adiponectin, whereas extracellular signal-regulated kinase 1/2 inhibition by PD98059 did not affect the response. In chronic HCV, a reciprocal association exists between BMI, adiponectin, and the anti-HCV immune responses, emphasizing the important role played by adiposity in regulating the immune response in HCV infection.

Adiponectin and catecholamine concentrations during acute exercise in children with type 1 diabetes.

PubMed

2008-06-01

Adiponectin, an adipokine secreted by the adipocyte, is inversely related to adiposity and directly related to insulin sensitivity. In type 1 diabetes mellitus (T1DM), however, data thus far are contradictory. We investigated the relationship between adiponectin and exercise inT1DM. Forty-nine children (14.5 +/- 2.0 yr, range 8-17 yr) with T1DM on an insulin pump were studied during two 75-min exercise sessions with and without continuation of the basal rate within 4 wk. Adiponectin and epinephrine concentrations were measured before and during exercise. Mean preexercise adiponectin concentration was 11.2 +/- 4.7 mg/L (range 2.7-23.0 mg/L) with a mean absolute difference of 1.7 mg/L between the 2 d. Adiponectin concentrations did not change meaningfully during exercise (mean change: -0.1 +/- 1.2 mg/L; p = 0.17). Adiponectin correlated inversely with body mass index percentile (p = 0.02) but not with age, gender, duration of diabetes, hemoglobin A1c, or preexercise glucose. However, those with higher baseline adiponectin concentrations were less likely to become hypoglycemic during exercise, 36% becoming hypoglycemic when baseline adiponectin concentration was <10 mg/L, 42% when 10 to <15 mg/L, and 15% when > or =15 mg/L (p = 0.02). Baseline epinephrine concentrations were not associated with adiponectin, and in those whose nadir glucose was < or =100 mg/dL, there was no correlation between epinephrine response and adiponectin (p = 0.16). Adiponectin concentrations are stable from day to day, are not affected by acute exercise or metabolic control, and vary inversely with adiposity. Higher adiponectin concentration appears to be associated with a decrease in hypoglycemia risk during exercise. Further studies are needed to examine whether adiponectin protects against exercise-induced hypoglycemia by directly enhancing the oxidation of alternate fuels.

Serum adipokines (adiponectin and resistin) correlation in developing gestational diabetes mellitus: pilot study.

PubMed

Siddiqui, Khalid; George, Teena P; Nawaz, Shaik Sarfaraz; Shehata, Nevene; El-Sayed, Amel Ahmed; Khanam, Latifa

2018-06-01

Adiponectin and resistin are adipose tissue-derived proteins with antagonistic actions; adiponectin has insulin sensitive properties while resistin is involved in the development of insulin resistance. We analyzed adiponectin and resistin levels in gestational diabetes mellitus (GDM) women to evaluate the association of these adipokines in a very high diabetes prevalence population. An age-matched case-control study of GDM and normal pregnant women in Saudi population. We recruited 90 pregnant women at 24-32 weeks of gestation. Glucose levels (fasting, 1, 2, and 3 h) and lipid parameters (cholesterol, triglyceride, HDL cholesterol, LDL cholesterol) were measured. Serum adiponectin and resistin levels were analyzed using Randox evidence biochip analyzer. Pearson's correlation coefficient was used to determine the association of adiponectin and resistin with GDM risk factors. GDM women showed significantly low adiponectin and high resistin levels when compared with control group. Pearson's correlation analysis of adiponectin and resistin in all the subjects with various GDM risk factors showed a negative association of adiponectin (r = -0.32, p = .05) and a positive correlation of resistin (r = 0.41, p = .01) with LDL cholesterol. This study analyzes adiponectin and resistin levels together, as accumulating evidences shows that these are involved in the pathophysiology of GDM. This is going to help to determine in conjunction with traditional risk factors the incremental value of circulating adiponectin and resistin in developing GDM.

Associations of Adiponectin with Adiposity, Insulin Sensitivity, and Diet in Young, Healthy, Mexican Americans and Non-Latino White Adults.

PubMed

Pereira, Rocio I; Low Wang, Cecilia C; Wolfe, Pamela; Havranek, Edward P; Long, Carlin S; Bessesen, Daniel H

2015-12-22

Low circulating adiponectin levels may contribute to higher diabetes risk among Mexican Americans (MA) compared to non-Latino whites (NLW). Our objective was to determine if among young healthy adult MAs have lower adiponectin than NLWs, independent of differences in adiposity. In addition, we explored associations between adiponectin and diet. This was an observational, cross-sectional study of healthy MA and NLW adults living in Colorado (U.S.A.). We measured plasma total adiponectin, adiposity (BMI, and visceral adipose tissue), insulin sensitivity (IVGTT), and self-reported dietary intake in 43 MA and NLW adults. Mean adiponectin levels were 40% lower among MA than NLW (5.8 ± 3.3 vs. 10.7 ± 4.2 µg/mL, p = 0.0003), and this difference persisted after controlling for age, sex, BMI, and visceral adiposity. Lower adiponectin in MA was associated with lower insulin sensitivity (R² = 0.42, p < 0.01). Lower adiponectin was also associated with higher dietary glycemic index, lower intake of vegetables, higher intake of trans fat, and higher intake of grains. Our findings confirm that ethnic differences in adiponectin reflect differences in insulin sensitivity, but suggest that these are not due to differences in adiposity. Observed associations between adiponectin and diet support the need for future studies exploring the regulation of adiponectin by diet and other environmental factors.

Screening for Identification of Personalized Food to Promote Adiponectin Secretion in Patients with Cancer.

PubMed

Sakaue, Miki; Maeda, Kazuhisa; Ohno, Satoshi; Ito, Toshinori

2016-07-01

Adiponectin is secreted specifically from adipose tissue. Low serum adiponectin levels may cause metabolic syndrome, which is also a risk factor for carcinogenesis. Several studies have suggested a negative correlation between adiponectin and risk of cancers. This study examined the adiponectin secretion-promoting effect of food ingredients in adipose-derived stem cells (ADSCs) obtained from patients with cancer. ADSCs from 7 lifestyle disease cancer patients were differentiated into adipocytes. Subsequently, the adipocytes were treated with 49 food constituents. The adiponectin levels in cell culture supernatants were measured after 48 and 96 h. Soy genistein extract, lychee low-molecular-weight polyphenol, olive extract and turmeric promoted adiponectin secretion. Food constituents that promoted adiponectin secretion were identified using ADSCs derived from patients. This study suggested the possibility of a new treatment approach to prevent cancer recurrence. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The role of adiponectin in reproduction: from polycystic ovary syndrome to assisted reproduction

PubMed Central

Michalakis, Konstantinos G.; Segars, James H.

2011-01-01

Objective To summarize the effects of the adipokine adiponectin on the reproductive endocrine system, from the hypothalamic-pituitary axis to the gonads and target tissues of the reproductive system. Design A Medline computer search was performed to identify relevant articles. Setting Research institution. Intervention(s) None. Result(s) Adiponectin is a hormone secreted by adipose tissue that acts to reduce insulin resistance and atherogenic damage, but it also exerts actions in other tissues. Adiponectin mediates its actions in the periphery mainly via two receptors, AdipoR1 and AdipoR2. Adiponectin receptors are present in many reproductive tissues, including the central nervous system, ovaries, oviduct, endometrium, and testes. Adiponectin influences gonadotropin release, normal pregnancy, and assisted reproduction outcomes. Conclusion(s) Adiponectin, a beneficial adipokine, represents a major link between obesity and reproduction. Higher levels of adiponectin are associated with improved menstrual function and better outcomes in assisted reproductive cycles. PMID:20561616

Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding.

PubMed

Suyama, Shigetomo; Maekawa, Fumihiko; Maejima, Yuko; Kubota, Naoto; Kadowaki, Takashi; Yada, Toshihiko

2016-08-09

Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding.

Adiponectin promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-27b through a CaMKII/AMPK/p38 signaling pathway in human chondrosarcoma cells.

PubMed

Huang, Chun-Yin; Chang, An-Chen; Chen, Hsien-Te; Wang, Shih-Wei; Lo, Yuan-Shun; Tang, Chih-Hsin

2016-09-01

Chondrosarcoma is the second most frequently occurring type of bone malignancy characterized by distant metastatic propensity. Vascular endothelial growth factor-C (VEGF-C) is the major lymphangiogenic factor, and makes crucial contributions to tumour lymphangiogenesis and lymphatic metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. In recent years, adiponectin has also been indicated as facilitating tumorigenesis, angiogenesis and metastasis. However, the effect of adiponectin on VEGF-C regulation and lymphangiogenesis in chondrosarcoma has remained largely a mystery. In the present study, we have shown a clinical correlation between adiponectin and VEGF-C, as well as tumour stage, in human chondrosarcoma tissues. We further demonstrated that adiponectin promoted VEGF-C expression and secretion in human chondrosarcoma cells. The conditioned medium from adiponectin-treated cells significantly induced tube formation and migration of human lymphatic endothelial cells. In addition, adiponectin knock down inhibited lymphangiogenesis in vitro and in vivo We also found that adiponectin-induced VEGF-C is mediated by the calmodulin-dependent protein kinase II (CaMKII), AMP-activated protein kinase (AMPK) and p38 signaling pathway. Furthermore, the expression of miR-27b was negatively regulated by adiponectin via the CaMKII, AMPK and p38 cascade. The present study is the first to describe the mechanism of adiponectin-promoted lymphangiogenesis by up-regulating VEGF-C expression in chondrosarcomas. Thus, adiponectin could serve as a therapeutic target in chondrosarcoma metastasis and lymphangiogenesis. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Maternal and Infantile Adiponectin as Marker for Anthropometric Parameters of Lactating Mothers and their Breast-Fed Infants.

PubMed

Fakhreldin, Ahmed Ragab

2018-01-01

Breast milk adiponectin could play a role in the regulation of infants' growth during lactation. The aim is to evaluate adiponectin concentration in human milk and to investigate its relationship with serum adiponectin concentration in lactating mothers and their breastfed infants and with anthropometric parameters of infants and mothers. Sixty healthy term infants and their healthy lactating mothers are included at infant age of 1 month then repeated again at the age of 4 months. All subjects included in this study were subjected to history, clinical examination, investigations including serum level of adiponectin of infants and their mothers by RIA test, human milk level of adiponectin by ELISA test. There was a significant decrease in serum adiponectin of infant and mothers and maternal breast milk at the age of 4 months when compared to them at the age of 1 month. There was a significant positive correlation between infant serum adiponection, maternal serum adiponectin and breast milk adiponectin at infant's age of 1 month and at infant's age of 4 months. There was a significant negative correlation between maternal serum adiponectin and BMI of mothers. There was a significant negative correlation between infant serum adiponectin and their weight and length of infants at the age of 1 month and at the age of 4 months. There's a metabolic link between mothers and their infants through breast milk during the first 6 months of life. A gradual decline in adiponectin level in maternal breast milk is associated with a gradual increase in infant growth up to 6 months of age.

Succination of Thiol Groups in Adipose Tissue Proteins in Diabetes

PubMed Central

Frizzell, Norma; Rajesh, Mathur; Jepson, Matthew J.; Nagai, Ryoji; Carson, James A.; Thorpe, Suzanne R.; Baynes, John W.

2009-01-01

S-(2-Succinyl)cysteine (2SC) is formed by reaction of the Krebs cycle intermediate fumarate with cysteine residues in protein, a process termed succination of protein. Both fumarate and succination of proteins are increased in adipocytes cultured in high glucose medium (Nagai, R., Brock, J. W., Blatnik, M., Baatz, J. E., Bethard, J., Walla, M. D., Thorpe, S. R., Baynes, J. W., and Frizzell, N. (2007) J. Biol. Chem. 282, 34219–34228). We show here that succination of protein is also increased in epididymal, mesenteric, and subcutaneous adipose tissue of diabetic (db/db) mice and that adiponectin is a major target for succination in both adipocytes and adipose tissue. Cys-39, which is involved in cross-linking of adiponectin monomers to form trimers, was identified as a key site of succination of adiponectin in adipocytes. 2SC was detected on two of seven monomeric forms of adiponectin immunoprecipitated from adipocytes and epididymal adipose tissue. Based on densitometry, 2SC-adiponectin accounted for ∼7 and 8% of total intracellular adiponectin in cells and tissue, respectively. 2SC was found only in the intracellular, monomeric forms of adiponectin and was not detectable in polymeric forms of adiponectin in cell culture medium or plasma. We conclude that succination of adiponectin blocks its incorporation into trimeric and higher molecular weight, secreted forms of adiponectin. We propose that succination of proteins is a biomarker of mitochondrial stress and accumulation of Krebs cycle intermediates in adipose tissue in diabetes and that succination of adiponectin may contribute to the decrease in plasma adiponectin in diabetes. PMID:19592500

The prevention and treatment of hypoadiponectinemia-associated human diseases by up-regulation of plasma adiponectin.

PubMed

Hossain, Md Murad; Mukheem, Abdul; Kamarul, Tunku

2015-08-15

Hypoadiponectinemia is characterized by low plasma adiponectin levels that can be caused by genetic factors, such as single nucleotide polymorphisms (SNPs) and mutations in the adiponectin gene or by visceral fat deposition/obesity. Reports have suggested that hypoadiponectinemia is associated with dyslipidemia, hypertension, hyperuricemia, metabolic syndrome, atherosclerosis, type 2 diabetes mellitus and various cardiovascular diseases. Previous studies have highlighted several potential strategies to up-regulate adiponectin secretion and function, including visceral fat reduction through diet therapy and exercise, administration of exogenous adiponectin, treatment with peroxisome proliferator-activating receptor gamma (PPARγ) agonists (e.g., thiazolidinediones (TZDs)) and ligands (e.g., bezafibrate and fenofibrate) or the blocking of the renin-angiotensin system. Likewise, the up-regulation of the expression and stimulation of adiponectin receptors by using adiponectin receptor agonists would be an effective method to treat obesity-related conditions. Notably, adiponectin is an abundantly expressed bioactive protein that also exhibits a wide spectrum of biological properties, such as insulin-sensitizing, anti-diabetic, anti-inflammatory and anti-atherosclerotic activities. Although targeting adiponectin and its receptors has been useful for treating diabetes and other metabolic-related diseases in experimental studies, current drug development based on adiponectin/adiponectin receptors for clinical applications is scarce, and there is a lack of available clinical trial data. This comprehensive review discusses the strategies that are presently being pursued to harness the potential of adiponectin up-regulation. In addition, we examined the current status of drug development and its potential for clinical applications. Copyright © 2015 Elsevier Inc. All rights reserved.

ADIPOQ, ADIPOR1, and ADIPOR2 Polymorphisms in Relation to Serum Adiponectin Levels and Body Mass Index in Black and White Women

PubMed Central

Cohen, Sarah S.; Gammon, Marilie D.; North, Kari E.; Millikan, Robert C.; Lange, Ethan M.; Williams, Scott M.; Zheng, Wei; Cai, Qiuyin; Long, Jirong; Smith, Jeffrey R.; Signorello, Lisa B.; Blot, William J.; Matthews, Charles E.

2012-01-01

Adiponectin is an adipose-secreted protein with influence on several physiologic pathways including those related to insulin sensitivity, inflammation, and atherogenesis. Adiponectin levels are highly heritable and several single nucleotide polymorphisms (SNPs) in adiponectin-related genes (ADIPOQ, ADIPOR1, ADIPOR2) have been examined in relation to circulating adiponectin levels and obesity phenotypes, but despite differences in adiponectin levels and obesity prevalence by race, few studies have included black participants. Using cross-sectional interview data and blood samples collected from 990 black and 977 white women enrolled in the Southern Community Cohort Study from 2002 to 2006, we examined 25 SNPs in ADIPOQ, 19 in ADIPOR1, and 27 in ADIPOR2 in relation to serum adiponectin levels and body mass index (BMI) using race-stratified linear regression models adjusted for age and percentage African ancestry. SNP rs17366568 in ADIPOQ was significantly associated with serum adiponectin levels in white women only (adjusted mean adiponectin levels = 15.9 for G/G genotype, 13.7 for A/G, and 9.3 for A/A, p=0.00036). No other SNPs were associated with adiponectin or BMI among blacks or whites. Because adiponectin levels as well as obesity are highly heritable and vary by race but associations with polymorphisms in the ADIPOQ, ADIPOR1, and ADIPOR2 genes have been few in this and other studies, future work including large populations from diverse racial groups is needed to detect additional genetic variants that influence adiponectin and BMI. PMID:21273992

The relationship between a Mediterranean diet and circulating adiponectin levels is influenced by cigarette smoking.

PubMed

Al-Attas, Omar Salem; Hussain, Tajamul; Al-Daghri, Nasser Mohammad; De Rosas, Edgard; Kazmi, Usamah; Vinodson, Benjamin

2013-01-01

Adherence to a Mediterranean diet has been shown to lower the risk of developing several chronic diseases. The ability to augment circulating adiponectin levels is proposed as an underlying mechanism mediating the beneficial effects of this diet. We aimed to examine whether the positive relationship between the Mediterranean diet and adiponectin is altered by cigarette smoking, taking potential confounders into consideration. Plasma adiponectin levels were enzymatically measured in 45 never smokers, 61 smokers and 34 ex-smokers who adhered to a Mediterranean style diet and in 41 never smokers who did not adhere to the diet. Plasma adiponectin levels increased significantly in nonsmoking diet adherents compared to nonsmoking non-diet adherents. Among the diet adherents adiponectin decreased significantly in both moderate and heavy smokers compared to never smokers and significantly increased in quitters compared to smokers. Multiple regression analysis, controlling for age, obesity, Mediterranean diet and insulin resistance revealed an independent inverse association of smoking with adiponectin. Adiponectin levels remained significant and similar in subjects stratified according to age (50 years), BMI (25 kg/m(2)) and HOMA-IR (1.6). Despite its positive effects on adiponectin, the Mediterranean diet failed to negate the adiponectin-lowering effect of cigarette smoking, demonstrating the profound and independent capacity of cigarette smoke to negatively influence human health.

Description of a local cardiac adiponectin system and its deregulation in dilated cardiomyopathy.

PubMed

Skurk, Carsten; Wittchen, Frank; Suckau, Lennart; Witt, Henning; Noutsias, Michael; Fechner, Henry; Schultheiss, Heinz-Peter; Poller, Wolfgang

2008-05-01

Despite recent advances in medical therapy, heart failure remains a leading cause for cardiovascular mortality, and its complex pathogenesis is incompletely understood. This study was performed to identify possible new therapeutic targets in dilated cardiomyopathy (DCM). Oligonucleotide microarray analysis was performed on endomyocardial biopsies (EMBs) from patients with early DCM (LVEDD > or = 55 mm, LVEF < or = 55%, n = 5) and control subjects (LVEDD < 55 mm, LVEF > 60%, no cardiac pathology, n = 4). Adiponectin, an adipocytokine involved in cellular metabolism, survival, and immunmodulation, was six-fold downregulated in DCM patients. Microarray data for adiponectin were confirmed by TaqMan-PCR (9.2-fold downregulation, control n= 9 vs. DCM n= 9, respectively, P < 0.05). Immunohistological analysis of EMBs showed significant downregulation of cardiac adiponectin protein expression independent of serum adiponectin (P = 0.36, ns) or serum TNFalpha concentrations (P = 0.46, ns). Neither the adiponectin receptor 1 (adipo-R1) nor adipo-R2 was deregulated in early DCM. Adiponectin mRNA and protein downregulation were confirmed in explanted hearts of patients with advanced DCM (LVEF < 25%, n= 8). In vitro, adiponectin incubation of neonatal rat ventricular myocytes led to activation of the pro-survival kinase PKB/Akt, increased eNOS-phosphorylation, and prevented stress-induced apoptosis of cardiomyocytes in an Akt-dependent manner. Moreover, inhibition of adiponectin secretion was accompanied by an increase in the expression of the cytokine and its receptors. These data indicate the existence of a local cardiac adiponectin system regulated independent of adiponectin and TNFalpha serum levels and its disturbance in cardiac pathology. The study suggests a role for adiponectin in the pathogenesis of DCM and implicates the adipocytokine as a possible future therapeutic target in DCM.

Total and high molecular weight adiponectin are elevated in patients with Laron syndrome despite marked obesity.

PubMed

Kanety, Hannah; Hemi, Rina; Ginsberg, Shira; Pariente, Clara; Yissachar, Eleanor; Barhod, Ehud; Funahashi, Tohru; Laron, Zvi

2009-12-01

Patients with Laron syndrome (LS; primary GH insensitivity) caused by molecular defects of the GH receptor gene, are characterized by dwarfism, profound obesity, and hyperlipidemia. The aim of the current study was to evaluate adiponectin levels in LS, as obesity is known to be associated with low adiponectin. We studied nine untreated LS adult patients (5 males, 4 females) and six girls with LS receiving once-daily treatment by IGF1. Total and high molecular weight (HMW) adiponectin levels, adiponectin multimers distribution, and metabolic indices were analyzed in serum samples obtained during several years of follow-up. Adiponectin levels in the severely obese adult LS patients (percent body fat; females 61.0+/-2.5%, males 40.6+/-8.1%) were two- to three-fold higher than those reported for subjects of corresponding age, gender and degree of adiposity. Total adiponectin was significantly higher in females compared with males (21.4+/-3.5 vs 10.2+/-4.6 microg/ml, P<0.001). The elevated adiponectin in LS subjects was associated with an increased abundance of the HMW isoform, and positively correlated with body fat percentage (r=0.65, P=0.017) and leptin (r=0.65, P=0.012). There was no correlation between adiponectin levels (total and HMW) and the degree of insulin resistance in LS subjects or their blood lipids levels. Adiponectin was also high in young girls with LS (22.9+/-7.4 microg/ml) and did not change during long-term IGF1 replacement therapy. Adiponectin hypersecretion in LS, despite profound obesity, suggests that GH activity may negatively impact adiponectin secretion from adipocytes.

Expression of adiponectin and adiponectin receptors in human pituitary gland and brain.

PubMed

Psilopanagioti, Aristea; Papadaki, Helen; Kranioti, Elena F; Alexandrides, Theodore K; Varakis, John N

2009-01-01

Adiponectin and its receptors, AdipoR1 and AdipoR2, constitute integral components of energy homeostatic mechanism in peripheral tissues. Recent studies have implicated adiponectin in central neural networks regulating food intake and energy expenditure. The present study aimed at investigating the possible expression and distribution of adiponectin and its receptors in human pituitary gland, hypothalamus and different brain areas. Sections of the pituitary gland, hypothalamus and adjacent basal forebrain area, cerebrum and cerebellum from 35 autopsy cases, were examined using HE, PAS-Orange G, luxol fast blue/cresyl violet stains and single and double immunohistochemistry using adiponectin, AdipoR1, AdipoR2, choline acetyltransferase, FSH, LH, TSH, GH, ACTH and prolactin-specific antibodies. Age and BMI mean values +/- SD of the autopsy cases were 56 +/- 18 years and 27 +/- 5 kg/m(2), respectively. Strong adiponectin expression was observed in pituitary gland. In pars distalis (PD), adiponectin localized in GH, FSH, LH and TSH-producing cells and in pars tuberalis (PT) in FSH, LH and TSH-producing cells. Strong to moderate expression of AdipoR1 and AdipoR2 was observed in PD by the same cell types as adiponectin. No immunoreactivity for adiponectin receptors was noted in cells of PT. Intense AdipoR1 immunostaining was observed in neurons of lateral hypothalamic area and of nucleus basalis of Meynert (NBM). Adiponectin and its receptors expression in human pituitary might indicate the existence of a local system, modulating endocrine axes. Furthermore, the presence of AdipoR1 in hypothalamus and NBM suggests that adiponectin may participate in central neural signaling pathways controlling energy homeostasis and higher brain functions.

Adiponectin promotes hyaluronan synthesis along with increases in hyaluronan synthase 2 transcripts through an AMP-activated protein kinase/peroxisome proliferator-activated receptor-{alpha}-dependent pathway in human dermal fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamane, Takumi; Kobayashi-Hattori, Kazuo; Oishi, Yuichi, E-mail: y3oishi@nodai.ac.jp

2011-11-18

Highlights: Black-Right-Pointing-Pointer Adiponectin promotes hyaluronan synthesis along with an increase in HAS2 transcripts. Black-Right-Pointing-Pointer Adiponectin also increases the phosphorylation of AMPK. Black-Right-Pointing-Pointer A pharmacological activator of AMPK increases mRNA levels of PPAR{alpha} and HAS2. Black-Right-Pointing-Pointer Adiponectin-induced HAS2 mRNA expression is blocked by a PPAR{alpha} antagonist. Black-Right-Pointing-Pointer Adiponectin promotes hyaluronan synthesis via an AMPK/PPAR{alpha}-dependent pathway. -- Abstract: Although adipocytokines affect the functions of skin, little information is available on the effect of adiponectin on the skin. In this study, we investigated the effect of adiponectin on hyaluronan synthesis and its regulatory mechanisms in human dermal fibroblasts. Adiponectin promoted hyaluronan synthesis alongmore » with an increase in the mRNA levels of hyaluronan synthase 2 (HAS2), which plays a primary role in hyaluronan synthesis. Adiponectin also increased the phosphorylation of AMP-activated protein kinase (AMPK). A pharmacological activator of AMPK, 5-aminoimidazole-4-carboxamide-1{beta}-ribofuranoside (AICAR), increased mRNA levels of peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}), which enhances the expression of HAS2 mRNA. In addition, AICAR increased the mRNA levels of HAS2. Adiponectin-induced HAS2 mRNA expression was blocked by GW6471, a PPAR{alpha} antagonist, in a concentration-dependent manner. These results show that adiponectin promotes hyaluronan synthesis along with increases in HAS2 transcripts through an AMPK/PPAR{alpha}-dependent pathway in human dermal fibroblasts. Thus, our study suggests that adiponectin may be beneficial for retaining moisture in the skin, anti-inflammatory activity, and the treatment of a variety of cutaneous diseases.« less

High-molecular-weight adiponectin levels in healthy, community-dwelling, elderly Japanese volunteers: a 5-year prospective observational study.

PubMed

Otsuka, Hiromasa; Yanai, Mitsuru; Kobayashi, Hiroki; Haketa, Akira; Hara, Motohiko; Sugama, Kaoru; Kato, Kimitoshi; Soma, Masayoshi

2017-10-19

Serum adiponectin levels are associated with frailty and cardiovascular diseases. Longitudinal changes in adiponectin levels might enhance our understanding of age-related conditions and diseases. This prospective observational study aimed to: (1) elucidate age-related changes in high-molecular-weight (HMW) adiponectin levels; and (2) identify variables predictive of elevated HMW adiponectin levels and the association with well-known adiponectin single-nucleotide polymorphisms (SNPs) in healthy, elderly Japanese participants. Healthy elderly volunteers (n = 196; 55 men and 141 women; median age 72.0 years; range 69.0-75.0 years) underwent anthropometric and physical function measurements, as well as laboratory tests at baseline and the 5-year follow-up. HMW adiponectin levels were significantly higher in women than in men (8.4, 5.3-11.9 vs. 5.7, 3.1-9.0 μg/mL; p < 0.001) at baseline and decreased significantly at follow-up in women (7.7, 4.8-11.2 μg/mL; p < 0.001), but not in men. In the multiple regression analysis, high-density lipoprotein cholesterol levels and body weight were independent predictors of HMW adiponectin levels. The rate of change in HMW adiponectin levels was inversely correlated with the rates of change in body weight, body mass index, and knee leg extension strengths, and positively correlated with rates of change in high-density lipoprotein cholesterol and one-leg standing time. There were no significant differences in HMW adiponectin levels among SNPs. Decreasing HMW adiponectin levels might lead to an increased risk of cardiovascular diseases in elderly women. HMW adiponectin levels significantly decreased over a 5-year period in community-dwelling elderly Japanese women.

A reduction in both visceral and subcutaneous fats contributes to increased adiponectin by lifestyle intervention in the Diabetes Prevention Program.

PubMed

Zhang, Chao; Luo, Hao; Gao, Feng; Zhang, Chun-Ting; Zhang, Ren

2015-06-01

Adiponectin, an insulin-sensitizing adipokine, confers protection against type 2 diabetes. Although adiponectin is secreted exclusively from fat, contributions of visceral adipose tissue (VAT) versus subcutaneous adipose tissue (SAT) to adiponectin levels have not been fully understood. We aimed to examine correlations between changes in VAT and SAT volumes and changes in adiponectin levels. Here, we have investigated the correlations between ΔVAT and ΔSAT with Δadiponectin in participants of the Diabetes Prevention Program, a clinical trial investigating the effects of lifestyle changes and metformin versus placebo on the rate of developing type 2 diabetes. Data on VAT and SAT volumes, measured by computed tomography, and on adiponectin levels at both baseline and 1-year follow-up were available in 321 men and 626 women. In men, Δadiponectin was highly significantly correlated with both ΔSAT (r s  = -0.329) and ΔVAT (r s  = -0.413). Likewise, in women, Δadiponectin was correlated with both ΔSAT (r s  = -0.294) and ΔVAT (r s  = -0.348). In the lifestyle arm, Δadiponectin remained highly significantly correlated with ΔSAT and ΔVAT in men (r s  = -0.399 and r s  = -0.460, respectively), and in women (r s  = -0.372 and r s  = -0.396, respectively), with P < 0.001 for all above correlations. We conclude that for both men and women, adiponectin changes are highly significantly correlated with changes in both SAT and VAT and that exercise- and weight-loss-induced reduction in both SAT and VAT contributes to the increased adiponectin.

Total and high molecular weight adiponectin and ethnic-specific differences in adiposity and insulin resistance: a cross-sectional study

PubMed Central

2013-01-01

Background Ethnic-specific differences in insulin resistance (IR) are well described but the underlying mechanisms are unknown. Adiponectin is an insulin sensitizing adipocytokine that circulates as multiple isoforms, with high molecular weight (HMW) adiponectin associated with greatest insulin sensitivity. The objective of this study is to determine if plasma total and HMW adiponectin concentrations underlie ethnic-specific differences in IR. Methods Healthy Canadian Aboriginal, Chinese, European, and South Asian adults (N = 634) were assessed for sociodemographics; lifestyle; fasting plasma insulin, glucose, and total and HMW adiponectin; and adiposity measures [BMI, waist circumference, waist-to-hip ratio, percent body fat, and subcutaneous and visceral adipose tissue (quantified by computed tomography)]. The homeostasis model assessment-insulin resistance (HOMA-IR) assessed IR. Results South Asians had the greatest HOMA-IR, followed by Aboriginals, Chinese, and Europeans (P < 0.001). Plasma total and HMW adiponectin concentrations were lower in Chinese and South Asians than Aboriginal and Europeans (P < 0.05). Total and HMW adiponectin were inversely associated with HOMA-IR (P < 0.001). Ethnicity modified the relationship between HMW adiponectin and HOMA-IR with stronger effects observed in Aboriginals (P = 0.001), Chinese (P = 0.002), and South Asians (P = 0.040) compared to Europeans. This was not observed for total adiponectin (P = 0.431). At mean total adiponectin concentrations South Asians had higher HOMA-IR than Europeans (P < 0.001). Conclusions For each given decrease in HMW adiponectin concentrations a greater increase in HOMA-IR is observed in Aboriginals, Chinese, and South Asians than Europeans. Ethnic-specific differences in HMW adiponectin may account for differences in IR. PMID:24225161

The benefits of ω-3 supplementation depend on adiponectin basal level and adiponectin increase after the supplementation: A randomized clinical trial.

PubMed

Barbosa, Milena Maria de Araújo Lima; Melo, Alexandra Lorenzzi Trinanes Raposo de; Damasceno, Nágila Raquel Teixeira

2017-02-01

The aim of this study was to analyze whether ω-3 supplementation improves cardiometabolic profile in individuals with cardiovascular risk factors and to determine the effect of adiponectin levels on these changes. In this double-blind, placebo-controlled, 2-mo clinical trial, we randomized 80 individuals of both sexes (mean age 52 y) with at least one cardiovascular risk factor (excess weight, hypertension, dyslipidemia, diabetes, or smoking) into two groups: ω-3 (supplemented with 3 g/d of fish oil containing 37% eicosapentaenoic acid and 23% docosahexaenoic acid) and placebo (3 g/d of sunflower oil containing 65% linoleic acid). At baseline and after the intervention, we evaluated serum adiponectin, leptin, lipid profile, apolipoproteins (apo), electronegative low-density lipoprotein (LDL[-]), and glucose metabolism (glucose and insulin). After supplementation, the ω-3 group showed an increase in serum adiponectin. After stratifying the ω-3 group by adiponectin concentration at baseline, participants with lower adiponectin concentration showed a higher reduction of total cholesterol, LDL, LDL/high-density lipoprotein ratio, LDL/apo B, and LDL(-). Individuals with a higher variation of adiponectin concentration after ω-3 supplementation presented with reduced blood glucose. The variation of serum adiponectin induced by ω-3 supplementation was negatively correlated with the Framingham and Adult Treatment Panel IV scores (r = -0.4 and P < 0.05 for both). Adiponectin is shown as one of the mechanisms by which ω-3 improves cardiometabolic profile in persons with cardiovascular risk. Moreover, the benefit varies according to the adiponectin basal level and adiponectin variation after supplementation. Copyright © 2016 Elsevier Inc. All rights reserved.

Regulation of adiponectin production by insulin: interactions with tumor necrosis factor-α and interleukin-6.

PubMed

Hajri, Tahar; Tao, Huan; Wattacheril, Julia; Marks-Shulman, Pamela; Abumrad, Naji N

2011-02-01

Obesity is often associated with insulin resistance, low-grade systemic inflammation, and reduced plasma adiponectin. Inflammation is also increased in adipose tissue, but it is not clear whether the reductions of adiponectin levels are related to dysregulation of insulin activity and/or increased proinflammatory mediators. In this study, we investigated the interactions of insulin, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in the regulation of adiponectin production using in vivo and in vitro approaches. Plasma adiponectin and parameters of insulin resistance and inflammation were assessed in a cohort of lean and obese insulin-resistant subjects. In addition, the effect of insulin was examined in vivo using the hyperinsulinemic-euglycemic clamp, and in adipose tissue (AT) cultures. Compared with lean subjects, the levels of total adiponectin, and especially the high-molecular-weight (HMW) isomer, were abnormally low in obese insulin-resistant subjects. The hyperinsulinemic clamp data confirmed the insulin-resistant state in the obese patients and showed that insulin infusion significantly increased the plasma adiponectin in lean but not obese subjects (P < 0.01). Similarly, insulin increased total adiponectin release from AT explants of lean and not obese subjects. Moreover, expression and secretion of TNF-α and IL-6 increased significantly in AT of obese subjects and were negatively associated with expression and secretion of adiponectin. In 3T3-L1 and human adipocyte cultures, insulin strongly enhanced adiponectin expression (2-fold) and secretion (3-fold). TNF-α, and not IL-6, strongly opposed the stimulatory effects of insulin. Intriguingly, the inhibitory effect of TNF-α was especially directed toward the HMW isomer of adiponectin. In conclusion, these studies show that insulin upregulates adiponectin expression and release, and that TNF-α opposes the stimulatory effects of insulin. A combination of insulin resistance and increased TNF-α production could explain the decline of adiponectin levels and alterations of isomer composition in plasma of obese insulin-resistant subjects.

Adiponectin is required for maintaining normal body temperature in a cold environment

USDA-ARS?s Scientific Manuscript database

Thermogenic impairment promotes obesity and insulin resistance. Adiponectin is an important regulator of energy homeostasis. While many beneficial metabolic effects of adiponectin resemble that of activated thermogenesis, the role of adiponectin in thermogenesis is not clear. In this study, we inves...

Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding

PubMed Central

Suyama, Shigetomo; Maekawa, Fumihiko; Maejima, Yuko; Kubota, Naoto; Kadowaki, Takashi; Yada, Toshihiko

2016-01-01

Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding. PMID:27503800

Modulation of ovarian steroidogenesis by adiponectin during delayed embryonic development of Cynopterus sphinx.

PubMed

Anuradha; Krishna, Amitabh

2014-09-01

The aim of present study was to evaluate role of adiponectin in ovarian steroidogenesis during delayed embryonic development of Cynopterus sphinx. This study showed significantly low circulating adiponectin level and a decline in expression of adiponectin receptor 1 (AdipoR1) in the ovary during the period of delayed embryonic development as compared with the normal development. The adiponectin treatment in vivo during the period of delayed development caused significantly increased in circulating progesterone and estradiol levels together with increased expression of AdipoR1 in the ovary. The in vitro study confirmed the stimulatory effect of adiponectin on progesterone synthesis. Both in vivo and in vitro studies showed that the effects of adiponectin on ovarian steroidogenesis were mediated through increased expression of luteinizing hormone-receptor, steroidogenic acute regulatory protein and 3β-hydroxyl steroid dehydrogenase enzyme. The adiponectin treatment may also promote progesterone synthesis by modulating ovarian angiogenesis, cell survival and rate of apoptosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Canine adiponectin: cDNA structure, mRNA expression in adipose tissues and reduced plasma levels in obesity.

PubMed

Ishioka, K; Omachi, A; Sagawa, M; Shibata, H; Honjoh, T; Kimura, K; Saito, M

2006-04-01

Adiponectin is a protein synthesized and secreted by adipocytes. Decreased adiponectin is responsible for insulin resistance and atherosclerosis associated with human obesity. We obtained a cDNA clone corresponding to canine adiponectin, whose nucleotide and deduced amino acid sequences were highly identical to those of other species. Adiponectin mRNA was detected in adipose tissues, but not in other tissues, of dogs. When 22 adult beagles were given a high-energy diet for 14 weeks, they became obese, showing heavier body weights, higher plasma leptin concentrations, but lower plasma adiponectin concentrations. The adiponectin concentrations of plasma samples collected from 71 dogs visiting veterinary practices were negatively correlated to plasma leptin concentrations, being lower in obese than non-obese dogs. These results are compatible with those reported in other species, and suggest that adiponectin is an index of adiposity and a target molecule for studies on diseases associated with obesity in dogs.

Leptin to adiponectin ratio in preeclampsia.

PubMed

Khosrowbeygi, A; Ahmadvand, H

2013-04-01

The aim of the present study was to assess leptin/adiponectin ratio in preeclamptic patients compared with normal pregnant women. A cross-sectional study was designed. The study population consisted of 30 preeclamptic patients and 30 healthy pregnant women. Serum levels of total leptin and adiponectin were assessed using commercially available enzyme-linked immunosorbent assay methods. The one-way ANOVA and Student's t tests and Pearson's correlation analysis were used for statistical calculations. Levels of leptin and adiponectin were also adjusted for BMI. A p-value < 0.05 was considered statistically significant. The leptin/adiponectin ratio was increased significantly in preeclamptic patients. The leptin/adiponectin ratio was significantly higher in severe preeclamptic patient than in mild preeclampsia. Adjusted leptin/adiponectin ratio was also significantly increased in preeclamptic patients than in normal pregnant women. The findings of the present study suggest that the leptin/adiponectin ratio was increased in preeclamsia and imbalance between the adipocytokines could be involved in the pathogenesis of preeclampsia.

[Evaluation of adiponectin level in children and adolescents with diabetes type 1].

PubMed

Peczyńska, Jadwiga; Urban, Mirosława; Głowińska, Barbara; Florys, Bozena

2008-01-01

Adipose tissue is not only an energy storage place, but it also secretes numerous "adipocytokines" - substances that have systemic influence. Adiponectin has an anti-inflammatory, antiatherogenic properties and increases insulin sensitivity. It is emphasized that adiponectin levels are different in type 1 and type 2 diabetes. was to evaluate adiponectin levels in young patients with diabetes type 1, and to analyse of the correlation between adiponectin and: BMI, lipid parameters, glomerular filtration rate and microalbuminuria. The study group was formed by 95 patients from the Outpatient Diabetology Department 2nd Department of Children's Diseases, 45 girls and 50 boys, aged from 7 to 20 years (mean - 14.97 yrs) suffering from diabetes from 1 to 17 years (mean 6.68 yrs). Control group consisted of healthy children, age matched, without family history of cardiovascular diseases. In all patients anthropometric measurements were performed (BMI was calculated), metabolic control was evaluated on the basis of HbA1c level, microalbuminuria was studied in 24 hour urine sample. We assessed glomerular filtration rate (endogenous creatinine clearance), lipid parameters and adiponectin level. In children and adolescents with diabetes type 1 we found significantly higher levels of adiponectin compared to control group: 32.72+/-13.49 vs. 26.53+/-7.63 ug/ml; p=0.024. Adiponectin level was higher in girls than in boys (33.56 vs. 28.75 ug/ml; p=0.036). Adiponectin level did not depend on metabolic control and on diabetes duration. We found a statistically significant negative correlation between adiponectin and creatinine (r=-0.26; p=0.011). In patients with diabetic complications we found insignificantly lower adiponectin level compared to patients without complications (30.99+/-14.29 vs. 33.67+/-11.68 ug/ml; p=0.35). 1. In patients with diabetes type 1 significantly higher level of adiponectin was found compared to healthy control group. 2. Adiponectin level correlated negatively with creatinine level end microalbuminuria. 3. Elevated level of adiponectin in patients without diabetic complications may help to explain the pathogenesis of diabetic angiopathy.

Expression profiles and associations of adiponectin and adiponectin receptors with intramuscular fat in Tibetan chicken.

PubMed

Zhang, R; Lin, Y; Zhi, L; Liao, H; Zuo, L; Li, Z; Xu, Y

2017-04-01

1. Adiponectin and its receptors (ADIPOR1 and ADIPOR2) are novel endocrine systems that act at various levels to modulate glucose and lipid metabolism. This study was designed to investigate the spatial expression of adiponectin, ADIPOR1 and ADIPOR2 genes in various tissues in Tibetan chicken. The temporal expression of adiponectin and its receptor mRNAs were also studied in adipose tissue, breast muscle and thigh muscle and the correlations of the levels of adiponectin, ADIPOR1 and ADIPOR2 mRNA with the contents of intramuscular fat in breast muscle and thigh muscle of Tibetan chicken were determined. 2. Quantitative real-time PCR detected chicken adiponectin, ADIPOR1 and ADIPOR2 mRNA transcripts in heart, liver, spleen, lung, kidney, skeletal muscle and adipose tissue. 3. Adipose tissue contained the highest amount of adiponectin mRNA followed by the kidney and liver. The expression levels of ADIPOR1 mRNA were significantly higher in adipose tissue, lung and spleen, and adipose tissue exhibited significantly higher levels of ADIPOR2 mRNA followed by the spleen and lung compared with other tissues. 4. Temporal expression profiles of adiponectin, ADIPOR1 and ADIPOR2 mRNA showed gender differences in adipose tissue and skeletal muscle at certain ages. In adipose tissue, adiponectin mRNA was higher in 154-d-old females and ADIPOR1 mRNA was higher in 154-d-old males: Adiponectin and ADIPOR2 mRNA were higher, and ADIPOR1 mRNA was lower, in thigh muscle in female compared with male chickens. 5. The correlation data showed that, except for adiponectin mRNA, the levels of ADIPOR1 and ADIPOR2 mRNA in thigh muscle of males were significantly positively correlated with IMF (r = 0.206 for the ADIPOR1 gene and r = 0.676 for the ADIPOR2 gene). 6. Taken together, it was concluded that adiponectin and the ADIPOR1 and ADIPOR2 genes are ubiquitously expressed in various tissues of Tibetan chicken and the expression of the adiponectin system is gender-dependant at certain ages in adipose tissue and skeletal muscle.

Adiponectin deficiency impairs liver regeneration through attenuating STAT3 phosphorylation in mice.

PubMed

Shu, Run-Zhe; Zhang, Feng; Wang, Fang; Feng, De-Chun; Li, Xi-Hua; Ren, Wei-Hua; Wu, Xiao-Lin; Yang, Xue; Liao, Xiao-Dong; Huang, Lei; Wang, Zhu-Gang

2009-09-01

Liver regeneration is a very complex and well-orchestrated process associated with signaling cascades involving cytokines, growth factors, and metabolic pathways. Adiponectin is an adipocytokine secreted by mature adipocytes, and its receptors are widely distributed in many tissues, including the liver. Adiponectin has direct actions in the liver with prominent roles to improve hepatic insulin sensitivity, increase fatty acid oxidation, and decrease inflammation. To test the hypothesis that adiponectin is required for normal progress of liver regeneration, 2/3 partial hepatectomy (PH) was performed on wild-type and adiponectin-null mice. Compared to wild-type mice, adiponectin-null mice displayed decreased liver mass regrowth, impeded hepatocyte proliferation, and increased hepatic lipid accumulation. Gene expression analysis revealed that adiponectin regulated the gene transcription related to lipid metabolism. Furthermore, the suppressed hepatocyte proliferation was accompanied with reduced signal transducer and activator of transcription protein 3 (STAT3) activity and enhanced suppressor of cytokine signaling 3 (Socs3) transcription. In conclusion, adiponectin-null mice exhibit impaired liver regeneration and increased hepatic steatosis. Increased expression of Socs3 and subsequently reduced activation of STAT3 in adiponectin-null mice may contribute to the alteration of the liver regeneration capability and hepatic lipid metabolism after PH.

The I148M PNPLA3 polymorphism influences serum adiponectin in patients with fatty liver and healthy controls.

PubMed

Valenti, Luca; Rametta, Raffaela; Ruscica, Massimiliano; Dongiovanni, Paola; Steffani, Liliana; Motta, Benedetta Maria; Canavesi, Elena; Fracanzani, Anna Ludovica; Mozzi, Enrico; Roviaro, Giancarlo; Magni, Paolo; Fargion, Silvia

2012-08-16

Reduced adiponectin is implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), and the I148M Patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism predisposes to NAFLD and liver damage progression in NASH and chronic hepatitis C (CHC) by still undefined mechanisms, possibly involving regulation of adipose tissue function. Aim of this study was to evaluate whether the I148M PNPLA3 polymorphism influences serum adiponectin in liver diseases and healthy controls. To this end, we considered 144 consecutive Italian patients with NAFLD, 261 with CHC, 35 severely obese subjects, and 257 healthy controls with very low probability of steatosis, all with complete clinical and genetic characterization, including adiponectin (ADIPOQ) genotype. PNPLA3 rs738409 (I148M) and ADIPOQ genotypes were evaluated by Taqman assays, serum adiponectin by ELISA. Adiponectin mRNA levels were evaluated by quantitative real-time PCR in the visceral adipose tissue (VAT) of 35 obese subjects undergoing bariatric surgery. Adiponectin levels were independently associated with the risk of NAFLD and with the histological severity of the disease. Adiponectin levels decreased with the number of 148 M PNPLA3 alleles at risk of NASH both in patients with NAFLD (p = 0.03), and in healthy subjects (p = 0.04). At multivariate analysis, PNPLA3 148 M alleles were associated with low adiponectin levels (<6 mg/ml, median value) independently of NAFLD diagnosis, age, gender, BMI, and ADIPOQ genotype (OR 1.67, 95% c.i. 1.07-2.1 for each 148 M allele). The p.148 M PNPLA3 variant was associated with decreased adiponectin mRNA levels in the VAT of obese patients (p < 0.05) even in the absence of NASH. In contrast, in CHC, characterized by adiponectin resistance, low adiponectin was associated with male gender and steatosis, but not with PNPLA3 and ADIPOQ genotypes and viral features. The I148M PNPLA3 variant is associated with adiponectin levels in patients with NAFLD and in healthy subjects, but in the presence of adiponectin resistance not in CHC patients. The I148M PNPLA3 genotype may represent a genetic determinant of serum adiponectin levels. Modulation of serum adiponectin might be involved in mediating the susceptibility to steatosis, NASH, and hepatocellular carcinoma in carriers of the 148 M PNPLA3 variant without CHC, with potential therapeutic implications.

Myocardial Adiponectin Isoform Shift in Dogs with Congestive Heart Failure—A Comparison to Hibernating Brown Bears (Ursus arctos horribilis)

PubMed Central

Nelson, O. Lynne; Wood, Rachael M.; Häggström, Jens; Kvart, Clarence; Robbins, Charles T.

2017-01-01

Adiponectin is the most abundant plasma adipokine, and is well known for its role in energy homeostasis and cardiac protection. In humans with dilated cardiomyopathy, myocardial adiponectin protein expression is reduced compared to normal hearts and has been implicated in the pathology of cardiomyopathy. Serum adiponectin levels are often conflicting, with higher levels associated with poor survival in humans with congestive heart failure (CHF). We evaluated adiponectin serum concentrations and myocardial protein expression in dogs with naturally occurring myxomatous mitral valve disease and CHF. We compared the findings to active and hibernating brown bears as bears are adapted to endure an extreme period of low cardiac output during their annual hibernation. Bears exhibited largely the active high-molecular weight (HMW) versus the low-molecular weight isoforms of myocardial adiponectin (HMW:LMW = 6.3) during both the active period and hibernation, while healthy dogs exhibited a more balanced mix of isoforms. Dogs with CHF expressed predominately HMW isoforms of adiponectin (HMW:LMW = 12.5), appearing more similar to bears. In contrast to humans, serum adiponectin was significantly lower in dogs with CHF and lowest levels in the severest CHF class. In both dogs and bears, myocardial adiponectin was expressed independent of circulating adiponectin concentrations, suggesting a local regulatory mechanism within the heart. PMID:29056695

Genetic determination of adiponectin and its relationship with body fat topography in multigenerational families of African heritage.

PubMed

Miljkovic-Gacic, Iva; Wang, Xiaojing; Kammerer, Candace M; Bunker, Clareann H; Wheeler, Victor W; Patrick, Alan L; Kuller, Lewis H; Evans, Rhobert W; Zmuda, Joseph M

2007-02-01

Adiponectin, an adipose-specific protein, is negatively associated with adiposity, insulin sensitivity, and diabetes. Very few studies have examined the role of heredity in the regulation of adiponectin and its association with body fat among individuals of African heritage. Thus, we measured fasting serum adiponectin levels by radioimmunoassay and body composition by dual-energy x-ray absorptiometry (DEXA) in 402 individuals aged 18 to 103 years belonging to 7 multigenerational families of African heritage in the relatively homogeneous island population of Tobago. Heritability of adiponectin was 33.2% (P < .01), and age, sex, and body mass index explained 23.4% of the variance in adiponectin. Sex-specific heritability was significant in men (heritability, 34%; P < .05), but not in women. The inverse associations between body mass index and percentage of body fat and adiponectin, independent of age and height, were much stronger in women (all P values <.001) than in men. However, percentage of trunk fat was consistently strongly associated with adiponectin in both men (r = -0.40, P < .001) and women (r = -0.44, P < .001), independent of age and height. This study suggests that genetic factors are a significant source of interindividual differences in circulating adiponectin among Afro-Caribbeans. Adiponectin may serve as a promising quantitative intermediate trait in studies designed to map the genes underlying diabetes and obesity in this population.

Protein kinase CK2 interacts with adiponectin receptor 1 and participates in adiponectin signaling.

PubMed

Heiker, John T; Wottawah, Cornelia M; Juhl, Cathleen; Kosel, David; Mörl, Karin; Beck-Sickinger, Annette G

2009-06-01

Adiponectin is an adipokine with anti-atherogenic, anti-diabetic and insulin sensitizing properties. Its effects on energy homeostasis, glucose and lipid metabolism are mediated by two ubiquitously expressed seven-transmembrane receptors, AdipoR1 and -R2. With the exception of APPL1 and RACK1, no intracellular binding partners of adiponectin receptors are reported and thus signaling pathways downstream of these receptors remain largely unknown. To incorporate adiponectins protective potential in drug development it is essential to understand adiponectin signaling cascades in detail. A yeast two-hybrid approach employing AdipoR1s cytoplasmatic N-terminus led to the identification of the regulatory subunit of protein kinase CK2. We confirmed the interaction in co-immunoprecipitation, ELISA experiments and co-localization analysis in mammalian cells. Furthermore we could localize the interaction site in an N-terminal basic region close to the transmembrane domain. In adiponectin stimulation experiments of C2C12 mouse myotubes and MCF7 cells incorporating CK2 inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H-benz-imidazole (DMAT) we found a modulator role of CK2 in adiponectin signaling. Accordingly we identified the regulatory subunit of protein kinase CK2 as a novel intracellular partner of AdipoR1 and have strong evidence of CK2 as an effector molecule in adiponectin signaling. Since CK2 is involved in signaling cascades of other adipokines and hormones, e.g. leptin and insulin, our findings suggest a possible key function in crosstalk between adiponectin and insulin signaling pathways and could provide further insight into the anti-diabetic effects of adiponectin.

Knockout maternal adiponectin increases fetal growth in mice: potential role for trophoblast IGFBP-1.

PubMed

Qiao, Liping; Wattez, Jean-Sebastien; Lee, Samuel; Guo, Zhuyu; Schaack, Jerome; Hay, William W; Zita, Matteo Moretto; Parast, Mana; Shao, Jianhua

2016-11-01

The main objective of this study was to investigate whether maternal adiponectin regulates fetal growth through the endocrine system in the fetal compartment. Adiponectin knockout (Adipoq (-/-) ) mice and in vivo adenovirus-mediated reconstitution were used to study the regulatory effect of maternal adiponectin on fetal growth. Primary human trophoblast cells were treated with adiponectin and a specific peroxisome proliferator-activated receptor α (PPARα) agonist or antagonist to study the underlying mechanism through which adiponectin regulates fetal growth. The body weight of fetuses from Adipoq (-/-) dams was significantly greater than that of wild-type dams at both embryonic day (E)14.5 and E18.5. Adenoviral vector-mediated maternal adiponectin reconstitution attenuated the increased fetal body weight induced by maternal adiponectin deficiency. Significantly increased blood glucose, triacylglycerol and NEFA levels were observed in Adipoq (-/-) dams, suggesting that nutrient supply contributes to maternal adiponectin-regulated fetal growth. Although fetal blood IGF-1 concentrations were comparable in fetuses from Adipoq (-/-) and wild-type dams, remarkably low levels of IGF-binding protein 1 (IGFBP-1) were observed in the serum of fetuses from Adipoq (-/-) dams. IGFBP-1 was identified in the trophoblast cells of human and mouse placentas. Maternal fasting robustly increased IGFBP-1 levels in mouse placentas, while reducing fetal weight. Significantly low IGFBP-1 levels were found in placentas of Adipoq (-/-) dams. Adiponectin treatment increased IGFBP-1 levels in primary cultured human trophoblast cells, while the PPARα antagonist, MK886, abolished this stimulatory effect. These results indicate that, in addition to nutrient supply, maternal adiponectin inhibits fetal growth by increasing IGFBP-1 expression in trophoblast cells.

Clinical characteristics of high plasma adiponectin and high plasma leptin as risk factors for arterial stiffness and related end-organ damage.

PubMed

Kohara, Katsuhiko; Ochi, Masayuki; Okada, Yoko; Yamashita, Taiji; Ohara, Maya; Kato, Takeaki; Nagai, Tokihisa; Tabara, Yasuharu; Igase, Michiya; Miki, Tetsuro

2014-08-01

The relationship between plasma levels of adiponectin and cardiovascular events is inconclusive. We evaluated the clinical characteristics of people with high plasma adiponectin and high plasma leptin levels. Thousand seven hundred participants recruited from visitors to the Anti-Aging Doc were divided into four groups by combining the bipartiles of plasma adiponectin and leptin levels in men and women separately: AL, high adiponectin and high leptin; Al, high adiponectin and low leptin; al, low adiponectin and low leptin; aL, low adiponectin and high leptin. Body composition, including visceral fat area and thigh muscle cross-sectional area (CSA), brachial-ankle pulse wave velocity (baPWV), periventricular hyperintensity, and urinary albumin excretion, were determined. Twenty percent of the studied population fell within the AL group. This group had a significantly higher visceral fat area than the Al group. Thigh muscle CSA was lowest in the AL group among groups. baPWV, brain white matter lesions, and albuminuria findings in the AL group were significantly higher than those of the Al group. Multiple and logistic regression analyses with confounding parameters further confirmed that plasma adiponectin was not an independent determinant for brain and renal small vessel-related disease. These findings suggest that the plasma level of adiponectin alone is not enough for the risk stratification of cardiovascular disease. Leptin resistance associated with skeletal muscle loss in addition to obesity may need to be addressed to identify high risk people with high plasma adiponectin levels. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Human milk adiponectin is associated with infant growth in two independent cohorts.

PubMed

Woo, Jessica G; Guerrero, M Lourdes; Altaye, Mekibib; Ruiz-Palacios, Guillermo M; Martin, Lisa J; Dubert-Ferrandon, Alix; Newburg, David S; Morrow, Ardythe L

2009-06-01

Adiponectin, a circulating adipocyte protein, is associated with lower obesity. We have previously shown that adiponectin is present in human milk. This study determined whether higher milk adiponectin is associated with infant growth and investigated milk adiponectin's oligomeric form. This is a study of two parallel longitudinal cohorts of breastfed infants born between 1998 and 2005. Forty-five mother-infant pairs from Cincinnati, OH and 277 mother-infant pairs from Mexico City, Mexico were analyzed. All participants were healthy, term infants breastfed at least 1 month who completed 6 months of follow-up. Monthly milk samples (n = 1,379) up to 6 months were assayed for adiponectin by radioimmunoassay. Infant weight-for-age, length-for-age, and weight-for-length Z-scores up to 6 months of age were calculated using World Health Organization standards. Repeated-measures analysis was conducted. The structural form of human milk adiponectin was assessed by western blot. In the population studies, initial milk adiponectin was 24.0 +/- 8.6 microg/L and did not differ by cohort. Over the first 6 months, higher milk adiponectin was associated with lower infant weight-for-age Z-score (-0.20 +/- 0.04, p < 0.0001) and weight-for-length Z-score (-0.29 +/- 0.08, p = 0.0002) but not length-for-age Z-score, adjusted for covariates, with no difference by cohort. By western blot, human milk adiponectin was predominantly in the biologically active high-molecular-weight form. Our data suggest milk adiponectin may play a role in the early growth and development of breastfed infants.

Globular Adiponectin, Acting via AdipoR1/APPL1, Protects H9c2 Cells from Hypoxia/Reoxygenation-Induced Apoptosis

PubMed Central

Park, Min; Youn, ByungSoo; Zheng, Xi-long; Wu, Donghai; Xu, Aimin; Sweeney, Gary

2011-01-01

Cardiomyocyte apoptosis is an important remodeling event contributing to heart failure and adiponectin may mediate cardioprotective effects at least in part via attenuating apoptosis. Here we used hypoxia-reoxygenation (H/R) induced apoptosis in H9c2 cells to examine the effect of adiponectin and cellular mechanisms of action. We first used TUNEL labeling in combination with laser scanning cytometry to demonstrate that adiponectin prevented H/R-induced DNA fragmentation. The anti-apoptotic effect of adiponectin was also verified via attenuation of H/R-induced phosphatidylserine exposure using annexin V binding. H/R-induced apoptosis via the mitochondrial-mediated intrinsic pathway of apoptosis as assessed by cytochrome c release into cytosol and caspase-3 activation, both of which were attenuated by adiponectin. Mechanistically, we demonstrated that adiponectin enhanced anti-oxidative potential in these cells which led to attenuation of the increase in intracellular reactive oxygen species (ROS) caused by H/R. To further address the mechanism of adiponctins anti-apoptotic effects we used siRNA to efficiently knockdown adiponectin receptor (AdipoR1) expression and found that this attenuated the protective effects of adiponectin on ROS production and caspase 3 activity. Knockdown of APPL1, an important intracellular binding partner for AdipoR, also significantly reduced the ability of adiponectin to prevent H/R-induced ROS generation and caspase 3 activity. In summary, H/R-induced ROS generation and activation of the intrinsic apoptotic pathway was prevented by adiponectin via AdipoR1/APPL1 signaling and increased anti-oxidant potential. PMID:21552570

Circadian expression of adiponectin and its receptors in human adipose tissue

USDA-ARS?s Scientific Manuscript database

Adiponectin is one of the most clinically relevant cytokines associated with obesity. However, circadian rhythmicity of adiponectin in human adipose tissue (AT) has not been analyzed. To assess whether the mRNA levels of adiponectin and its receptors (ADIPOR1 and ADIPOR2) might show daily circadian ...

Implications of adiponectin in linking metabolism to testicular function.

PubMed

Martin, Luc J

2014-05-01

Obesity is a major health problem, contributing to the development of various diseases with aging. In humans, obesity has been associated with reduced testosterone production and subfertility. Adipose tissue is an important source of hormones having influences on both metabolism and reproduction. Among them, the production and secretion of adiponectin is inversely correlated to the severity of obesity. The purpose of this review of literature is to present the current state of knowledge on adiponectin research to determine whether this hormone affects reproduction in men. Surprisingly, evidences show negative influences of adiponectin on GnRH secretion from the hypothalamus, LH and FSH secretion from the pituitary and testosterone at the testicular level. Thus far, the involvement of adiponectin in the influence of metabolism on reproduction in men is limited. However, adiponectin and its receptors are expressed by different cell types of the male gonad, including Leydig cells, spermatozoa, and epididymis. In addition, actions of adiponectin at the testicular level have been shown to promote spermatogenesis and sperm maturation. Therefore, autocrine/paracrine actions of adiponectin in the testis may contribute to support male reproductive function.

Maternal docosahexaenoic acid increases adiponectin and normalizes IUGR-induced changes in rat adipose deposition.

PubMed

Bagley, Heidi N; Wang, Yan; Campbell, Michael S; Yu, Xing; Lane, Robert H; Joss-Moore, Lisa A

2013-01-01

Intrauterine growth restriction (IUGR) predisposes to obesity and adipose dysfunction. We previously demonstrated IUGR-induced increased visceral adipose deposition and dysregulated expression of peroxisome proliferator activated receptor- γ 2 (PPAR γ 2) in male adolescent rats, prior to the onset of obesity. In other studies, activation of PPAR γ increases subcutaneous adiponectin expression and normalizes visceral adipose deposition. We hypothesized that maternal supplementation with docosahexaenoic acid (DHA), a PPAR γ agonist, would normalize IUGR adipose deposition in association with increased PPAR γ , adiponectin, and adiponectin receptor expression in subcutaneous adipose. To test these hypotheses, we used a well-characterized model of uteroplacental-insufficiency-(UPI-) induced IUGR in the rat with maternal DHA supplementation. Our primary findings were that maternal DHA supplementation during rat pregnancy and lactation (1) normalizes IUGR-induced changes in adipose deposition and visceral PPAR γ expression in male rats and (2) increases serum adiponectin, as well as adipose expression of adiponectin and adiponectin receptors in former IUGR rats. Our novel findings suggest that maternal DHA supplementation may normalize adipose dysfunction and promote adiponectin-induced improvements in metabolic function in IUGR.

Expression of FABP4, adipsin and adiponectin in Paneth cells is modulated by gut Lactobacillus.

PubMed

Su, Xiaomin; Yan, Hui; Huang, Yugang; Yun, Huan; Zeng, Benhua; Wang, Enlin; Liu, Yu; Zhang, Yuan; Liu, Feifei; Che, Yongzhe; Zhang, Zhiqian; Yang, Rongcun

2015-12-21

We here found that intestinal epithelial Paneth cells secrete FABP4, adipsin and adiponectin in both mice and human. Deletion of Paneth cell results in the decrease of FABP4, adipsin and adiponectin not only in intestinal crypt cells but also in sera, suggesting that they may influence the state of the whole body. We also demonstrate that expression of FABP4, adipsin and adiponectin may be modulated by specific gut microbiota. In germ-free (GF) mice, the expression of FABP4, adipsin and adiponectin were lower or difficult to be detected. Feces transplantation promoted the expression of FABP4, adipsin and adiponectin in gut epithelial Paneth cells. We have found that Lactobacillus NK6 colony, which has the highest similarity with Lactobacillus taiwanensis strain BCRC 17755, may induce the expression of FABP4, adipsin and adiponectin through TRAF2 and TRAF6 ubiquitination mediated NF-κB signaling. Taken together, our findings set up a novel mechanism for FABP4, adipsin and adiponectin through gut microbiota mediating expression in gut Paneth cells.

Expression of FABP4, adipsin and adiponectin in Paneth cells is modulated by gut Lactobacillus

PubMed Central

Su, Xiaomin; Yan, Hui; Huang, Yugang; Yun, Huan; Zeng, Benhua; Wang, Enlin; Liu, Yu; Zhang, Yuan; Liu, Feifei; Che, Yongzhe; Zhang, Zhiqian; Yang, Rongcun

2015-01-01

We here found that intestinal epithelial Paneth cells secrete FABP4, adipsin and adiponectin in both mice and human. Deletion of Paneth cell results in the decrease of FABP4, adipsin and adiponectin not only in intestinal crypt cells but also in sera, suggesting that they may influence the state of the whole body. We also demonstrate that expression of FABP4, adipsin and adiponectin may be modulated by specific gut microbiota. In germ-free (GF) mice, the expression of FABP4, adipsin and adiponectin were lower or difficult to be detected. Feces transplantation promoted the expression of FABP4, adipsin and adiponectin in gut epithelial Paneth cells. We have found that Lactobacillus NK6 colony, which has the highest similarity with Lactobacillus taiwanensis strain BCRC 17755, may induce the expression of FABP4, adipsin and adiponectin through TRAF2 and TRAF6 ubiquitination mediated NF-κB signaling. Taken together, our findings set up a novel mechanism for FABP4, adipsin and adiponectin through gut microbiota mediating expression in gut Paneth cells. PMID:26687459

Adiponectin promotes VEGF-A-dependent angiogenesis in human chondrosarcoma through PI3K, Akt, mTOR, and HIF-α pathway.

PubMed

Lee, Hsiang-Ping; Lin, Chih-Yang; Shih, Jhao-Sheng; Fong, Yi-Chin; Wang, Shih-Wei; Li, Te-Mao; Tang, Chih-Hsin

2015-11-03

Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. On the other hand, angiogenesis is a critical step in tumor growth and metastasis. However, the relationship of adiponectin with vascular endothelial growth factor-A (VEGF-A) expression and angiogenesis in human chondrosarcoma is mostly unknown. In this study we first demonstrated that the expression of adiponectin was correlated with tumor stage of human chondrosarcoma tissues. In addition, we also found that adiponectin increased VEGF-A expression in human chondrosarcoma cells and subsequently induced migration and tube formation in human endothelial progenitor cells (EPCs). Adiponectin promoted VEGF-A expression through adiponectin receptor (AdipoR), phosphoinositide 3 kinase (PI3K), Akt, mammalian target of rapamycin (mTOR), and hypoxia-inducible factor-1α (HIF)-1α signaling cascades. Knockdown of adiponectin decreased VEGF-A expression and also abolished chondrosarcoma conditional medium-mediated tube formation in EPCs in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and Matrigel plug nude mice model in vivo. Therefore, adiponectin is crucial for tumor angiogenesis and growth, which may represent a novel target for anti-angiogenic therapy in human chondrosarcoma.

Adiponectin promotes VEGF-A-dependent angiogenesis in human chondrosarcoma through PI3K, Akt, mTOR, and HIF-α pathway

PubMed Central

Shih, Jhao-Sheng; Fong, Yi-Chin; Wang, Shih-Wei; Li, Te-Mao; Tang, Chih-Hsin

2015-01-01

Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. On the other hand, angiogenesis is a critical step in tumor growth and metastasis. However, the relationship of adiponectin with vascular endothelial growth factor-A (VEGF-A) expression and angiogenesis in human chondrosarcoma is mostly unknown. In this study we first demonstrated that the expression of adiponectin was correlated with tumor stage of human chondrosarcoma tissues. In addition, we also found that adiponectin increased VEGF-A expression in human chondrosarcoma cells and subsequently induced migration and tube formation in human endothelial progenitor cells (EPCs). Adiponectin promoted VEGF-A expression through adiponectin receptor (AdipoR), phosphoinositide 3 kinase (PI3K), Akt, mammalian target of rapamycin (mTOR), and hypoxia-inducible factor-1α (HIF)-1α signaling cascades. Knockdown of adiponectin decreased VEGF-A expression and also abolished chondrosarcoma conditional medium-mediated tube formation in EPCs in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and Matrigel plug nude mice model in vivo. Therefore, adiponectin is crucial for tumor angiogenesis and growth, which may represent a novel target for anti-angiogenic therapy in human chondrosarcoma. PMID:26468982

Longitudinal Analysis of Adiponectin through 20-Year Type 1 Diabetes Duration

PubMed Central

LeCaire, Tamara J.; Palta, Mari

2015-01-01

Little information exists on the trajectory and determinants of adiponectin, a possible insulin sensitizer and marker for inflammation and endothelial function, across the duration of type 1 diabetes. The Wisconsin Diabetes Registry Study followed an incident cohort ≤30 years of age when diagnosed with type 1 diabetes during 1987–1992 up to 20-year duration. Adiponectin was concurrently and retrospectively (from samples frozen at −80°C) measured for those participating in a 20-year exam (n = 304), during 2007–2011. Adiponectin levels were higher in females, declined through adolescence, and increased with age thereafter. Lower levels were associated with greater body weight and waist circumference and with higher insulin dose, especially at longer diabetes durations. Higher levels were associated with higher HbA1c and, at longer durations, with higher albumin-creatinine ratio. Adiponectin levels showed consistency within individuals that was not explained by these factors. We conclude that markers for insulin resistance are associated with lower adiponectin, and markers for potential microvascular complications are associated with higher adiponectin. The previously reported relationship with HbA1c remains largely unexplained. Additional individual specific factors likely also influence adiponectin level. The relationship between adiponectin and urinary protein excretion may enable identification of those predisposed to kidney disease earlier in type 1 diabetes. PMID:25950008

Longitudinal Analysis of Adiponectin through 20-Year Type 1 Diabetes Duration.

PubMed

LeCaire, Tamara J; Palta, Mari

2015-01-01

Little information exists on the trajectory and determinants of adiponectin, a possible insulin sensitizer and marker for inflammation and endothelial function, across the duration of type 1 diabetes. The Wisconsin Diabetes Registry Study followed an incident cohort ≤ 30 years of age when diagnosed with type 1 diabetes during 1987-1992 up to 20-year duration. Adiponectin was concurrently and retrospectively (from samples frozen at -80 °C) measured for those participating in a 20-year exam (n = 304), during 2007-2011. Adiponectin levels were higher in females, declined through adolescence, and increased with age thereafter. Lower levels were associated with greater body weight and waist circumference and with higher insulin dose, especially at longer diabetes durations. Higher levels were associated with higher HbA1c and, at longer durations, with higher albumin-creatinine ratio. Adiponectin levels showed consistency within individuals that was not explained by these factors. We conclude that markers for insulin resistance are associated with lower adiponectin, and markers for potential microvascular complications are associated with higher adiponectin. The previously reported relationship with HbA1c remains largely unexplained. Additional individual specific factors likely also influence adiponectin level. The relationship between adiponectin and urinary protein excretion may enable identification of those predisposed to kidney disease earlier in type 1 diabetes.

Adiponectin in Fresh Frozen Plasma Contributes to Restoration of Vascular Barrier Function after Hemorrhagic Shock

PubMed Central

Huby, Maria P.; Duan, Chaojun; Baer, Lisa; Peng, Zhanglong; Kozar, Rosemary A.; Doursout, Marie-Francoise; Holcomb, John B.; Wade, Charles E.; Ko, Tien C.

2015-01-01

Hemorrhagic shock is the leading cause of preventable deaths in civilian and military trauma. Use of fresh frozen plasma (FFP) in patients requiring massive transfusion is associated with improved outcomes. FFP contains significant amounts of adiponectin, which is known to have vascular protective function. We hypothesize that FFP improves vascular barrier function largely via adiponectin. Plasma adiponectin levels were measured in 19 severely injured patients in hemorrhagic shock (HS). Compared to normal individuals, plasma adiponectin levels decreased to 49% in HS patients prior to resuscitation (p<0.05) and increased to 64% post resuscitation (but not significant). In a HS mouse model, we demonstrated a similar decrease in plasma adiponectin to 54% but a significant increase to 79% by FFP resuscitation compared to baseline (p<0.05). HS disrupted lung vascular barrier function, leading to an increase in permeability. FFP resuscitation reversed these HS-induced effects. Immunodepletion of adiponectin from FFP abolished FFP's effects on blocking endothelial hyperpermeability in vitro, and on improving lung vascular barrier function in HS mice. Replenishment with adiponectin rescued FFP's effects. These findings suggest that adiponectin is an important component in FFP resuscitation contributing to the beneficial effects on vascular barrier function after HS. PMID:26263440

Metabolic Profiling of Adiponectin Levels in Adults: Mendelian Randomization Analysis.

PubMed

Borges, Maria Carolina; Barros, Aluísio J D; Ferreira, Diana L Santos; Casas, Juan Pablo; Horta, Bernardo Lessa; Kivimaki, Mika; Kumari, Meena; Menon, Usha; Gaunt, Tom R; Ben-Shlomo, Yoav; Freitas, Deise F; Oliveira, Isabel O; Gentry-Maharaj, Aleksandra; Fourkala, Evangelia; Lawlor, Debbie A; Hingorani, Aroon D

2017-12-01

Adiponectin, a circulating adipocyte-derived protein, has insulin-sensitizing, anti-inflammatory, antiatherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin in humans are unknown. Our aims were to define the metabolic profile associated with higher blood adiponectin concentration and investigate whether variation in adiponectin concentration affects the systemic metabolic profile. We applied multivariable regression in ≤5909 adults and Mendelian randomization (using cis -acting genetic variants in the vicinity of the adiponectin gene as instrumental variables) for analyzing the causal effect of adiponectin in the metabolic profile of ≤37 545 adults. Participants were largely European from 6 longitudinal studies and 1 genome-wide association consortium. In the multivariable regression analyses, higher circulating adiponectin was associated with higher high-density lipoprotein lipids and lower very-low-density lipoprotein lipids, glucose levels, branched-chain amino acids, and inflammatory markers. However, these findings were not supported by Mendelian randomization analyses for most metabolites. Findings were consistent between sexes and after excluding high-risk groups (defined by age and occurrence of previous cardiovascular event) and 1 study with admixed population. Our findings indicate that blood adiponectin concentration is more likely to be an epiphenomenon in the context of metabolic disease than a key determinant. © 2017 The Authors.

Adiponectin regulates albuminuria and podocyte function in mice

PubMed Central

Sharma, Kumar; RamachandraRao, Satish; Qiu, Gang; Usui, Hitomi Kataoka; Zhu, Yanqing; Dunn, Stephen R.; Ouedraogo, Raogo; Hough, Kelly; McCue, Peter; Chan, Lawrence; Falkner, Bonita; Goldstein, Barry J.

2008-01-01

Increased albuminuria is associated with obesity and diabetes and is a risk factor for cardiovascular and renal disease. However, the link between early albuminuria and adiposity remains unclear. To determine whether adiponectin, an adipocyte-derived hormone, is a communication signal between adipocytes and the kidney, we performed studies in a cohort of patients at high risk for diabetes and kidney disease as well as in adiponectin-knockout (Ad–/–) mice. Albuminuria had a negative correlation with plasma adiponectin in obese patients, and Ad–/– mice exhibited increased albuminuria and fusion of podocyte foot processes. In cultured podocytes, adiponectin administration was associated with increased activity of AMPK, and both adiponectin and AMPK activation reduced podocyte permeability to albumin and podocyte dysfunction, as evidenced by zona occludens–1 translocation to the membrane. These effects seemed to be caused by reduction of oxidative stress, as adiponectin and AMPK activation both reduced protein levels of the NADPH oxidase Nox4 in podocytes. Ad–/– mice treated with adiponectin exhibited normalization of albuminuria, improvement of podocyte foot process effacement, increased glomerular AMPK activation, and reduced urinary and glomerular markers of oxidant stress. These results suggest that adiponectin is a key regulator of albuminuria, likely acting through the AMPK pathway to modulate oxidant stress in podocytes. PMID:18431508

APPL1-mediated activation of STAT3 contributes to inhibitory effect of adiponectin on hepatic gluconeogenesis.

PubMed

Ding, Youming; Zhang, Deling; Wang, Bin; Zhang, Yemin; Wang, Lei; Chen, Xiaoyan; Li, Mingxin; Tang, Zhao; Wang, Changhua

2016-09-15

Adiponectin has been shown to suppress hepatic gluconeogenesis. However, the signaling pathways underlying its action remain ill-defined. The purpose of this study was to examine the potential role of APPL1 in mediating anti-gluconeogenic ability of adiponectin. Primary hepatocytes were isolated from male C57BL/6 mice. Western blot and RT-PCR were performed to detect protein expression and mRNA level, respectively. The protein-protein association was determined by immunoprecipitation and GST pull-down assay. We found that APPL1 protein levels were negatively associated with expressions of proteins and mRNAs of gluconeogenesis enzymes under stimulation with adiponectin. In addition, adiponectin-stimulated STAT3 phosphorylation and acetylation were positively regulated by APPL1 and negative regulated by SirT1. Pharmacological and genetic inhibition of STAT3 mitigated impact of adiponectin on hepatic gluconeogenesis. Furthermore, adiponectin administration facilitated the binding of APPL1 to SirT1 and suppressed the association of SirT1 with STAT3. Taken together, our study showed that APPL1-SirT1-STAT3 pathway mediated adiponectin signaling in primary hepatocytes. This new finding provides a novel mechanism by which adiponectin suppresses hepatic gluconeogenesis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Plasma Adiponectin Does Not Correlate With Insulin Resistance and Cardiometabolic Variables in Nondiabetic Asian Indian Teenagers

PubMed Central

Snehalatha, Chamukuttan; Yamuna, Annasami; Ramachandran, Ambady

2008-01-01

OBJECTIVE—The objectives of this study were to determine age- and sex-specific concentrations of adiponectin in Asian Indian teenagers and adults and to assess whether its blood levels correlated with insulin resistance and other cardiometabolic parameters. RESEARCH DESIGN AND METHODS—We studied 196 teenagers (94 boys, 102 girls) 12–18 years of age, selected from a cohort of 2,640 individuals from a cross-sectional school-based survey in Chennai, India. For comparison, adiponectin and plasma insulin were measured in 84 healthy adults. Correlation of adiponectin with plasma levels of insulin, proinsulin, insulin resistance, anthropometry, and family history of diabetes were studied. RESULTS—Adiponectin showed a sex dimorphism, with girls having higher values (in μg/ml) (10.3 ± 5.0) than boys (8.4 ± 3.5) (P < 0.0001), and it showed a positive correlation with HDL cholesterol in boys only and not with other lipid parameters, insulin resistance, proinsulin, anthropometry, and family history of diabetes. In the adults, adiponectin correlated with fasting glucose and inversely with triglycerides. CONCLUSIONS—In Asian Indian adults and teenagers, adiponectin did not correlate directly with measures of insulin sensitivity, overweight, and other cardiometabolic variables. This was at variance with several reports in other populations showing an inverse association of adiponectin with insulin resistance, proinsulin, and BMI, suggesting ethnic differences in the relationship of adiponectin with insulin sensitivity. The role of adiponectin in relation to action of insulin needs more detailed studies in Asian Indians. PMID:18809626

Exercise improves adiponectin concentrations irrespective of the adiponectin gene polymorphisms SNP45 and the SNP276 in obese Korean women.

PubMed

Lee, Kyoung-Young; Kang, Hyun-Sik; Shin, Yun-A

2013-03-10

The effects of exercise on adiponectin levels have been reported to be variable and may be attributable to an interaction between environmental and genetic factors. The single nucleotide polymorphisms (SNP) 45 (T>G) and SNP276 (G>T) of the adiponectin gene are associated with metabolic risk factors including adiponectin levels. We examined whether SNP45 and SNP276 would differentially influence the effect of exercise training in middle-aged women with uncomplicated obesity. We conducted a prospective study in the general community that included 90 Korean women (age 47.0±5.1 years) with uncomplicated obesity. The intervention was aerobic exercise training for 3 months. Body composition, adiponectin levels, and other metabolic risk factors were measured. Prior to exercise training, only body weight differed among the SNP276 genotypes. Exercise training improved body composition, systolic blood pressure, maximal oxygen consumption, high-density lipoprotein cholesterol, and leptin levels. In addition, exercise improved adiponectin levels irrespective of weight gain or loss. However, after adjustments for age, BMI, body fat (%), and waist circumference, no differences were found in obesity-related characteristics (e.g., adiponectin) following exercise training among the SNP45 and the 276 genotypes. Our findings suggest that aerobic exercise affects adiponectin levels regardless of weight loss and this effect would not be influenced by SNP45 and SNP276 in the adiponectin gene. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Role of adiponectin in delayed embryonic development of the short-nosed fruit bat, Cynopterus sphinx.

PubMed

Anuradha; Krishna, Amitabh

2014-12-01

The aim of this study was to evaluate the role of adiponectin in the delayed embryonic development of Cynopterus sphinx. Adiponectin receptor (ADIPOR1) abundance was first observed to be lower during the delayed versus non-delayed periods of utero-embryonic unit development. The effects of adiponectin treatment on embryonic development were then evaluated during the period of delayed development. Exogenous treatment increased the in vivo rate of embryonic development, as indicated by an increase in weight, ADIPOR1 levels in the utero-embryonic unit, and histological changes in embryonic development. Treatment with adiponectin during embryonic diapause showed a significant increase in circulating progesterone and estradiol concentrations, and in production of their receptors in the utero-embryonic unit. The adiponectin-induced increase in estradiol synthesis was correlated with increased cell survival (BCL2 protein levels) and cell proliferation (PCNA protein levels) in the utero-embryonic unit, suggesting an indirect effect of adiponectin via estradiol synthesis by the ovary. An in vitro study further confirmed the in vivo findings that adiponectin treatment increases PCNA levels together with increased uptake of glucose by increasing the abundance of glucose transporter 8 (GLUT8) in the utero-embryonic unit. The in vitro study also revealed that adiponectin, together with estradiol but not alone, significantly increased ADIPOR1 protein levels. Thus, adiponectin works in concert with estradiol to increase glucose transport to the utero-embryonic unit and promote cell proliferation, which together accelerate embryonic development. © 2014 Wiley Periodicals, Inc.

Ascofuranone stimulates expression of adiponectin and peroxisome proliferator activated receptor through the modulation of mitogen activated protein kinase family members in 3T3-L1, murine pre-adipocyte cell line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Young-Chae, E-mail: ycchang@cu.ac.kr; Cho, Hyun-Ji, E-mail: hjcho.dr@gmail.com

2012-06-08

Highlights: Black-Right-Pointing-Pointer Ascofuranone increases expression of adiponectin and PPAR{gamma}. Black-Right-Pointing-Pointer Inhibitors for MEK and JNK increased the expression of adiponectin and PPAR{gamma}. Black-Right-Pointing-Pointer Ascofuranone significantly suppressed phosho-ERK, while increasing phospho-p38. -- Abstract: Ascofuranone, an isoprenoid antibiotic, was originally isolated as a hypolipidemic substance from a culture broth of the phytopathogenic fungus, Ascochyta visiae. Adiponectin is mainly synthesized by adipocytes. It relieves insulin resistance by decreasing the plasma triglycerides and improving glucose uptake, and has anti-atherogenic properties. Here, we found that ascofuranone increases expression of adiponectin and PPAR{gamma}, a major transcription factor for adiponectin, in 3T3-L1, murine pre-adipocytes cell line, withoutmore » promoting accumulation of lipid droplets. Ascofuranone induced expression of adiponectin, and increases the promoter activity of adiponectin and PPRE, PPAR response element, as comparably as a PPAR{gamma} agonist, rosiglitazone, that stimulates lipid accumulation in the preadipocyte cell line. Moreover, inhibitors for MEK and JNK, like ascofuranone, considerably increased the expression of adiponectin and PPAR{gamma}, while a p38 inhibitor significantly suppressed. Ascofuranone significantly suppressed ERK phosphorylation, while increasing p38 phosphorylation, during adipocyte differentiation program. These results suggest that ascofuranone regulates the expression of adiponectin and PPAR{gamma} through the modulation of MAP kinase family members.« less

Serum adiponectin is increased in advancing liver fibrosis and declines with reduction in fibrosis in chronic hepatitis B.

PubMed

Hui, Chee-Kin; Zhang, Hai-Ying; Lee, Nikki P; Chan, Weng; Yueng, Yui-Hung; Leung, Kar-Wai; Lu, Lei; Leung, Nancy; Lo, Chung-Mau; Fan, Sheung-Tat; Luk, John M; Xu, Aimin; Lam, Karen S; Kwong, Yok-Lam; Lau, George K K

2007-08-01

Despite the possible role of adiponectin in the pathogenesis of liver cirrhosis, few data have been collected from patients in different stages of liver fibrosis. We studied the role of adiponectin in 2 chronic hepatitis B (CHB)-patient cohorts. Serum adiponectin was quantified by enzyme-linked immunosorbent assay. One-hundred liver biopsy specimens from CHB patients with different stages of fibrosis and 38 paired liver biopsies from hepatitis B e antigen-positive patients randomized to lamivudine (n=15), pegylated interferon alfa-2a (n=15) or pegylated interferon alfa-2a plus lamivudine (n=8) therapy for 48 weeks were assessed. Serum adiponectin was detected at levels ranging over fourfold magnitude with advancing fibrosis stage and correlated positively with fibrosis stage [r=0.45, p<0.001]. CHB patients with stage 0-1 fibrosis had higher composition of high molecular weight (HMW) form of adiponectin when compared with CHB patients with liver cirrhosis [mean+/-SEM 51.2+/-2.1% vs. 40.9+/-1.7%, respectively, p=0.001]. After antiviral therapy, patients with fibrosis reduction had marked decline in serum adiponectin level and increase in HMW form of adiponectin [mean+/-SEM 43.5+/-1.2% vs. 37.0+/-3.0%, respectively, p=0.04]. Serum adiponectin may have a role in fibrosis progression in CHB infection. A marked decline in serum adiponectin after antiviral therapy is associated with fibrosis reduction.

The influence of sex, body composition, and nonesterified fatty acids on serum adipokine concentrations.

PubMed

Plaisance, Eric P; Grandjean, Peter W; Judd, Robert L; Jones, Kathy W; Taylor, J Kyle

2009-11-01

Serum adiponectin concentrations are higher in women than men. The sexual dimorphism for adiponectin has been attributed to the direct effects of testosterone on adipose tissue adiponectin secretion. However, serum testosterone and adiponectin concentrations are generally lower in obese men than lean men, suggesting that sex steroids may not be the only factor that contributes to sex differences in serum adiponectin. The primary objective of this study was to examine the influence of sex, body composition, and nonesterified fatty acids (NEFAs) on serum adiponectin concentrations. Women and men between the ages of 18 and 35 years were consecutively accrued into the study. Sixty-one participants were partitioned into normal-weight (15 female and 16 male) or obese (14 female and 16 male) groups. Blood samples were obtained after a 12-hour fast. Differences between groups were determined by analysis of variance with Tukey-Kramer post hoc testing. Serum adiponectin was 26% higher in women compared with men. Body mass index was associated with total serum adiponectin in men (r = -0.63, P < .05) but not women. Adiponectin was correlated with the homeostasis model assessment index in women (r = -0.56, P < .05) and men (r = -0.58, P < .05) and with NEFAs (r = -0.68, P < .05) in men only. After partitioning men and women into normal-weight and obese groups, serum adiponectin was lower and NEFAs were higher in obese men only. Homeostasis model assessment was similar between obese women and men despite higher NEFAs in the obese men. Leptin and plasminogen activator inhibitor-1 were higher in obese participants but were not associated with serum NEFAs. These results suggest that serum NEFAs may reduce adiponectin concentrations independent of their effects on insulin sensitivity in obese young men.

Elevated total plasma-adiponectin is stable over time in young women with bulimia nervosa.

PubMed

Syk, M; Ramklint, M; Fredriksson, R; Ekselius, L; Cunningham, J L

2017-03-01

Bulimia nervosa (BN) is characterized by dysregulated eating behaviour and present data suggest adipokines may regulate food intake. We investigated a possible association between BN and adipokine levels and hypothesized that plasma (P)-adiponectin would be elevated and P-leptin and P-leptin-adiponectin-ratio would be reduced in women with BN. The study was designed as a cross-sectional study with a longitudinal arm for patients with BN. Plasma-adiponectin and leptin was measured in 148 female patients seeking psychiatric ambulatory care and 45 female controls. Fifteen patients were diagnosed with BN and the remaining with other affective and anxiety disorders. P-adiponectin and P-leptin levels were compared between patients with BN, patients without BN and controls. At follow-up 1-2years later, adipokines were reassessed in patients with BN and the Eating Disorder Examination Questionnaire was used to assess symptom severity. P-adiponectin was elevated in patients with BN at baseline and at follow-up when compared to patients without BN and controls (P<0.004 and <0.008 respectively). The difference remained significant after controlling for body mass index. P-adiponectin was correlated to symptom severity at follow-up in patients with BN without morbid obesity (ρ=0.72, P<0.04). P-leptin-adiponectin-ratio was significantly lower in patients with BN compared to controls (P<0.04) and P-leptin non-significantly lower. Findings indicate a stable elevation of P-adiponectin in women with BN. P-adiponectin at follow-up correlates to eating disorder symptom severity in patients without morbid obesity, indicating that P-adiponectin should be further investigated as a possible potential prognostic biomarker for BN. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Adiponectin gene therapy ameliorates high-fat, high-sucrose diet-induced metabolic perturbations in mice

PubMed Central

Kandasamy, A D; Sung, M M; Boisvenue, J J; Barr, A J; Dyck, J R B

2012-01-01

Background and Design: Adiponectin is an adipokine secreted primarily from adipose tissue that can influence circulating plasma glucose and lipid levels through multiple mechanisms involving a variety of organs. In humans, reduced plasma adiponectin levels induced by obesity are associated with insulin resistance and type 2 diabetes, suggesting that low adiponectin levels may contribute the pathogenesis of obesity-related insulin resistance. Methods and Results: The objective of the present study was to investigate whether gene therapy designed to elevate circulating adiponectin levels is a viable strategy for ameliorating insulin resistance in mice fed a high-fat, high-sucrose (HFHS) diet. Electroporation-mediated gene transfer of mouse adiponectin plasmid DNA into gastrocnemius muscle resulted in elevated serum levels of globular and high-molecular weight adiponectin compared with control mice treated with empty plasmid. In comparison to HFHS-fed mice receiving empty plasmid, mice receiving adiponectin gene therapy displayed significantly decreased weight gain following 13 weeks of HFHS diet associated with reduced fat accumulation, and exhibited increased oxygen consumption and locomotor activity as measured by indirect calorimetry, suggesting increased energy expenditure in these mice. Consistent with improved whole-body metabolism, mice receiving adiponectin gene therapy also had lower blood glucose and insulin levels, improved glucose tolerance and reduced hepatic gluconeogenesis compared with control mice. Furthermore, immunoblot analysis of livers from mice receiving adiponectin gene therapy showed an increase in insulin-stimulated phosphorylation of insulin signaling proteins. Conclusion: Based on these data, we conclude that adiponectin gene therapy ameliorates the metabolic abnormalities caused by feeding mice a HFHS diet and may be a potential therapeutic strategy to improve obesity-mediated impairments in insulin sensitivity. PMID:23446660

Improving Adiponectin Levels in Individuals With Diabetes and Obesity: Insights From Look AHEAD.

PubMed

Belalcazar, L Maria; Lang, Wei; Haffner, Steven M; Schwenke, Dawn C; Kriska, Andrea; Balasubramanyam, Ashok; Hoogeveen, Ron C; Pi-Sunyer, F Xavier; Tracy, Russell P; Ballantyne, Christie M

2015-08-01

This study investigated whether fitness changes resulting from lifestyle interventions for weight loss may independently contribute to the improvement of low adiponectin levels in obese individuals with diabetes. Look AHEAD (Action for Health in Diabetes) randomized overweight/obese individuals with type 2 diabetes to intensive lifestyle intervention (ILI) for weight loss or to diabetes support and education (DSE). Total and high-molecular weight adiponectin (adiponectins), weight, and cardiorespiratory fitness (submaximal exercise stress test) were measured in 1,397 participants at baseline and at 1 year, when ILI was most intense. Regression analyses examined the associations of 1-year weight and fitness changes with change in adiponectins. ILI resulted in greater improvements in weight, fitness, and adiponectins at 1 year compared with DSE (P < 0.0001). Weight loss and improved fitness were each associated with changes in adiponectins in men and women (P < 0.001 for all), after adjusting for baseline adiponectins, demographics, clinical variables, and treatment arm. Weight loss contributed an additional 4-5% to the variance of change in adiponectins than did increased fitness in men; in women, the contributions of improved fitness (1% greater) and of weight loss were similar. When weight and fitness changes were both accounted for, weight loss in men and increased fitness in women retained their strong associations (P < 0.0001) with adiponectin change. Improvements in fitness and weight with ILI were favorably but distinctly associated with changes in adiponectin levels in overweight/obese men and women with diabetes. Future studies need to investigate whether sex-specific biological determinants contribute to the observed associations. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Adiponectin and Mortality in Smokers and Non-Smokers of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study.

PubMed

Delgado, Graciela E; Siekmeier, Rüdiger; März, Winfried; Kleber, Marcus E

2016-01-01

Cardiovascular diseases (CVD) are an important cause of morbidity and mortality worldwide. A decreased concentration of adiponectin has been reported in smokers. The aim of this study was to analyze the effect of cigarette smoking on the concentration of adiponectin and potassium in active smokers (AS) and life-time non-smokers (NS) of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study, and the use of these two markers for risk prediction. Smoking status was assessed by a questionnaire and measurement of plasma cotinine concentration. The serum concentration of adiponectin was measured by ELISA. Adiponectin was binned into tertiles separately for AS and NS and the Cox regression was used to assess the effect on mortality. There were 777 AS and 1178 NS among the LURIC patients. Within 10 years (median) of follow-up 221 AS and 302 NS died. In unadjusted analyses, AS had lower concentrations of adiponectin. However, after adjustment for age and gender there was no significant difference in adiponectin concentration between AS and NS. In the Cox regression model adjusted for age and gender, adiponectin was significantly associated with mortality in AS, but not in NS, with hazard ratio (95 % CI) of 1.60 (1.14-2.24) comparing the third with first tertile. In a model further adjusted for the risk factors, such as diabetes mellitus, hypertension, coronary artery disease, body mass index, LDL-cholesterol and HDL-cholesterol, adiponectin was significantly associated with mortality with hazard ratio of 1.83 (1.28-2.62) and 1.56 (1.15-2.11) for AS and NS, respectively. We conclude that increased adiponectin is a strong and independent predictor of mortality in both AS and NS. The determination of adiponectin concentration could be used to identify individuals at increased mortality risk.

Knockout maternal adiponectin increases fetal growth in mice: potential role for trophoblast IGFBP-1

PubMed Central

Qiao, Liping; Wattez, Jean-Sebastien; Lee, Samuel; Guo, Zhuyu; Schaack, Jerome; Hay, William W.; Moretto Zita, Matteo; Parast, Mana; Shao, Jianhua

2016-01-01

Aims/hypothesis The main objective of this study was to investigate whether maternal adiponectin regulates fetal growth through the endocrine system in the fetal compartment. Methods Adiponectin knockout (Adipoq−/−) mice and in vivo adenovirus-mediated reconstitution were used to study the regulatory effect of maternal adiponectin on fetal growth. Primary human trophoblast cells were treated with adiponectin and a specific peroxisome proliferator-activated receptor α (PPARα) agonist or antagonist to study the underlying mechanism through which adiponectin regulates fetal growth. Results The body weight of fetuses from Adipoq−/− dams was significantly greater than that of wild-type dams at both embryonic day (E)14.5 and E18.5. Adenoviral vector-mediated maternal adiponectin reconstitution attenuated the increased fetal body weight induced by maternal adiponectin deficiency. Significantly increased blood glucose, triacylglycerol and NEFA levels were observed in Adipoq−/− dams, suggesting that nutrient supply contributes to maternal adiponectin-regulated fetal growth. Although fetal blood IGF-1 concentrations were comparable in fetuses from Adipoq−/− and wild-type dams, remarkably low levels of IGF-binding protein 1 (IGFBP-1) were observed in the serum of fetuses from Adipoq−/− dams. IGFBP-1 was identified in the trophoblast cells of human and mouse placentas. Maternal fasting robustly increased IGFBP-1 levels in mouse placentas, while reducing fetal weight. Significantly low IGFBP-1 levels were found in placentas of Adipoq−/− dams. Adiponectin treatment increased IGFBP-1 levels in primary cultured human trophoblast cells, while the PPARα antagonist, MK886, abolished this stimulatory effect. Conclusions/interpretation These results indicate that, in addition to nutrient supply, maternal adiponectin inhibits fetal growth by increasing IGFBP-1 expression in trophoblast cells. PMID:27495989

Adiponectin inhibits leptin signaling via multiple mechanisms to exert protective effects against hepatic fibrosis

PubMed Central

HANDY, Jeffrey A.; FU, Ping P.; KUMAR, Pradeep; MELLS, Jamie E.; SHARMA, Shvetank; SAXENA, Neeraj K.; ANANIA, Frank A.

2011-01-01

SYNOPSIS Adiponectin is protective against hepatic fibrosis, while leptin promotes fibrosis. In hepatic stellate cells (HSCs), leptin signals via a Janus Kinase 2/Signal Transducers and Activators of Transcription 3 (Jak2/Stat3) pathway, producing effects that enhance extracellular matrix deposition. Suppressors of Cytokine Signaling-3 (SOCS-3) and Protein Tyrosine Phosphatase-1B (PTP1B) are both negative regulators of Jak/Stat signaling, and recent studies demonstrated a role for adiponectin in regulating SOCS-3 expression. In this study we investigated mechanisms whereby adiponectin dampens leptin signaling and prevents excess ECM production. We treated culture-activated rat HSCs with recombinant adiponectin, leptin, both or neither, and also treated adiponectin knockout (Ad−/−) and wild-type mice with leptin and/or carbon tetrachloride (CCl4), or saline. We analyzed Jak2 and Ob-Rb phosphorylation, and PTP1B expression and activity. We also explored potential mechanisms through which adiponectin regulates SOCS-3/Ob-Rb association. Adiponectin inhibited leptin-stimulated Jak2 activation and Ob-Rb phosphorylation in HSCs, while both were increased in Ad−/− mice. Adiponectin stimulated PTP1B expression and activity, in vitro, while PTP1B expression was lower in Ad−/−mice than in wild-type mice. Adiponectin also promoted SOCS-3/Ob-R association, and blocked leptin-stimulated formation of extracellular TIMP-1/MMP-1 complexes, in vitro. These data suggest two novel mechanisms whereby adiponectin inhibits hepatic fibrosis: by promoting binding of SOCS-3 to Ob-Rb, and stimulating PTP1B expression and activity, thus inhibiting Jak2-Stat3 signaling at multiple points. PMID:21846328

Adiponectin inhibits leptin signalling via multiple mechanisms to exert protective effects against hepatic fibrosis.

PubMed

Handy, Jeffrey A; Fu, Ping P; Kumar, Pradeep; Mells, Jamie E; Sharma, Shvetank; Saxena, Neeraj K; Anania, Frank A

2011-12-15

Adiponectin is protective against hepatic fibrosis, whereas leptin promotes fibrosis. In HSCs (hepatic stellate cells), leptin signals via a JAK2 (Janus kinase 2)/STAT3 (signal transducer and activator of transcription 3) pathway, producing effects that enhance ECM (extracellular matrix) deposition. SOCS-3 (suppressor of cytokine signalling-3) and PTP1B (protein tyrosine phosphatase 1B) are both negative regulators of JAK/STAT signalling, and recent studies have demonstrated a role for adiponectin in regulating SOCS-3 expression. In the present study we investigate mechanisms whereby adiponectin dampens leptin signalling and prevents excess ECM production. We treated culture-activated rat HSCs with recombinant adiponectin, leptin, both or neither, and also treated adiponectin knockout (Ad-/-) and wild-type mice with leptin and/or carbon tetrachloride (CCl4) or saline. We analyse JAK2 and Ob-Rb (long form of the leptin receptor) phosphorylation, and PTP1B expression and activity. We also explore potential mechanisms through which adiponectin regulates SOCS-3-Ob-Rb association. Adiponectin inhibits leptin-stimulated JAK2 activation and Ob-Rb phosphorylation in HSCs, whereas both were increased in Ad-/- mice. Adiponectin stimulates PTP1B expression and activity in vitro, whereas PTP1B expression was lower in Ad-/-mice than in wild-type mice. Adiponectin also promotes SOCS-3-Ob-R association and blocks leptin-stimulated formation of extracellular TIMP-1 (tissue inhibitor of metalloproteinases-1)-MMP-1 (matrix metalloproteinase-1) complexes in vitro. These results suggest two novel mechanisms whereby adiponectin inhibits hepatic fibrosis: (i) by promoting binding of SOCS-3 to Ob-Rb, and (ii) by stimulating PTP1B expression and activity, thus inhibiting JAK2/STAT3 signalling at multiple points.

Adiponectin has a pivotal role in the cardioprotective effect of CP-3(iv), a selective CD36 azapeptide ligand, after transient coronary artery occlusion in mice.

PubMed

Huynh, David N; Bessi, Valérie L; Ménard, Liliane; Piquereau, Jérôme; Proulx, Caroline; Febbraio, Maria; Lubell, William D; Carpentier, André C; Burelle, Yan; Ong, Huy; Marleau, Sylvie

2018-02-01

CD36 is a multiligand receptor involved in lipid metabolism. We investigated the mechanisms underlying the cardioprotective effect of CP-3(iv), an azapeptide belonging to a new class of selective CD36 ligands. The role of CP-3(iv) in mediating cardioprotection was investigated because CD36 signaling leads to activation of peroxisome proliferator-activated receptor-γ, a transcriptional regulator of adiponectin. CP-3(iv) pretreatment reduced infarct size by 54% and preserved hemodynamics in C57BL/6 mice subjected to 30 min coronary ligation and reperfusion but had no effect in CD36-deficient mice. The effects of CP-3(iv) were associated with an increase in circulating adiponectin levels, epididymal fat adiponectin gene expression, and adiponectin transcriptional regulators ( Pparg, Cebpb, Sirt1) after 6 h of reperfusion. Reduced myocardial oxidative stress and apoptosis were observed along with an increase in expression of myocardial adiponectin target proteins, including cyclooxygenase-2, phospho-AMPK, and phospho-Akt. Moreover, CP-3(iv) increased myocardial performance in isolated hearts, whereas blockade of adiponectin with an anti-adiponectin antibody abrogated it. CP-3(iv) exerts cardioprotection against myocardial ischemia and reperfusion (MI/R) injury and dysfunction, at least in part, by increasing circulating and myocardial adiponectin levels. Hence, both paracrine and endocrine effects of adiponectin may contribute to reduced reactive oxygen species generation and apoptosis after MI/R, in a CD36-dependent manner.-Huynh, D. N., Bessi, V. L., Ménard, L., Piquereau, J., Proulx, C., Febbraio, M., Lubell, W. D., Carpentier, A. C., Burelle, Y., Ong, H., Marleau, S. Adiponectin has a pivotal role in the cardioprotective effect of CP-3(iv), a selective CD36 azapeptide ligand, after transient coronary artery occlusion in mice.

Association between lifestyle factors and plasma adiponectin levels in Japanese men.

PubMed

Tsukinoki, Rumi; Morimoto, Kanehisa; Nakayama, Kunio

2005-11-02

Adiponectin is an adipocyte-specific protein that plays a role in obesity, insulin resistant, lipid metabolism, and anti-inflammation. Hypoadiponectinemia may be associated with a higher risk for type 2 diabetes and cardiovascular disease. Some studies suggest that adiponectin levels are modulated by lifestyle factors, but little is known about the associations between lifestyle factors and plasma adiponectin levels in Japanese people. We therefore investigated the associations between lifestyle factors and plasma adiponectin levels in general Japanese men. The subjects were 202 Japanese male workers who participated in an annual health check. They provided details about anthropometrical data, blood collection, their use of prescribed medication, and the clinical history of their families. They also completed a self-administered questionnaire about their lifestyles. Subjects with plasma adiponectin levels below 4.0 microg/ml had significantly lower levels of HDL cholesterol and higher levels of BMI, SBP, DBP, total cholesterol, FBG, and platelets than did subjects with higher adiponectin levels. In multiple logistic regression after multiple adjustment, a plasma adiponectin level below 4.0 microg/ml was significantly associated with smoking (odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.01-4.30), a daily diet rich in deep-yellow vegetables (OR = 0.25, 95% CI= 0.07-0.91), frequent eating out (OR = 2.45, 95% CI = 1.19-5.08), and physical exercise two or more times a week (OR = 0.21, 95% CI = 0.06-0.74). Our findings show that adiponectin levels in general Japanese men are independently related to smoking, dietary factors, and physical exercise. We think that lifestyle habits might independently modulate adiponectin levels and that adiponectin might be the useful biomarker helping people to avoid developing type 2 diabetes and cardiovascular disease by modifying their lifestyles.

Adiponectin/resistin interplay in serum and in adipose tissue of obese and normal-weight individuals.

PubMed

Jonas, Marta Izabela; Kurylowicz, Alina; Bartoszewicz, Zbigniew; Lisik, Wojciech; Jonas, Maurycy; Domienik-Karlowicz, Justyna; Puzianowska-Kuznicka, Monika

2017-01-01

The interplay between adiponectin and resistin, the two adipokines of opposite effects, may determine the metabolic profile of obese individuals and development of obesity-related complications. The current study was conducted to assess how adiponectin/resistin interplay in sera and adipose tissues may influence the metabolic profile of obese and normal-weight subjects. Concentrations of adiponectin and resistin were measured on protein level by immunoassay in visceral and subcutaneous adipose tissues from 50 obese (body mass index > 40 kg/m 2 ) and 28 normal-weight (body mass index 20-24.9 kg/m 2 ) individuals. Simultaneously expression of ADIPOQ and RETN (encoding adiponectin and resistin, respectively) was assessed on mRNA level by real-time PCR. ADIPOQ mRNA (P = 0.0001) and adiponectin protein (P = 0.0013) levels were lower, while RETN mRNA (P = 0.0338) and resistin (P < 0.0001)-higher in subcutaneous adipose tissues of obese subjects. ADIPOQ and RETN mRNA levels did not correlate with protein concentrations in the investigated adipose tissues. In obesity adiponectin serum concentrations correlated positively with ADIPOQ mRNA in subcutaneous adipose tissue (P = 0.005) and negatively with protein levels in visceral adipose tissue (P = 0.001). Obesity was associated with higher adiponectin-resistin index value in sera (P < 0.0001) and decreased in subcutaneous adipose tissue (P < 0.001), but only adiponectin-resistin index measured in sera was significantly higher in obese with the metabolic syndrome (P = 0.04). Obesity affects synthesis of adiponectin and resistin mainly in subcutaneous adipose tissue. The adiponectin-resistin index assessed in the adipose tissues has a different prognostic value compared to the adiponectin-resistin index in serum and does not reflect a metabolic risk in obese individuals.

Sex-dependent reductions in high molecular weight adiponectin during acute hyperinsulinemia are prevented with endurance training in older females.

PubMed

Consitt, Leslie A; Saxena, Gunjan; Schaefer, Megan

2018-05-01

The high molecular weight (HMW) adiponectin isoform is considered the active form of adiponectin and is linked to insulin sensitivity and the reduced risk of developing cardiovascular disease. The purpose of the first study was to determine the effects of age and sex on the plasma HMW adiponectin response to acute hyperinsulinemia, and secondly determine whether either endurance or resistance exercise training could affect this response. Twenty-six healthy males (19-84 years) and twenty-six healthy females (18-76 years) were recruited and matched for BMI to examine the effects of sex and age on the plasma adiponectin response to a 2-hour hyperinsulinemic-euglycemic clamp. To examine the effects of exercise training, a subgroup of young (<35 years) and aged (>55 years) individuals were randomized into a 12-week endurance or resistance training programme and had their adiponectin response to hyperinsulinemia measured before and after training. High molecular weight (HMW) and total adiponectin were measured by ELISA. In response to hyperinsulinemia, plasma HMW adiponectin decreased in females (-9%, P < .005), but not males. After 12 weeks of endurance training, the response of plasma HMW adiponectin to hyperinsulinemia increased in older females (36%, P < .05) only. Resistance training had no effect on the plasma adiponectin response to hyperinsulinemia. Despite no age or sex differences at baseline, skeletal muscle AdipoR1 increased in response to endurance training (~120%, P < .001) and resistance training (~38%, P < .05), regardless of age or sex. The inhibitory action of hyperinsulinemia on plasma HMW adiponectin occurs in females but not males, irrespective of age. Twelve weeks of endurance training protects older females against the hyperinsulinemic inhibition of plasma HMW adiponectin, which could promote healthy ageing. © 2018 John Wiley & Sons Ltd.

Time-dependent changes of plasma adiponectin concentration in relation to coronary microcirculatory function in patients with acute myocardial infarction treated by primary percutaneous coronary intervention.

PubMed

Trifunovic, Danijela; Stankovic, Sanja; Marinkovic, Jelena; Beleslin, Branko; Banovic, Marko; Djukanovic, Nina; Orlic, Dejan; Tesic, Milorad; Vujisic-Tesic, Bosiljka; Petrovic, Milan; Nedeljkovic, Ivana; Stepanovic, Jelena; Djordjevic-Dikic, Ana; Giga, Vojislav; Ostojic, Miodrag

2015-03-01

To analyze plasma adiponectin kinetics in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI) and its association with coronary flow reserve (CFR), an index of coronary microcirculatory function. A total of 96 consecutive patients with the first anterior STEMI treated by pPCI without heart failure were included. CFR was assessed on the 7th day after pPCI. Plasma adiponectin was measured on admission before pPCI, and on the 2nd and 7th day after pPCI. Adiponectin concentration was the highest on admission, declined to the lowest level on the 2nd day, and rose on the 7th day remaining below admission values. Impaired coronary microcirculatory function (CFR<2) was observed in 41% of the patients. Adiponectin concentrations significantly positively correlated with CFR, and the strongest correlation was with the 2nd day adiponectin (r=0.489, p<0.001). In multivariate models, adiponectin concentrations were independent predictors of impaired CFR [on admission: odds ratio (OR) 0.175, confidence interval (CI): 0.047-0.654, p=0.010; 2nd day: OR 0.146, 95% CI: 0.044-0.485, p=0.002; 7th day: OR 0.198, CI: 0.064-0.611, p=0.005]. The best power to predict impaired CFR was the 2nd day adiponectin. Delta values of adiponectin (differences between adiponectin concentrations) did not correlate with CFR. In patients with the first anterior STEMI treated by pPCI plasma adiponectin concentrations before and after pPCI are strongly associated with CFR. Our results support the hypothesis that low adiponectin, especially during the early post-pPCI period, carries the risk for impaired coronary microcirculatory function in STEMI patients. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Downregulation of adiponectin system in granulosa cells and low levels of HMW adiponectin in PCOS.

PubMed

Artimani, Tayebe; Saidijam, Massoud; Aflatoonian, Reza; Ashrafi, Mahnaz; Amiri, Iraj; Yavangi, Mahnaz; SoleimaniAsl, Sara; Shabab, Nooshin; Karimi, Jamshid; Mehdizadeh, Mehdi

2016-01-01

The purpose of the study was to investigate changes in adiponectin system expression in granulosa cells (GCs) and high molecular weight adiponectin levels in serum and follicular fluid (FF) of 40 women with polycystic ovary syndrome (PCOS) compared to those in 40 women with normal ovary function. Adiponectin (Adipo), adiponectin receptor 1 (AdipoR1), and adiponectin receptor 2 (AdipoR2) messenger RNA (mRNA) expression levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). High molecular weight (HMW) adiponectin protein concentration was evaluated by ELISA method. Data were analyzed using Student's t test and one-way ANOVA in SPSS 21 software. At oocyte retrieval, FF was aspirated and GCs were obtained from a pooled collection of FF per each patient. PCR results showed expression of adiponectin, AdipoR1, AdipoR2, follicle-stimulating hormone receptor (FSHR), and luteinizing hormone receptor (LHR) in GCs. After controlling body mass index (BMI) values, qRT-PCR demonstrated a decreased expression of adiponectin system in GCs of PCOS patients compared to those in controls (p = 0.001). There was a strong positive correlation among AdipoR1 and AdipoR2 expression and also among FSH and LH receptor expression. (Both r = 0.8, p = 0.001). There were low levels of high molecular weight adiponectin in the serum of PCOS patients with controlled ovarian hyperstimulation (30.19 ± 4.3 ng/ml) compared to the controls (48.47 ± 5.9 ng/ml) and in the FF of PCOS patients with controlled ovarian hyperstimulation (7.86 ± 1.44 ng/ml) compared to the controls (14.22 ± 2.01 ng/ml; p = 0.02). Lower expression of adiponectin and its receptors in GCs might be an important manifestation in gonadotropin-stimulated PCOS patients which could influence the physiologic adiponectin roles such as interaction with insulin and LH in induction of GC gene expression.

Effects of acute hyperinsulinaemia on total and high-molecular-weight adiponectin concentration in metabolically healthy but obese postmenopausal women: a Montreal-Ottawa New Emerging Team (MONET) study.

PubMed

Elisha, B; Karelis, A D; Imbeault, P; Rabasa-Lhoret, R

2010-09-01

The aim of this study was to determine the differences and changes in total and high-molecular-weight (HMW) adiponectin levels among metabolically healthy but obese (MHO) postmenopausal women in response to acute hyperinsulinaemia. In this cross-sectional study, 55 non-diabetic overweight and obese postmenopausal women underwent a hyperinsulinaemic-euglycaemic clamp test to evaluate insulin sensitivity. Subjects within the upper tertile of insulin sensitivity were described as 'MHO' (n=18), whereas those within the lowest tertile were considered 'at risk' (n=18). Plasma total and HMW adiponectin levels were measured by ELISA at 0 (baseline), 90, 160 and 180 min during the clamp. At baseline and at all time points during the clamp, MHO individuals had significantly higher total and HMW adiponectin levels than at-risk subjects (AUC: total adiponectin=2506 ± 1010 vs 1616 ± 830; HMW adiponectin=909 ± 307 vs 604 ± 349; P<0.05). In addition, a significant reduction in total adiponectin was observed at 160 min and 180 min in at-risk and MHO subjects, respectively, while HMW adiponectin significantly decreased at 160 min in at-risk subjects, and at 90 min as well as 160 min in MHO women. MHO postmenopausal women had higher levels of plasma total and HMW adiponectin than at-risk subjects at baseline and during the clamp. Furthermore, significant decreases in total and HMW adiponectin were observed at certain time points in both the MHO and at-risk subjects. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

[Adiponectin levels in breast milk of overweight/obese and normal weight mothers in the metropolitan area of Monterrey, México].

PubMed

Galindo Gómez, Abelardo; Flores Scheufler, Pamela; Quevedo Escobar, Yamile; González Magaña, Regina; Rodríguez De Ita, Julieta

Given the current epidemic of childhood obesity, it has become increasingly important to understand the risks and protective factors associated with this disease. Breastfeeding has been identified as a protective factor; however, the mechanism responsible has not been elucidated. One of the current theories analyzes the role of hormones in breast milk, with special emphasis on adiponectin. This study aims to compare adiponectin levels in breast milk of mothers with normal weight with those in breast milk of overweight/obese mothers as well as to correlate these levels with the infant's weight gain. Forty samples of breast milk were analyzed for adiponectin levels using ELISA, 20 from mothers with normal weight and 20 from overweight/obese mothers. Adiponectin levels were lower in breast milk obtained from overweight/obese mothers than in breast milk from mothers with normal weight (p <0.05). When comparing infant weight gain, those fed with breast milk containing higher concentrations of adiponectin had a lower weight gain than those fed with breast milk containing low levels of the hormone (p <0.05). There is a strong negative correlation between mothers' BMI and adiponectin levels in breast milk. Mothers with a higher BMI had lower adiponectin levels in their breast milk. There is also a negative relationship between adiponectin levels in breast milk and weight gain of breastfed infants. Infants breast fed with adiponectin-rich breast milk had a lower weight gain. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Role of Adiponectin in Coronary Heart Disease Risk

PubMed Central

Lawlor, Debbie A.; de Oliveira, Cesar; White, Jon; Horta, Bernardo Lessa; Barros, Aluísio J.D.

2016-01-01

Rationale: Hypoadiponectinemia correlates with several coronary heart disease (CHD) risk factors. However, it is unknown whether adiponectin is causally implicated in CHD pathogenesis. Objective: We aimed to investigate the causal effect of adiponectin on CHD risk. Methods and Results: We undertook a Mendelian randomization study using data from genome-wide association studies consortia. We used the ADIPOGen consortium to identify genetic variants that could be used as instrumental variables for the effect of adiponectin. Data on the association of these genetic variants with CHD risk were obtained from CARDIoGRAM (22 233 CHD cases and 64 762 controls of European ancestry) and from CARDIoGRAMplusC4D Metabochip (63 746 cases and 130 681 controls; ≈ 91% of European ancestry) consortia. Data on the association of genetic variants with adiponectin levels and with CHD were combined to estimate the influence of blood adiponectin on CHD risk. In the conservative approach (restricted to using variants within the adiponectin gene as instrumental variables), each 1 U increase in log blood adiponectin concentration was associated with an odds ratio for CHD of 0.83 (95% confidence interval, 0.68–1.01) in CARDIoGRAM and 0.97 (95% confidence interval, 0.84–1.12) in CARDIoGRAMplusC4D Metabochip. Findings from the liberal approach (including variants in any locus across the genome) indicated a protective effect of adiponectin that was attenuated to the null after adjustment for known CHD predictors. Conclusions: Overall, our findings do not support a causal role of adiponectin levels in CHD pathogenesis. PMID:27252388

Relative contribution of obesity and menopause to the association between serum adiponectin and incident metabolic syndrome.

PubMed

Ahn, Song Vogue; Jung, Dong-Hyuk; Yadav, Dhananjay; Kim, Jang-Young; Koh, Sang-Baek

2018-02-01

Metabolic syndrome is closely linked to obesity. Menopause may play a critical role in understanding the pathophysiology of metabolic syndrome in women. We investigated the relative contribution of obesity and menopause to the association between serum adiponectin levels and the development of metabolic syndrome. A prospective cohort study was conducted in which a total of 1,219 women without metabolic syndrome were examined at baseline (2005-2008) and followed up (2008-2011). Women were divided according to tertiles of serum adiponectin levels and menopause status, and then stratified into four groups: the nonobese with high adiponectin; the nonobese with low adiponectin; the obese with high adiponectin; and the obese with low adiponectin. During an average 2.5-year follow-up, 44 premenopausal women (9.8%) and 161 postmenopausal women (20.9%) developed metabolic syndrome. The obese group with low serum adiponectin demonstrated an increased risk for developing metabolic syndrome in both premenopausal (odds ratio [OR] 5.92, 95% confidence interval [CI] 2.24-15.66) and postmenopausal women (OR 4.22, 95% CI 2.41-7.36). However, the inverse association between serum adiponectin levels and incidence of metabolic syndrome was observed in premenopausal women with obesity (OR 0.16, 95% CI 0.03-0.81), but not in postmenopausal women with obesity (OR 0.55, 95% CI 0.27-1.14). High serum adiponectin levels showed no inverse association with metabolic syndrome in postmenopausal women with obesity. These findings may suggest a need for closer management of metabolic risk in postmenopausal women.

Influence of nutritional status and VO2max on adiponectin levels in men older than 35 years. [corrected].

PubMed

Martinez, Eduardo Camillo; Fortes, Macos de Sá Rego; Anjos, Luiz Antônio dos

2011-06-01

Adiponectin is considered an important factor in the pathogenesis of cardiovascular and metabolic diseases, due to its anti- atherogenic and anti-inflammatory properties. Few studies, however, have suggested the existence of a direct association between adiponectin levels and cardiorespiratory fitness and physical activity levels. To verify the influence of the nutritional status and cardiorespiratory fitness on plasma adiponectin levels in adult men. A total of 250 subjects, all in active duty in the Brazilian Army (BA), with a mean age of 42,6 ± 4,8 years volunteered to participate in the study. Plasma levels of adiponectin were measured, as well as body mass, height, waist circumference (WC), fat percentage by hydrostatic weighing and VO(2max) by ergospirometry. A questionnaire was used to obtain the characteristics of the physical training performed by the individuals. The sample showed that 121 (48%) individuals were overweight and 36 (14%) were obese. Moreover, 66 individuals (27%) had a body fat percentage > 25% and 26,7% had a WC > 94 cm. Overweight and obese individuals had significantly lower adiponectin levels than those with an adequate nutritional status. Individuals at the highest tertile of VO(2max) had higher adiponectin levels than the others. The adiponectin levels were positively correlated with the total weekly physical training time and VO(2max) and inversely correlated with body mass, BMI and WC. The correlation between adiponectin levels and VO(2max) did not remain significant after being adjusted for BMI and WC. Individuals with better cardiorespiratory fitness and normal nutritional status seem to present healthier levels of adiponectin.

The relationship between insulin sensitivity and serum adiponectin levels in three population groups.

PubMed

Ferris, W F; Naran, N H; Crowther, N J; Rheeder, P; van der Merwe, L; Chetty, N

2005-11-01

Reduced plasma adiponectin levels are associated with insulin resistance. Black South Africans, like African Americans, are more insulin-resistant than BMI-matched white subjects, as are Asian Indians. We investigated whether this interethnic variation in insulin resistance is due to differences in plasma adiponectin levels. Blood and anthropometric measurements were taken from black, white and Asian-Indian subjects. Serum adiponectin, lipids, glucose and insulin were measured; insulin sensitivity was calculated using HOMA. Black (HOMA = 2.62 +/- 0.99) and Asian-Indian subjects (HOMA = 3.41 +/- 2.85) were more insulin-resistant than BMI-matched white (HOMA = 1.76 +/- 0.63) subjects (p = 0.0001). Furthermore, the white subjects had higher adiponectin levels (8.11 +/- 4.39 microg/ml) compared to black (5.71 +/- 2.50 microg/ml) and Asian Indian (5.86 +/- 2.50 microg/ml) subjects (p = 0.003). When all ethnic groups were combined, multiple regression analysis demonstrated that serum adiponectin levels corrected for BMI and ethnicity did not correlate with HOMA, but did explain 10.0 % of the variance in HDL-cholesterol levels. Within each ethnic group, adiponectin only correlated inversely with HOMA in white subjects. Adiponectin may play a role in determining serum HDL-cholesterol levels, but ethnic variation in insulin sensitivity is not dependent on serum levels of this adipokine. The relationship between adiponectin and insulin resistance varies across ethnic groups.

Adiponectin is partially associated with exosomes in mouse serum.

PubMed

Phoonsawat, Worrawalan; Aoki-Yoshida, Ayako; Tsuruta, Takeshi; Sonoyama, Kei

2014-06-06

Exosomes are membrane vesicles 30-120 nm in diameter that are released by many cell types and carry a cargo of proteins, lipids, mRNA, and microRNA. Cultured adipocytes reportedly release exosomes that may play a role in cell-to-cell communication during the development of metabolic diseases. However, the characteristics and function of exosomes released from adipocytes in vivo remain to be elucidated. Clearly, adipocyte-derived exosomes could exist in the circulation and may be associated with adipocyte-specific proteins such as adipocytokines. We isolated exosomes from serum of mice by differential centrifugation and analyzed adiponectin, leptin, and resistin in the exosome fraction. Western blotting detected adiponectin but no leptin and only trace amounts of resistin in the exosome fraction. The adiponectin signal in the exosome fraction was decreased by proteinase K treatment and completely quenched by a combination of proteinase K and Triton X-100. Quantitative ELISA showed that the exosome fraction contains considerable amounts of adiponectin, but not leptin or resistin. The concentration of adiponectin in the serum and the ratio of adiponectin to total protein in the exosome fraction were lower in obese mice than in lean mice. These results suggest that a portion of adiponectin exists as a transmembrane protein in the exosomes in mouse serum. We propose adiponectin as a marker of exosomes released from adipocytes in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.

Combined Adiponectin Deficiency and Resistance in Obese Patients: Can It Solve Part of the Puzzle in Nonalcoholic Steatohepatitis.

PubMed

Salman, Ahmed; Hegazy, Mona; AbdElfadl, Soheir

2015-06-15

Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease, nonalcoholic steatohepatitis (NASH) and fibrosis in obese patients identifies the risk group with increased incidence of liver-related deaths. To clarify the role of serum adiponectin and its receptor liver gene expression in the progression of liver damage in NAFLD. Fifty four (54) obese patients with NAFLD preliminary diagnosed by liver ultra-sound were recruited. Full medical history, anthropometric measurement, biochemical studies, serum adiponectin level, liver biopsy for histological examination and NAS score to identify NASH patients, and assessment of adiponectin receptor gene expression by RT-PCR, were conducted for each patients. Fifteen ages matched average weight healthy adult had been chosen as a control for serum adiponectin level. According to NAS score, patients were divided into non- NASH (8 patients), and NASH (46 patients). Serum adiponectin level was significantly lower in NAFLD patients compared to normal participants (p < 0.004). Serum adiponectin level was lower in NASH patients (4.437 ± 2.569 ng/dl in NASH vs. 5.138 ± 2.841 ng/dl in non-NASH). Adiponectin receptor liver gene expression was lower in NASH patients (0.8459 ± 0.4671 vs. 1.0688 ± 0.3965 in non-NASH). Both adiponectin deficiency and resistance had a role in progression of simple liver steatosis to severe injury in obese patients.

Intercellular adhesion molecule, plasma adiponectin and albuminuria in type 2 diabetic patients.

PubMed

Lenghel, Alina Ramona; Kacso, Ina Maria; Bondor, Cosmina Ioana; Rusu, Crina; Rahaian, Rodica; Gherman Caprioara, Mirela

2012-01-01

Our study addressed the influence of early inflammatory stages of diabetic kidney disease: leukocyte adhesion and monocyte activation (as assessed by intercellular leukocyte adhesion molecule-ICAM-1 and monocyte chemoatractant protein-MCP-1) on the degree of albuminuria. Plasma levels of adiponectin, a possible anti-inflammatory counteracting mechanism, were also studied in correlation to the above-mentioned cytokines. 79 consecutive type 2 diabetic outpatients and 46 controls were included. Routine laboratory analysis, urinary albumin to creatinine ratio (uACR), plasma adiponectin, plasma ICAM-1 and urinary MPC-1 were assessed. In multiple regression ICAM-1 (p=0.004) and adiponectin (p=0.04) were the main determinants of uACR. Plasma adiponectin positively correlated to ICAM-1 (p=0.03, r=0.24). In albuminuric patients (uACR ≥30 mg/g) plasma adiponectin was significantly higher compared to normoalbuminuric ones (uACR <30 mg/g). In albuminuric patients the main determinants of uACR were plasma ICAM-1 and adiponectin. In multiple regression ICAM-1 is the only one that retains statistical significance (p=0.02). Urinary MCP-1 did not correlate to uACR. In our type 2 diabetic patients, plasma levels of ICAM-1 and adiponectin are predictive for albuminuria. Urinary MCP-1 does not correlated to uACR. Plasma adiponectin positively correlates to adhesion molecule ICAM-1 in our cohort. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The circulating concentration and ratio of total and high molecular weight adiponectin in post-menopausal women with and without osteoporosis and its association with body mass index and biochemical markers of bone metabolism.

PubMed

Sodi, R; Hazell, M J; Durham, B H; Rees, C; Ranganath, L R; Fraser, W D

2009-09-01

There is increasing evidence suggesting that adiponectin plays a role in the regulation of bone metabolism. This was a cross-sectional study of 34 post-menopausal women with and 37 without osteoporosis. All subjects had body mass index (BMI), bone mineral density (BMD), total-, high molecular weight (HMW)-adiponectin and their ratio, osteoprotegerin (OPG), a marker of bone resorption (betaCTX) and formation (P1NP) measured. We observed a positive correlation between BMI and BMD (r=0.44, p<0.001). When normalised for BMI, total-, HMW-adiponectin concentrations and HMW/total-adiponectin ratio were significantly lower in obese compared to lean subjects but there was no difference between those with or without osteoporosis. There were significant negative correlations between HMW/total-adiponectin ratio and BMI (r=-0.27, p=0.030) and with OPG (r=-0.44, p<0.001). Our data suggests that there is no significant difference in the circulating concentration of fasting early morning total- or HMW-adiponectin in post-menopausal women with or without osteoporosis. The correlation between HMW/total-adiponectin ratio and OPG may indicate that adiponectin could influence bone metabolism by altering osteoblast production of OPG thereby affecting osteoclasts mediated bone resorption.

Association of Serum Vaspin and Adiponectin Levels with Renal Function in Patients with or without Type 2 Diabetes Mellitus

PubMed Central

Yan, Meiyu; Su, Bin; Peng, Wenhui; Li, Liang; Li, Hailing; Zhuang, Jianhui; Lu, Yuyan; Jian, Weixia; Wei, Yidong; Li, Weiming; Qu, Shen; Xu, Yawei

2014-01-01

Vaspin and adiponectin are two adipocytokines with antidiabetic effects. Some studies reported that levels of adiponectin and vaspin were correlated with decreased glomerular filtration rate (FGR) and increased albuminuria. We therefore evaluated the vaspin and adiponectin levels in renal insufficiency (RI) patients with or without T2DM. Serum vaspin, adiponectin levels were measured in 416 subjects with or without T2DM. Analysis was made between groups divided by these subjects presence or absence of RI. We found that serum adiponectin level was significantly higher in nondiabetic patients with RI than in nondiabetic subjects without RI; however, there were no statistical differences between the diabetic patients with RI and without RI. In all the subjects, the serum adiponectin level was also higher in 50 individuals with RI than that in 366 subjects without RI. The serum vaspin levels showed no significant differences between the diabetic patients or nondiabetics subjects with RI and without RI. Contrary to adiponectin, the serum vaspin level was lower in 169 patients with T2DM than in 247 individuals without T2DM. Our data suggested that both of T2DM and renal insufficiency were correlated with the serum level of adiponectin. However, the serum vaspin levels showed no significant difference between the individuals with renal insufficiency and without renal insufficiency. PMID:25133192

A disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerization

PubMed Central

Liu, Meilian; Zhou, Lijun; Xu, Aimin; Lam, Karen S. L.; Wetzel, Michael D.; Xiang, Ruihua; Zhang, Jingjing; Xin, Xiaoban; Dong, Lily Q.; Liu, Feng

2008-01-01

Impairments in adiponectin multimerization lead to defects in adiponectin secretion and function and are associated with diabetes, yet the underlying mechanisms remain largely unknown. We have identified an adiponectin-interacting protein, previously named GST-kappa, by yeast 2-hybrid screening. The adiponectin-interacting protein contains 2 thioredoxin domains and has very little sequence similarity to other GST isoforms. However, this protein shares high sequence and secondary structure homology to bacterial disulfide-bond A oxidoreductase (DsbA) and is thus renamed DsbA-like protein (DsbA-L). DsbA-L is highly expressed in adipose tissue, and its expression level is negatively correlated with obesity in mice and humans. DsbA-L expression in 3T3-L1 adipocytes is stimulated by the insulin sensitizer rosiglitazone and inhibited by the inflammatory cytokine TNFα. Overexpression of DsbA-L promoted adiponectin multimerization while suppressing DsbA-L expression by RNAi markedly and selectively reduced adiponectin levels and secretion in 3T3-L1 adipocytes. Our results identify DsbA-L as a key regulator for adiponectin biosynthesis and uncover a potential new target for developing therapeutic drugs for the treatment of insulin resistance and its associated metabolic disorders. PMID:19011089

Adiponectin inhibits leptin-induced oncogenic signalling in oesophageal cancer cells by activation of PTP1B.

PubMed

Beales, Ian L P; Garcia-Morales, Carla; Ogunwobi, Olorunseun O; Mutungi, Gabriel

2014-01-25

Obesity is characterised by hyperleptinaemia and hypoadiponectinaemia and these metabolic abnormalities may contribute to the progression of several obesity-associated cancers including oesophageal adenocarcinoma (OAC). We have examined the effects of leptin and adiponectin on OE33 OAC cells. Leptin stimulated proliferation, invasion and migration and inhibited apoptosis in a STAT3-dependant manner. Leptin-stimulated MMP-2 secretion in a partly STAT3-dependent manner and MMP-9 secretion via a STAT3-independent pathway. Adiponectin inhibited leptin-induced proliferation, migration, invasion, MMP secretion and reduced the anti-apoptotic effects: these effects of adiponectin were ameliorated by both a non-specific tyrosine phosphatase inhibitor and a specific PTP1B inhibitor. Adiponectin reduced leptin-stimulated JAK2 activation and STAT3 transcriptional activity in a PTP1B-sensitive manner and adiponectin increased both PTP1B protein and activity. We conclude that adiponectin restrains leptin-induced signalling and pro-carcinogenic behaviour by inhibiting the early events in leptin-induced signal transduction by activating PTP1B. Relative adiponectin deficiency in obesity may contribute to the promotion of OAC. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

DYSREGULATION OF MATERNAL SERUM ADIPONECTIN IN PRETERM LABOR

PubMed Central

Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Erez, Offer; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Pacora, Percy; Yeo, Lami; Gotsch, Francesca; Dong, Zhong; Nhan-Chang, Chia-Ling; Jodicke, Cristiano; Yoon, Bo Hyun; Hassan, Sonia S.; Kusanovic, Juan Pedro

2013-01-01

Objective Intra-amniotic and systemic infection/inflammation have been causally linked to preterm parturition and fetal injury. An emerging theme is that adipose tissue can orchestrate a metabolic response to insults, but also an inflammatory response via the production of adipocytokines, and that these two phenomenon are interrelated. Adiponectin, an insulin-sensitizing, anti-inflammatory adipocytokine, circulates in multimeric complexes including low-molecular-weight (LMW) trimers, medium-molecular-weight (MMW) hexamers and high-molecular-weight (HMW) isoforms. Each of these complexes can exert differential biological effects. The aim of this study was to determine whether spontaneous preterm labor (PTL) with intact membranes and intra-amniotic infection/inflammation (IAI) is associated with changes in maternal serum circulating adiponectin multimers. Study design This cross-sectional study included patients in the following groups: 1) normal pregnant women (n=158); 2) patients with an episode of preterm labor and intact membranes without IAI who delivered at term (n=41); 3) preterm labor without IAI who delivered preterm (n=27); and 4) preterm labor with IAI who delivered preterm (n=36). Serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results 1) Preterm labor leading to preterm delivery or an episode of preterm labor which does not lead to preterm delivery, was associated with a lower median maternal serum concentration of total and HMW adiponectin, a lower median HMW/total adiponectin ratio, and a higher median LMW/total adiponectin ratio than normal pregnancy; 2) among patients with preterm labor, those with IAI had the lowest median concentration of total and HMW adiponectin, as well as the lowest median HMW/total adiponectin ratio; 3) The changes in maternal adiponectin and adiponectin multimers remained significant after adjusting for confounding factors such as maternal age, BMI, gestational age at sampling, and parity. Conclusion 1) Preterm labor is characterized by a change in the profile of adiponectin multimers concentrations and their relative isoforms. These changes were observed in patients with an episode of preterm labor not leading to preterm delivery, in patients with intra-amniotic inflammation, or in those without evidence of intra-amniotic inflammation; 2) The changes in adiponectin multimer concentrations reported in preterm labor are different from those previously reported in spontaneous labor at term, suggesting that there is a fundamental difference between preterm labor and labor at term; 3) The findings reported herein, provide the first evidence for the participation of adiponectin multimer in preterm parturition. We propose that adiponectins and adipokines in general provide a mechanism to organize the metabolic demands generated by the process of preterm parturition regardless of the nature of the insult (intra-amniotic inflammation or not). PMID:19579094

Effects of training and detraining on adiponectin plasma concentration and muscle sensitivity in lean and overweight men.

PubMed

Gastebois, Caroline; Villars, Clément; Drai, Jocelyne; Canet-Soulas, Emmanuelle; Blanc, Stéphane; Bergouignan, Audrey; Lefai, Etienne; Simon, Chantal

2016-12-01

To delineate the direct effect of physical activity on adiponectin metabolism, we investigated the impact of contrasted physical activity changes, independent of body mass changes, on adiponectin plasma concentration and muscle sensitivity in lean and overweight adult males. Eleven physically active lean men (70.6 ± 2.1 kg) were subjected to 1-month detraining; 9 sedentary lean men (73.1 ± 3.3 kg); and 11 sedentary overweight men (97.5 ± 3.0 kg) participated in a 2-month aerobic-exercise training program. Diet was controlled to maintain stable energy balance. Body composition, VO 2peak , circulating adiponectin, adipose and muscle tissue adiponectin, muscle adiponectin receptors, and APPL1 mRNAs were measured before and after the interventions. At baseline, plasma high-molecular-weight adiponectin concentration was lower in both active lean (5.44 ± 0.58 µg/mL) and sedentary overweight (5.30 ± 1.06 µg/mL) than in sedentary lean participants (7.44 ± 1.06 µg/mL; both p < 0.05). Training reduced total and high-molecular-weight adiponectin concentrations by, respectively, -32 and -42 % in sedentary lean, and -26 and -35 % in sedentary overweight, while detraining increased them by +25 and +27 % in active lean participants. Total and high-molecular-weight adiponectin changes were inversely correlated with VO 2peak changes (respectively, R 2  = 0.45, R 2  = 0.59; both p < 0.001) and positively with changes in fasting plasma insulin (both p < 0.05). Muscle and adipose tissue adiponectin mRNA did not differ between groups and with interventions. Muscle AdipoR2 and APPL1 mRNAs were lower in sedentary groups compared with the active group; and were positively associated with VO 2peak and inversely with fasting plasma insulin concentration. Plasma adiponectin concentration is inversely correlated with aerobic capacity. Future investigations will need to confirm the contribution of changes in muscle adiponectin sensitivity.

Serum vascular endothelial growth factor and adiponectin levels in patients with benign and malignant gynecological diseases.

PubMed

Lasalandra, Carla; Coviello, Maria; Falco, Gaetano; Divella, Rosa; Trojano, Giuseppe; Laterza, Anna Maria; Quero, Carmela; Pepe, Vito; Zito, Francesco Alfredo; Quaranta, Michele

2010-05-01

One of the most specific and critical regulators of angiogenesis is vascular endothelial growth factor (VEGF), which regulates endothelial proliferation, permeability, and survival. Vascular endothelial growth factor is an angiogenic mediator in tumors and has been implicated in the pathogenesis and progression of cancer. Adipose tissue is a major endocrine and it secretes hormones termed adipokines. These factors are derived from adipocytes and include proteins and metabolites such as adiponectin. Recently, adiponectin was also shown to modulate angiogenesis. This study was designed to determine the serum VEGF and adiponectin levels in patients with benign and malignant gynecological diseases and if there was a correlation between serum VEGF and adiponectin. Serum samples, collected fasting before surgery or intervention, were available for total of 114 female patients recorded between October 2006 and December 2008. Diagnosis of benign and malignant gynaecological diseases was established by biopsy. Serum levels VEGF and adiponectin were using commercially available enzyme linked immunosorbent assay (R&D Systems Inc, Minneapolis, MN), respectively. Statistical analysis was performed by using the SPSS 9.0 software package (SPSS, Inc, Chicago, IL). The correlation between serum VEGF and serum Adiponectin was calculated using the Pearson correlation coefficient. P values of < 0.05 were considered statistically significant. Our results were analyzed on the basis of 2 different parameters: age and benign and malignant gynecological diseases of the patient. Only for serum VEGF levels was a significant difference observed (P = 0.004) between patients with benign and malignant gynecological diseases. A significantly inverse correlation between serum VEGF and adiponectin levels among patients with benign and malignant gynecological diseases was found. Adiponectin level is not correlated with body mass index. This is one of the first report on adiponectin in benign and malignant gynecological diseases. Future studies are needed to address the clinical potential role of adiponectin in cancer.

The significance of adiponectin as a biomarker in metabolic syndrome and/or coronary artery disease.

PubMed

Stojanović, Sanja; Ilić, Marina Deijanin; Ilić, Stevan; Petrović, Dejan; Djukić, Svetlana

2015-09-01

BACKGROUND/AIM. Adiponectin exerts profound protective actions during insulin resistence or prediabetes progression towards more severe clinical entities such as metabolic syndrome and/or cardiovascular disease. Since hypoadiponectinaemia contributes to the pathophysiology of the metabolic syndrome and coronary artery disease the level of circulating adiponectin may be an early marker of cardiovascular events. The aim of this study was to determine the relationships between serum adiponectin levels and parameters of both insulin sensitivity and obesity in patients with the metabolic syndrome and/or coronary artery disease, as well as to assess predictive value of adiponectin serum levels as a biomarker of these entitetis. The study included 100 patients with metabolic syndrome and/or coronary artery disease with different degree of insulin resistance and healthy, normoglycemic individuals. The control group comprising healthy, normoglycemic individuals was used for comparison. Serum level of adiponectin, fasting glucose, fasting insulinemia Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index and anthropometric parameters were determined in all the subjects. Adiponectin was measured by using the ultrasensitive ELISA method. Insulinemia was measured by the radioimmunoassay (RIA) method. The presence of glycemic disorders was assessed on the basis of oral glucose tolerance test (OGTT). Results. Adiponectin level was inversely correlated with age (ρ = -0.015), parameters of both obesity (R = 0.437;p < 0.001) and insulin resistance (R = 0.374; p < 0.01). Decreasing in the level of adiponecrin was strongly implicated in the development of insulin resistance. Most importantly, a statistically significant rapid decrease ih adiponectin was in the prediabetic stages (p < 0.01). The predictor value of adiponectin was 1,356.32 ± 402.65 pg/mL. The obtained resultats suggest that adiponectin may be a useful marker in identification of individuals with risk of developing metabolic syndrome and coronary artery disease, as well as a predictor of prediabetes.

Cardio-adipose tissue cross-talk: relationship between adiponectin, plasma pro brain natriuretic peptide and incident heart failure.

PubMed

Lindberg, Søren; Jensen, Jan Skov; Bjerre, Mette; Pedersen, Sune H; Frystyk, Jan; Flyvbjerg, Allan; Mogelvang, Rasmus

2014-06-01

There is increasing evidence of cross-talk between the heart, body metabolism, and adipose tissue, but the precise mechanisms are poorly understood. Natriuretic peptides (NPs) have recently emerged as the prime candidate for a mediator. In patients with heart failure (HF), infusion of NPs increases adiponectin secretion, indicating that NPs may improve adipose tissue function and in this way function as a cardio-protective agent in HF. Accordingly we investigated the interplay between plasma adiponectin, plasma proBNP, and development of HF. We prospectively followed 5574 randomly selected men and women from the community without ischaemic heart disease or HF. Plasma adiponectin and proBNP were measured at study entry. Median follow-up time was 8.5 years (interquartile range 8.0-9.1 years). During follow-up 271 participants developed symptomatic HF. Plasma adiponectin and proBNP were strongly associated (P < 0.001). Participants with increasing adiponectin had increased risk of incident HF (P < 0.001). After adjustment for confounding risk factors (including age, gender, smoking status, body mass ratio, waist-hip ratio, glucose, glycated haemoglobin, systolic and diastolic blood pressure, lipid profile, high sensitivity C-reactive protein, estimated glomerular filtration rate, and physical activity) by Cox regression analysis, adiponectin remained an independent predictor of HF: the hazard ratio (HR) per 1 standard deviation (SD) increase in adiponectin was 1.20 [95% confidence interval (CI) 1.06-1.30; P = 0.003]. However, the association vanished when plasma proBNP was included in the analysis, HR 1.08 (95% CI 0.95-1.23; P = 0.26). In conclusion, plasma adiponectin and proBNP are strongly associated. Increasing plasma adiponectin is associated with increased risk of HF. However, concomitantly elevated proBNP levels appear to explain the positive association between adiponectin and risk of HF. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance.

PubMed

Chang, Ming-Ling; Kuo, Chia-Jung; Pao, Li-Heng; Hsu, Chen-Ming; Chiu, Cheng-Tang

2017-10-03

The evolution of the relationship between adiponectin and insulin sensitivity in hepatitis C virus (HCV) patients during viral clearance is unclear and warrants investigation. A prospective study including 747 consecutive chronic hepatitis C (CHC) patients, of whom 546 had completed a course of anti-HCV therapy and underwent pre-, peri- and post-therapy surveys for anthropomorphic, viral, metabolic and hepatic profiles and adiponectin levels, was conducted in a tertiary care center. Multivariate analyses indicated associations of sex, triglyceride levels and hepatic steatosis with adiponectin levels and of triglyceride levels and interferon λ3 (IFNL3) genotype with homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels before anti-HCV therapy. In patients with a sustained virological response (SVR; n = 455), at 24 weeks post-therapy, sex, BMI, aspartate aminotransferase to platelet ratio index (APRI), HOMA-IR and steatosis were associated with adiponectin levels, and IFNL3 genotype was associated with HOMA-IR levels. GEE analysis demonstrated that SVR affected longitudinal trends in adiponectin levels. Compared with pre-therapy levels, adiponectin and APRI levels decreased 24 weeks post-therapy in SVR patients, regardless of baseline insulin resistance (IR). However, HOMA-IR levels decreased in SVR patients with baseline IR but increased in those without baseline IR. Compared with controls, immunohistochemical studies showed that pre-therapy CHC patients had higher hepatic adiponectin expression associated with hepatic fibrosis. During HCV infection, adiponectin may affect insulin sensitivity through triglycerides. After viral clearance, adiponectin levels were directly associated with insulin sensitivity and decreased upon improved hepatic fibrosis; with a link to the IFNL3 genotype, insulin sensitivity improved only in patients with baseline IR.

L-Cysteine supplementation increases adiponectin synthesis and secretion, and GLUT4 and glucose utilization by upregulating disulfide bond A-like protein expression mediated by MCP-1 inhibition in 3T3-L1 adipocytes exposed to high glucose.

PubMed

Achari, Arunkumar Elumalai; Jain, Sushil K

2016-03-01

Adiponectin is an anti-diabetic and anti-atherogenic adipokine; its plasma levels are decreased in obesity, insulin resistance, and type 2 diabetes. An adiponectin-interacting protein named disulfide bond A-like protein (DsbA-L) plays an important role in the assembly of adiponectin. This study examined the hypothesis that L-cysteine (LC) regulates glucose homeostasis through the DsbA-L upregulation and synthesis and secretion of adiponectin in diabetes. 3T3L1 adipocytes were treated with LC (250 and 500 µM, 2 h) and high glucose (HG, 25 mM, 20 h). Results showed that LC supplementation significantly (p < 0.05) upregulated the DsbA-L, adiponectin, and GLUT-4 protein expression and glucose utilization in HG-treated adipocytes. LC supplementation significantly (p < 0.05) promoted the secretion of total and HMW adiponectin secretion in HG-treated adipocytes. In addition, LC significantly (p < 0.05) decreased ROS production and MCP-1 secretion in HG-treated cells. We further investigated whether MCP-1 has any role of LC on DsbA-L expression and adiponectin levels in 3T3-L1 cells. Treatment with LC prevented the decrease in DsbA-L, adiponectin, and GLUT-4 expression in 3T3L1 adipocyte cells exposed to MCP-1. Thus, this study demonstrates that DsbA-L and adiponectin upregulation mediates the beneficial effects of LC on glucose utilization by inhibiting MCP-1 secretion in adipocytes and provides a novel mechanism by which LC supplementation can improve insulin sensitivity in diabetes.

The impact of obesity and adiponectin signaling in patients with renal cell carcinoma: A potential mechanism for the "obesity paradox".

PubMed

Ito, Ryuichi; Narita, Shintaro; Huang, Mingguo; Nara, Taketoshi; Numakura, Kazuyuki; Takayama, Koichiro; Tsuruta, Hiroshi; Maeno, Atsushi; Saito, Mitsuru; Inoue, Takamitsu; Tsuchiya, Norihiko; Satoh, Shigeru; Habuchi, Tomonori

2017-01-01

Although obesity increases the risk of renal cell carcinoma (RCC), obese patients with RCC experience longer survival than non-obese patients. However, the mechanism of this "obesity paradox" is unknown. We examined the impact of preoperative BMI, serum total adiponectin (sAd) level, total adiponectin secretion from perinephric adipose tissue, and intratumoral expression of adiponectin receptors on RCC aggressiveness and survival. We also investigated the mechanism underlying enhanced cancer aggressiveness in RCC cells stimulated with exogenous adiponectin. Overweight and obese patients had significantly lower grade cancers than normal patients in all patients and in those without metastasis (p = 0.003 and p = 0.027, respectively). Cancer-specific survival was significantly longer in overweight and obese patients than in normal patients in all patients (p = 0.035). There was a weak inverse correlation between sAd level and BMI in RCC patients (r = -0.344, p = 0.002). Tumor size was slightly correlated with sAd level, and high sAd was significantly associated with poor overall survival rates in patients with non-metastatic RCC (p = 0.035). Adiponectin levels in perinephric adipose tissue and intratumoral AdipoR1/R2 expression were not correlated with RCC aggressiveness or survival. Proliferation significantly increased in 786-O and Caki-2 cells exposed to exogenous adiponectin, whereas cell invasion and migration were unaffected. In addition, exogenous adiponectin significantly inhibited starvation- and metformin-induced apoptosis, and up-regulated p-AMPK and Bcl-xL levels. In summary, low BMI and high adiponectin levels are associated with aggressive cell behaviors and poor survival in surgically-treated RCC patients. The effects of adiponectin on proliferation and apoptosis might underlie the "obesity paradox" of RCC.

Temporal and Molecular Analyses of Cardiac Extracellular Matrix Remodeling following Pressure Overload in Adiponectin Deficient Mice

PubMed Central

Dadson, Keith; Turdi, Subat; Boo, Stellar; Hinz, Boris; Sweeney, Gary

2015-01-01

Adiponectin, circulating levels of which are reduced in obesity and diabetes, mediates cardiac extracellular matrix (ECM) remodeling in response to pressure overload (PO). Here, we performed a detailed temporal analysis of progressive cardiac ECM remodelling in adiponectin knockout (AdKO) and wild-type (WT) mice at 3 days and 1, 2, 3 and 4 weeks following the induction of mild PO via minimally invasive transverse aortic banding. We first observed that myocardial adiponectin gene expression was reduced after 4 weeks of PO, whereas increased adiponectin levels were detected in cardiac homogenates at this time despite decreased circulating levels of adiponectin. Scanning electron microscopy and Masson’s trichrome staining showed collagen accumulation increased in response to 2 and 4 weeks of PO in WT mice, while fibrosis in AdKO mice was notably absent after 2 weeks but highly apparent after 4 weeks of PO. Time and intensity of fibroblast appearance after PO was not significantly different between AdKO and WT animals. Gene array analysis indicated that MMP2, TIMP2, collagen 1α1 and collagen 1α3 were induced after 2 weeks of PO in WT but not AdKO mice. After 4 weeks MMP8 was induced in both genotypes, MMP9 only in WT mice and MMP1α only in AdKO mice. Direct stimulation of primary cardiac fibroblasts with adiponectin induced a transient increase in total collagen detected by picrosirius red staining and collagen III levels synthesis, as well as enhanced MMP2 activity detected via gelatin zymography. Adiponectin also enhanced fibroblast migration and attenuated angiotensin-II induced differentiation to a myofibroblast phenotype. In conclusion, these data indicate that increased myocardial bioavailability of adiponectin mediates ECM remodeling following PO and that adiponectin deficiency delays these effects. PMID:25910275

Adiponectin is required for maintaining normal body temperature in a cold environment.

PubMed

Wei, Qiong; Lee, Jong Han; Wang, Hongying; Bongmba, Odelia Y N; Wu, Chia-Shan; Pradhan, Geetali; Sun, Zilin; Chew, Lindsey; Bajaj, Mandeep; Chan, Lawrence; Chapkin, Robert S; Chen, Miao-Hsueh; Sun, Yuxiang

2017-10-23

Thermogenic impairment promotes obesity and insulin resistance. Adiponectin is an important regulator of energy homeostasis. While many beneficial metabolic effects of adiponectin resemble that of activated thermogenesis, the role of adiponectin in thermogenesis is not clear. In this study, we investigated the role of adiponectin in thermogenesis using adiponectin-null mice (Adipoq -/- ). Body composition was measured using EchoMRI. Metabolic parameters were determined by indirect calorimetry. Insulin sensitivity was evaluated by glucose- and insulin- tolerance tests. Core body temperature was measured by a TH-8 temperature monitoring system. Gene expression was assessed by real-time PCR and protein levels were analyzed by Western blotting and immunohistochemistry. The mitochondrial density of brown adipose tissue was quantified by calculating the ratio of mtDNA:total nuclear DNA. Under normal housing temperature of 24 °C and ad libitum feeding condition, the body weight, body composition, and metabolic profile of Adipoq -/- mice were unchanged. Under fasting condition, Adipoq -/- mice exhibited reduced energy expenditure. Conversely, under cold exposure, Adipoq -/- mice exhibited reduced body temperature, and the expression of thermogenic regulatory genes was significantly reduced in brown adipose tissue (BAT) and subcutaneous white adipose tissue (WAT). Moreover, we observed that mitochondrial content was reduced in BAT and subcutaneous WAT, and the expression of mitochondrial fusion genes was decreased in BAT of Adipoq -/- mice, suggesting that adiponectin ablation diminishes mitochondrial biogenesis and altered mitochondrial dynamics. Our study further revealed that adiponectin deletion suppresses adrenergic activation, and down-regulates β3-adrenergic receptor, insulin signaling, and the AMPK-SIRT1 pathway in BAT. Our findings demonstrate that adiponectin is an essential regulator of thermogenesis, and adiponectin is required for maintaining body temperature under cold exposure.

Influence of adiponectin gene polymorphism SNP276 (G/T) on adiponectin in response to exercise training.

PubMed

Huang, Hu; Tada Iida, Kaoruko; Murakami, Haruka; Saito, Yoko; Otsuki, Takeshi; Iemitsu, Motoyuki; Maeda, Seiji; Sone, Hirohito; Kuno, Shinya; Ajisaka, Ryuichi

2007-12-01

Adiponectin is an adipocytokine that is involved in insulin sensitivity. The adiponectin gene contains a single nucleotide polymorphism (SNP) at position 276 (G/T). The GG genotype of SNP276 (G/T) is associated with lower plasma adiponectin levels and a higher insulin resistance index. Therefore, we examined the influence of SNP276 (G/T) on the plasma level of adiponectin in response to exercise training. Thirty healthy Japanese (M12/F18; 56 to 79 years old) performed both resistance and endurance training, 5 times a week for 6 months. The work rate per kg of weight at double-product break-point (DPBP) was measured. Blood samples were obtained before and after the experiment. Plasma concentrations of adiponectin, HbA1c, insulin, glucose, total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol, and triglyceride were measured. Genotypes of SNP276 were specified. Student's t-test for paired values and unpaired values was used. After the 6-month training period, the work rate per kg of weight at DPBP and the plasma HDL-cholesterol level were significantly improved (P<0.05), while no change was observed in the total plasma adiponectin level. However, the plasma adiponectin level in those with the GT + TT genotype had significantly increased (P<0.05). Additionally, the degree of the decrease in the HOMA-R level was significantly greater in the subjects with the GT + TT genotype than those with the GG genotype (p<0.05). Our results suggest that subjects with the genotype GT + TT at SNP276 (G/T) have a greater adiponectin-related response to exercise training than those with the GG genotype.

Tumor necrosis factor- α, adiponectin and their ratio in gestational diabetes mellitus

PubMed Central

Khosrowbeygi, Ali; Rezvanfar, Mohammad Reza; Ahmadvand, Hassan

2018-01-01

Background: It has been suggested that inflammation might be implicated in the gestational diabetes mellitus (GDM) complications, including insulin resistance. The aims of the current study were to explore maternal circulating values of TNF-α, adiponectin and the adiponectin/TNF-α ratio in women with GDM compared with normal pregnancy and their relationships with metabolic syndrome biomarkers. Methods: Forty women with GDM and 40 normal pregnant women were included in the study. Commercially available enzyme-linked immunosorbent assay methods were used to measure serum levels of TNF-α and total adiponectin. Results: Women with GDM had higher values of TNF-α (225.08±27.35 vs 115.68±12.64 pg/ml, p<0.001) and lower values of adiponectin (4.50±0.38 vs 6.37±0.59 µg/ml, p=0.003) and the adiponectin/TNF-α ratio (4.31±0.05 vs 4.80±0.07, P<0.001) than normal pregnant women. The adiponectin/TNF-α ratio showed negative correlations with insulin resistance (r=-0.68, p<0.001) and triglyceride (r=-0.39, p=0.014) and a positive correlation with insulin sensitivity (r=0.69, p<0.001). Multiple linear regression analysis showed that values of the adiponectin /TNF-α ratio were independently associated with insulin resistance. Binary logistic regression analysis showed that GDM was negatively associated with adiponectin /TNF-α ratio. Conclusions: In summary, the adiponectin/TNF-α ratio decreased significantly in GDM compared with normal pregnancy. The ratio might be an informative biomarker for assessment of pregnant women at high risk of insulin resistance and dyslipidemia and for diagnosis and therapeutic monitoring aims in GDM. PMID:29387323

The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance

PubMed Central

Chang, Ming-Ling; Kuo, Chia-Jung; Pao, Li-Heng; Hsu, Chen-Ming; Chiu, Cheng-Tang

2017-01-01

ABSTRACT Background: The evolution of the relationship between adiponectin and insulin sensitivity in hepatitis C virus (HCV) patients during viral clearance is unclear and warrants investigation. Methods: A prospective study including 747 consecutive chronic hepatitis C (CHC) patients, of whom 546 had completed a course of anti-HCV therapy and underwent pre-, peri- and post-therapy surveys for anthropomorphic, viral, metabolic and hepatic profiles and adiponectin levels, was conducted in a tertiary care center. Results: Multivariate analyses indicated associations of sex, triglyceride levels and hepatic steatosis with adiponectin levels and of triglyceride levels and interferon λ3 (IFNL3) genotype with homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels before anti-HCV therapy. In patients with a sustained virological response (SVR; n = 455), at 24 weeks post-therapy, sex, BMI, aspartate aminotransferase to platelet ratio index (APRI), HOMA-IR and steatosis were associated with adiponectin levels, and IFNL3 genotype was associated with HOMA-IR levels. GEE analysis demonstrated that SVR affected longitudinal trends in adiponectin levels. Compared with pre-therapy levels, adiponectin and APRI levels decreased 24 weeks post-therapy in SVR patients, regardless of baseline insulin resistance (IR). However, HOMA-IR levels decreased in SVR patients with baseline IR but increased in those without baseline IR. Compared with controls, immunohistochemical studies showed that pre-therapy CHC patients had higher hepatic adiponectin expression associated with hepatic fibrosis. Conclusions: During HCV infection, adiponectin may affect insulin sensitivity through triglycerides. After viral clearance, adiponectin levels were directly associated with insulin sensitivity and decreased upon improved hepatic fibrosis; with a link to the IFNL3 genotype, insulin sensitivity improved only in patients with baseline IR. PMID:28267407

Adiponectin changes in relation to the macronutrient composition of a weight-loss diet.

PubMed

Summer, Suzanne S; Brehm, Bonnie J; Benoit, Stephen C; D'Alessio, David A

2011-11-01

Adiponectin is an adipose-derived protein with beneficial metabolic effects. Low adiponectin is associated with obesity and related diseases. Significant weight loss increases adiponectin, reducing disease risk. This study compared the effects of two weight-loss diets with different macronutrient compositions on adiponectin. Eighty-one obese women in two cohorts were randomized to a low-fat (LF) or a low-carbohydrate (LC) diet. All subjects underwent equivalent weight-loss intervention, with weight and other measures assessed at baseline and after 6 (cohort I) or 4 (cohort II) months. Body fat was measured by dual energy X-ray absorptiometry. Adiponectin was measured by radioimmunoassay. Diet intake was assessed using 24-h recalls and 3-day diet records. Data were analyzed via t-tests and repeated-measures factorial ANOVA using time, diet, and replicate (cohort I vs. cohort II) as factors. Age, weight, body fat, BMI, adiponectin, and diet were similar at baseline. Following intervention, macronutrient composition of the diet was vastly different between the groups, reflecting the assigned diet. Both groups lost weight and body fat (P < 0.001), with effect in LC dieters greater than LF dieters (-9.1 kg vs. -4.97 kg weight, P < 0.05 and -5.45 kg vs. -2.62 kg fat, P < 0.001). Adiponectin increased in the LC (+1.92 mcg/ml, P < 0.01), but not the LF (+0.86 mcg/ml, P = 0.81), group. There was no correlation between weight loss and increase in adiponectin. These results confirm that diet-induced loss of weight and body fat is associated with increased adiponectin concentrations. This effect is evident with weight loss of 10% or more, and may be greater with LC diets.

Association between ADIPOQ SNPs with plasma adiponectin and glucose homeostasis and adiposity phenotypes in the IRAS Family Study.

PubMed

An, S Sandy; Hanley, Anthony J G; Ziegler, Julie T; Brown, W Mark; Haffner, Steven M; Norris, Jill M; Rotter, Jerome I; Guo, Xiuqing; Chen, Y-D Ida; Wagenknecht, Lynne E; Langefeld, Carl D; Bowden, Donald W; Palmer, Nicholette D

2012-12-01

Adiponectin is an adipocytokine associated with a variety of metabolic traits. These associations in human studies, in conjunction with functional studies in model systems, have implicated adiponectin in multiple metabolic processes. We hypothesize that genetic variants associated with plasma adiponectin would also be associated with glucose homeostasis and adiposity phenotypes. The Insulin Resistance Atherosclerosis Family Study was designed to identify the genetic and environmental basis of insulin resistance and adiposity in the Hispanic- (n=1,424) and African-American (n=604) population. High quality metabolic phenotypes, e.g. insulin sensitivity (S(I)), acute insulin response (AIR), disposition index (DI), fasting glucose, body mass index (BMI), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and waist circumference, were explored. Based on association analysis of more than 40 genetic polymorphisms in the adiponectin gene (ADIPOQ), we found no consistent association of ADIPOQ variants with plasma adiponectin levels and adiposity phenotypes. However, there were two promoter variants, rs17300539 and rs822387, associated with plasma adiponectin levels (P=0.0079 and 0.021, respectively) in the Hispanic-American cohort that were also associated with S(I) (P=0.0067 and 0.013, respectively). In contrast, there was only a single promoter SNP, rs17300539, associated with plasma adiponectin levels (P=0.0018) and fasting glucose (P=0.042) in the African-American cohort. Strikingly, high impact coding variants did not show evidence of association. The lack of consistent patterns of association between variants, adiponectin levels, glucose homeostasis, and adiposity phenotypes suggests a reassessment of the influence of adiponectin in these pathways. Copyright © 2012 Elsevier Inc. All rights reserved.

11β-HSD1 reduces metabolic efficacy and adiponectin synthesis in hypertrophic adipocytes.

PubMed

Koh, Eun Hee; Kim, Ah-Ram; Kim, Hyunshik; Kim, Jin Hee; Park, Hye-Sun; Ko, Myoung Seok; Kim, Mi-Ok; Kim, Hyuk-Joong; Kim, Bum Joong; Yoo, Hyun Ju; Kim, Su Jung; Oh, Jin Sun; Woo, Chang-Yun; Jang, Jung Eun; Leem, Jaechan; Cho, Myung Hwan; Lee, Ki-Up

2015-06-01

Mitochondrial dysfunction in hypertrophic adipocytes can reduce adiponectin synthesis. We investigated whether 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression is increased in hypertrophic adipocytes and whether this is responsible for mitochondrial dysfunction and reduced adiponectin synthesis. Differentiated 3T3L1 adipocytes were cultured for up to 21 days. The effect of AZD6925, a selective 11β-HSD1 inhibitor, on metabolism was examined. db/db mice were administered 600 mg/kg AZD6925 daily for 4 weeks via gastric lavage. Mitochondrial DNA (mtDNA) content, mRNA expression levels of 11 β -H sd1 and mitochondrial biogenesis factors, adiponectin synthesis, fatty acid oxidation (FAO), oxygen consumption rate and glycolysis were measured. Adipocyte hypertrophy in 3T3L1 cells exposed to a long duration of culture was associated with increased 11 β -Hsd1 mRNA expression and reduced mtDNA content, mitochondrial biogenesis factor expression and adiponectin synthesis. These cells displayed reduced mitochondrial respiration and increased glycolysis. Treatment of these cells with AZD6925 increased adiponectin synthesis and mitochondrial respiration. Inhibition of FAO by etomoxir blocked the AZD6925-induced increase in adiponectin synthesis, indicating that 11β-HSD1-mediated reductions in FAO are responsible for the reduction in adiponectin synthesis. The expression level of 11 β -Hsd1 was higher in adipose tissues of db/db mice. Administration of AZD6925 to db/db mice increased the plasma adiponectin level and adipose tissue FAO. In conclusion, increased 11β-HSD1 expression contributes to reduced mitochondrial respiration and adiponectin synthesis in hypertrophic adipocytes. © 2015 Society for Endocrinology.

THE INFLUENCE OF BODY-MASS INDEX AND RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM ACTIVITY ON THE RELATIONSHIP BETWEEN 25-HYDROXYVITAMIN D AND ADIPONECTIN IN CAUCASIAN MEN

PubMed Central

Vaidya, Anand; Forman, John P.; Underwood, Patricia C.; Hopkins, Paul N.; Williams, Gordon H.; Pojoga, Luminita H.; Williams, Jonathan S.

2011-01-01

Objective Prior studies have suggested that circulating adiponectin concentrations are associated positively with vitamin D and negatively with body-mass index (BMI), but have not accounted for the influence of the renin-angiotensin-aldosterone system (RAAS) in this relationship. This is particularly relevant because increased RAAS activity is associated with obesity and is known to lower adiponectin levels. We evaluated the association between adiponectin and 25-hydroxyvitamin D (25[OH]D) after controlling RAAS activity with dietary sodium equilibration, and also evaluated whether this relationship was influenced by BMI. Design Cross-sectional study of 115 hypertensive Caucasian men from the HyperPATH Consortium. Methods To manipulate RAAS activity, all subjects underwent one week of high sodium (HS) diet to suppress RAAS, and one week of low sodium (LS) diet to stimulate RAAS. Linear regression was used to evaluate the association between adiponectin and 25(OH)D, and the effect of BMI on this relationship, in each dietary condition. Results Adiponectin was higher on HS, where circulating RAAS activity was low, when compared to LS (HS=2.9 versus LS=2.4 µg/mL, p<0.0001). 25(OH)D levels were positively associated with adiponectin, and BMI was a statistically significant effect modifier of the relationship between 25(OH)D and adiponectin on both diets (p-interaction < 0.01 between BMI and 25[OH]D). Conclusions Higher 25(OH)D concentrations were independently associated with higher adiponectin levels, particularly when BMI was high. Dietary sodium balance and circulating RAAS activity did not appear to affect this relationship. Future studies should explore whether vitamin D supplementation increases adiponectin levels in obesity. PMID:21402748

Monomeric adiponectin modulates nitric oxide release and calcium movements in porcine aortic endothelial cells in normal/high glucose conditions.

PubMed

Grossini, Elena; Farruggio, Serena; Qoqaiche, Fatima; Raina, Giulia; Camillo, Lara; Sigaudo, Lorenzo; Mary, David; Surico, Nicola; Surico, Daniela

2016-09-15

Perivascular adipose tissue can be involved in the process of cardiovascular pathology through the release of adipokines, namely adiponectins. Monomeric adiponectin has been shown to increase coronary blood flow in anesthetized pigs through increased nitric oxide (NO) release and the involvement of adiponectin receptor 1 (AdipoR1). The present study was therefore planned to examine the effects of monomeric adiponectin on NO release and Ca(2+) transients in porcine aortic endothelial cells (PAEs) in normal/high glucose conditions and the related mechanisms. PAEs were treated with monomeric adiponectin alone or in the presence of intracellular kinases blocker, AdipoR1 and Ca(2+)-ATPase pump inhibitors. The role of Na(+)/Ca(2+) exchanger was examined in experiments performed in zero Na(+) medium. NO release and intracellular Ca(2+) were measured through specific probes. In PAE cultured in normal glucose conditions, monomeric adiponectin elevated NO production and [Ca(2+)]c. Similar effects were observed in high glucose conditions, although the response was lower and not transient. The Ca(2+) mobilized by monomeric adiponectin originated from an intracellular pool thapsigargin- and ATP-sensitive and from the extracellular space. Moreover, the effects of monomeric adiponectin were prevented by kinase blockers and AdipoR1 inhibitor. Finally, in normal glucose condition, a role for Na(+)/Ca(2+) exchanger and Ca(2+)-ATPase pump in restoring Ca(2+) was found. Our results add new information about the control of endothelial function elicited by monomeric adiponectin, which would be achieved by modulation of NO release and Ca(2+) transients. A signalling related to Akt, ERK1/2 and p38MAPK downstream AdipoR1 would be involved. Copyright © 2016 Elsevier Inc. All rights reserved.

Coffee consumption but not green tea consumption is associated with adiponectin levels in Japanese males.

PubMed

Imatoh, T; Tanihara, S; Miyazaki, M; Momose, Y; Uryu, Y; Une, H

2011-06-01

Coffee is among the most widely consumed beverages in the world. Numerous epidemiological studies have reported a significant inverse association between coffee consumption and risk of type 2 diabetes mellitus, but the underlying mechanisms are still not fully understood. Therefore, we conducted an epidemiological study to clarify the relationship between coffee consumption and adiponectin levels in Japanese males. We also evaluated whether green tea consumption affected adiponectin levels. We carried out a cross-sectional study. The subjects were 665 male employees in Japan. Coffee consumption was assessed, using a self-administered questionnaire, as the number of times per week and cups per day respondents drank, and subjects were grouped into four levels (non, 1-5 times/week, 1-2 cups/day and ≥3 cups/day). The means of adiponectin levels were positively associated with coffee consumption. A dose-response relationship was found between coffee consumption and circulating adiponectin levels. The relationship remained significant after adjustment for potential confounding factors (P for trend <0.05). However, green tea consumption was not significantly associated with adiponectin levels (P for trend = 0.90). We not only revealed that habitual coffee consumption is associated with higher adiponectin levels in Japanese males but also found a dose-dependent association between coffee consumption and adiponectin levels. Therefore, our study suggested that coffee components might play an important role in the elevation of adiponectin level.

Gene-environment interaction between adiponectin gene polymorphisms and environmental factors on the risk of diabetic retinopathy.

PubMed

Li, Yuan; Wu, Qun Hong; Jiao, Ming Li; Fan, Xiao Hong; Hu, Quan; Hao, Yan Hua; Liu, Ruo Hong; Zhang, Wei; Cui, Yu; Han, Li Yuan

2015-01-01

To evaluate whether the adiponectin gene is associated with diabetic retinopathy (DR) risk and interaction with environmental factors modifies the DR risk, and to investigate the relationship between serum adiponectin levels and DR. Four adiponectin polymorphisms were evaluated in 372 DR cases and 145 controls. Differences in environmental factors between cases and controls were evaluated by unconditional logistic regression analysis. The model-free multifactor dimensionality reduction method and traditional multiple regression models were applied to explore interactions between the polymorphisms and environmental factors. Using the Bonferroni method, we found no significant associations between four adiponectin polymorphisms and DR susceptibility. Multivariate logistic regression found that physical activity played a protective role in the progress of DR, whereas family history of diabetes (odds ratio 1.75) and insulin therapy (odds ratio 1.78) were associated with an increased risk for DR. The interaction between the C-11377 G (rs266729) polymorphism and insulin therapy might be associated with DR risk. Family history of diabetes combined with insulin therapy also increased the risk of DR. No adiponectin gene polymorphisms influenced the serum adiponectin levels. Serum adiponectin levels did not differ between the DR group and non-DR group. No significant association was identified between four adiponectin polymorphisms and DR susceptibility after stringent Bonferroni correction. The interaction between C-11377G (rs266729) polymorphism and insulin therapy, as well as the interaction between family history of diabetes and insulin therapy, might be associated with DR susceptibility.

Essential roles of insulin, AMPK signaling and lysyl and prolyl hydroxylases in the biosynthesis and multimerization of adiponectin.

PubMed

Zhang, Lin; Li, Ming-Ming; Corcoran, Marie; Zhang, Shaoping; Cooper, Garth J S

2015-01-05

Post-translational modifications (PTMs) of the adiponectin molecule are essential for its full bioactivity, and defects in PTMs leading to its defective production and multimerization have been linked to the mechanisms of insulin resistance, obesity, and type-2 diabetes. Here we observed that, in differentiated 3T3-L1 adipocytes, decreased insulin signaling caused by blocking of insulin receptors (InsR) with an anti-InsR blocking antibody, increased rates of adiponectin secretion, whereas concomitant elevations in insulin levels counteracted this effect. Adenosine monophosphate-activated protein kinase (AMPK) signaling regulated adiponectin production by modulating the expression of adiponectin receptors, the secretion of adiponectin, and eventually the expression of adiponectin itself. We found that lysyl hydroxylases (LHs) and prolyl hydroxylases (PHs) were expressed in white-adipose tissue of ob/ob mice, wherein LH3 levels were increased compared with controls. In differentiated 3T3-L1 adipocytes, both non-specific inhibition of LHs and PHs by dipyridyl, and specific inhibition of LHs by minoxidil and of P4H with ethyl-3,4-dihydroxybenzoate, caused significant suppression of adiponectin production, more particularly of the higher-order isoforms. Transient gene knock-down of LH3 (Plod3) caused a suppressive effect, especially on the high molecular-weight (HMW) isoforms. These data indicate that PHs and LHs are both required for physiological adiponectin production and in particular are essential for the formation/secretion of the HMW isoforms. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

PKA/AMPK signaling in relation to adiponectin's antiproliferative effect on multiple myeloma cells.

PubMed

Medina, E A; Oberheu, K; Polusani, S R; Ortega, V; Velagaleti, G V N; Oyajobi, B O

2014-10-01

Obesity increases the risk of developing multiple myeloma (MM). Adiponectin is a cytokine produced by adipocytes, but paradoxically decreased in obesity, that has been implicated in MM progression. Herein, we evaluated how prolonged exposure to adiponectin affected the survival of MM cells as well as putative signaling mechanisms. Adiponectin activates protein kinase A (PKA), which leads to decreased AKT activity and increased AMP-activated protein kinase (AMPK) activation. AMPK, in turn, induces cell cycle arrest and apoptosis. Adiponectin-induced apoptosis may be mediated, at least in part, by the PKA/AMPK-dependent decline in the expression of the enzyme acetyl-CoA-carboxylase (ACC), which is essential to lipogenesis. Supplementation with palmitic acid, the preliminary end product of fatty acid synthesis, rescues MM cells from adiponectin-induced apoptosis. Furthermore, 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), an ACC inhibitor, exhibited potent antiproliferative effects on MM cells that could also be inhibited by fatty acid supplementation. Thus, adiponectin's ability to reduce survival of MM cells appears to be mediated through its ability to suppress lipogenesis. Our findings suggest that PKA/AMPK pathway activators, or inhibitors of ACC, may be useful adjuvants to treat MM. Moreover, the antimyeloma effect of adiponectin supports the concept that hypoadiponectinemia, as occurs in obesity, promotes MM tumor progression.

Urinary adiponectin and albuminuria in non-diabetic hypertensive patients: an analysis of the ESPECIAL trial.

PubMed

Han, Seung Seok; Bae, Eunjin; Ahn, Shin Young; Kim, Sejoong; Park, Jung Hwan; Shin, Sung Joon; Lee, Sang Ho; Choi, Bum Soon; Chin, Ho Jun; Lim, Chun Soo; Kim, Suhnggwon; Kim, Dong Ki

2015-08-01

Although adiponectin levels have been reported to be correlated with albuminuria, this issue remains unresolved in non-diabetic hypertensive subjects, particularly when urinary adiponectin is considered. Urinary adiponectin levels were examined using an enzyme-linked immunosorbent assay in 229 participants. who used olmesartan as a hypertensive agent. Their albuminuria levels were measured for 16 weeks after randomization and initiation of conventional or intensive diet education. Linear or logistic regression models were applied, as appropriate, to explore the relationship with albuminuria itself or its response after the intervention. Urinary adiponectin levels were positively related to baseline albuminuria level (r = 0.529). After adjusting for several covariates, the adiponectin level was associated with the albuminuria level (β = 0.446). Among the 159 subjects with baseline macroalbuminuria, the risk of consistent macroalbuminuria (> 300 mg/day) at 16 weeks was higher in the 3(rd) tertile of adiponectin than in the 1(st) tertile (odds ratio = 6.9), despite diet education. In contrast, among all subjects, the frequency of the normoalbuminuria achievement (< 30 mg/day) at 16 weeks was higher in the 1(st) tertile than in the 3(rd) tertile (odds ratio = 13.0). Urinary adiponectin may be a useful biomarker for albuminuria or its response after treatment in non-diabetic hypertensive patients.

UV-induced inhibition of adipokine production in subcutaneous fat aggravates dermal matrix degradation in human skin.

PubMed

Kim, Eun Ju; Kim, Yeon Kyung; Kim, Min-Kyoung; Kim, Sungsoo; Kim, Jin Yong; Lee, Dong Hun; Chung, Jin Ho

2016-05-10

Ultraviolet (UV) exposure to the human skin reduces triglycerides contents and lipid synthesis in the subcutaneous (SC) fat. Because adiponectin and leptin are the most abundant adipokines from the SC fat, we aim to investigate how they interact with UV exposure and skin aging. The expressions of adiponectin and leptin were significantly decreased in SC fat of sun-exposed forearm skin, in comparison with that of sun-protected buttock skin of the same elderly individuals, indicating that chronic UV exposure decreases both adipokines. Acute UV irradiation also decreased the expressions of adiponectin and leptin in SC fat. The expressions of adiponectin receptor 1/2 and leptin receptor were significantly decreased in the dermis as well as in SC fat. Moreover, while exogenous adiponectin and leptin administration prevented UV- and TNF-α induced matrix metalloproteinase (MMP)-1 expression, they also increased UV- and TNF-α induced reduction of type 1 procollagen production. Silencing of adiponectin, leptin or their receptors led to an increased MMP-1 and a decreased type 1 procollagen expression, which was reversed by treatment with recombinant human adiponectin or leptin. In conclusion, UV exposure decreases the expression of adiponectin and leptin, leading to the exacerbation of photoaging by stimulating MMP-1 expression and inhibiting procollagen synthesis.

Characteristics and potential functions of human milk adiponectin.

PubMed

Newburg, David S; Woo, Jessica G; Morrow, Ardythe L

2010-02-01

Adiponectin is a protein hormone produced by adipose tissue, whose circulating levels are inversely related to adiposity and inflammation. Adiponectin circulates as oligomers, from the low-molecular-weight trimer to the high-molecular-weight octodecamer (18 mer). Each oligomer has distinct biological activities, which include enhancement of insulin sensitivity and metabolic control and suppression of inflammation. Adiponectin occurs in human milk at higher concentrations than leptin. The adiponectin in human milk is almost entirely of the high-molecular-weight form, the form with the highest activity in controlling many types of metabolic processes. Human adiponectin fed to infant mice is transported across the intestinal mucosa into the serum. An inverse relationship between adiponectin levels in milk and adiposity (weight-for-height) of the breast-fed infant was observed and could be due to modulation of infant metabolism by milk adiponectin and may be related to the observed protection against obesity by breast-feeding. Human milk may be a medium whereby the hormonal milieu (in response to internal factors and the environment) of the mother can be used to communicate with the breast-fed infant to modify infant metabolic processes. Transmission of information from mother to infant through milk may allow adaptation to fluctuating environmental conditions. Copyright 2010 Mosby, Inc. All rights reserved.

Association of adiponectin gene polymorphism (+T45G) with acute coronary syndrome and circulating adiponectin levels.

PubMed

Rizk, Nasser M; El-Menyar, Ayman; Marei, Isra; Sameer, Maha; Musad, Tasneem; Younis, Dima; Farag, Fathi; Basem, Nora; Al-Ali, Khalid; Al Suwaidi, Jassim

2013-05-01

We investigated the association of adiponectin gene polymorphisms (+T45G and +G276T) and adiponectin levels with acute coronary syndrome (ACS) among Arabs in Qatar. A case-control study was performed in 142 Arab patients with ACS and 122 controls. Genotypes were determined using TaqMan real-time polymerase chain reaction assay. The TT, TG, and GG genotype frequencies of the T45G variant were significantly different among cases and controls (P = .023) but not significant for G276T genotypic frequencies. It was found that only the +45G allele was significantly associated with 3-fold increased risk of ACS (odds ratio = 2.77; 1.03-6.96; P = .043) among patients, using the genetic recessive model. Carriers of GG alleles had significantly lower adiponectin levels compared to TT/TG carriers of T45G in patients with ACS. The present study suggests that only T45G single-nucleotide polymorphism in the adiponectin gene is associated with higher odds for ACS events and has an effect on serum adiponectin levels among Arab populations.

IGFBP-3, hypoxia and TNF-{alpha} inhibit adiponectin transcription

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zappala, Giovanna, E-mail: zappalag@mail.nih.gov; Rechler, Matthew M.; Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD

2009-05-15

The thiazolidinedione rosiglitazone, an agonist ligand for the nuclear receptor PPAR-{gamma}, improves insulin sensitivity in part by stimulating transcription of the insulin-sensitizing adipokine adiponectin. It activates PPAR-{gamma}-RXR-{alpha} heterodimers bound to PPAR-{gamma} response elements in the adiponectin promoter. Rosiglitazone-stimulated adiponectin protein synthesis in 3T3-L1 mouse adipocytes has been shown to be inhibited by IGFBP-3, which can be induced by hypoxia and the proinflammatory cytokine, TNF-{alpha}, two inhibitors of adiponectin transcription. The present study demonstrates that IGFBP-3, the hypoxia-mimetic agent cobalt chloride, and TNF-{alpha} inhibit rosiglitazone-induced adiponectin transcription in mouse embryo fibroblasts that stably express PPAR-{gamma}2. Native IGFBP-3 can bind RXR-{alpha} andmore » inhibited rosiglitazone stimulated promoter activity, whereas an IGFBP-3 mutant that does not bind RXR-{alpha} did not. These results suggest that IGFBP-3 may mediate the inhibition of adiponectin transcription by hypoxia and TNF-{alpha}, and that IGFBP-3 binding to RXR-{alpha} may be required for the observed inhibition.« less

Effects of Alpha-Lipoic Acid Supplementation on Plasma Adiponectin Levels and Some Metabolic Risk Factors in Patients with Schizophrenia.

PubMed

Vidović, Bojana; Milovanović, Srđan; Stefanović, Aleksandra; Kotur-Stevuljević, Jelena; Takić, Marija; Debeljak-Martačić, Jasmina; Pantović, Maja; Đorđević, Brižita

2017-01-01

Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and anti-inflammatory properties and is suggested to be a biomarker of metabolic disturbances. The aim of this study was to investigate the effects of alpha-lipoic acid (ALA) on plasma adiponectin and some metabolic risk factors in patients with schizophrenia. The plasma adipokine levels (adiponectin and leptin), routine biochemical and anthropometric parameters, markers of oxidative stress, and the serum phospholipid fatty acid profile in eighteen schizophrenic patients at baseline, in the middle, and at the end of a 3-month long supplementation period with ALA (500 mg daily) were determined. A significant increase in the plasma adiponectin concentrations, as well as a decrease in fasting glucose and aspartate aminotransferase activity (AST), was found. Baseline AST activity was independently correlated with the adiponectin concentrations. Our data show that ALA can improve plasma adiponectin levels and may play a potential role in the treatment of metabolic risk factor in patients with schizophrenia. Future randomized controlled trials are needed to confirm these preliminary investigations.

Early Whole Blood for Patients Requiring Massive Transfusion after Major Trauma. Addendum

DTIC Science & Technology

2013-10-01

process of determining which of the 45 patients had an abdominal CT. Measure serum (adipokines, leptin, adiponectin, and ghrelin ). We obtained serial...samples thru 24 hours on 60 patients and samples thru five days on 23 patients. We measured serum adiponectin, leptin, ghrelin , and resistin, and...adiponectin, leptin, and ghrelin were all lower in injured patients than in healthy volunteers at all timepoints. Adiponectin slowly decreased over time

Citrus auraptene acts as an agonist for PPARs and enhances adiponectin production and MCP-1 reduction in 3T3-L1 adipocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuroyanagi, Kayo; Kang, Min-Sook; Goto, Tsuyoshi

Citrus fruit compounds have many health-enhancing effects. In this study, using a luciferase ligand assay system, we showed that citrus auraptene activates peroxisome proliferator-activated receptor (PPAR)-{alpha} and PPAR{gamma}. Auraptene induced up-regulation of adiponectin expression and increased the ratio of the amount of high-molecular-weight multimers of adiponectin to the total adiponectin. In contrast, auraptene suppressed monocyte chemoattractant protein (MCP)-1 expression in 3T3-L1 adipocytes. Experiments using PPAR{gamma} antagonist demonstrated that these effects on regulation of adiponectin and MCP-1 expression were caused by PPAR{gamma} activations. The results indicate that auraptene activates PPAR{gamma} in adipocytes to control adipocytekines such as adiponectin and MCP-1 andmore » suggest that the consumption of citrus fruits, which contain auraptene can lead to a partial prevention of lipid and glucose metabolism abnormalities.« less

Adiponectin as a routine clinical biomarker.

PubMed

Kishida, Ken; Funahashi, Tohru; Shimomura, Iichiro

2014-01-01

Adiponectin is a protein synthesized and secreted predominantly by adipocytes into the peripheral blood. However, circulating adiponectin level is inversely related with body weight, especially visceral fat accumulation. The mechanism of this paradoxical relation remains obscure. Low circulating adiponectin concentrations (hypoadiponectinemia; <4 μg/mL) are associated with a variety of diseases, including dysmetabolism (type 2 diabetes, insulin resistance, hypertension, dyslipidemia, metabolic syndrome, hyperuricemia), atherosclerosis (coronary artery disease, stroke, peripheral artery disease), sleep apnea, non-alcoholic fatty liver disease, gastritis and gastro-esophageal reflux disease, inflammatory bowel diseases, pancreatitis, osteoporosis, and cancer (endometrial cancer, postmenopausal breast cancer, leukemia, colon cancer, gastric cancer, prostate cancer). On the other hand, hyperadiponectinemia is associated with cardiac, renal and pulmonary diseases. This review article focuses on the significance of adiponectin as a clinical biomarker of obesity-related diseases. Routine measurement of adiponectin in patients with lifestyle-related diseases is highly recommended. Copyright © 2013 Elsevier Ltd. All rights reserved.

Adiponectin Is Involved in Connective Tissue Growth Factor-Induced Proliferation, Migration and Overproduction of the Extracellular Matrix in Keloid Fibroblasts.

PubMed

Luo, Limin; Li, Jun; Liu, Han; Jian, Xiaoqing; Zou, Qianlei; Zhao, Qing; Le, Qu; Chen, Hongdou; Gao, Xinghua; He, Chundi

2017-05-12

Adiponectin, an adipocyte-derived hormone, exerts pleiotropic biological effects on metabolism, inflammation, vascular homeostasis, apoptosis and immunity. Recently, adiponectin has been suggested to attenuate the progression of human dermal fibrosis. Connective tissue growth factor (CTGF) is induced in keloids and is thought to be participated in the formation of keloid fibrosis. However, the roles played by adiponectin in keloids remain unclear. In this study, we explored the effects of adiponectin on CTGF-induced cell proliferation, migration and the deposition of extracellular matrix (ECM) and their associated intracellular signalling pathways in keloid fibroblasts (KFs). We also explored possible mechanisms of keloid pathogenesis. Primary fibroblast cultures were established from foreskin biopsies and skin biopsies from patients with keloids. The expression of adiponectin and adiponectin receptors (adipoRs) was evaluated by reverse transcription-PCR (RT-PCR), quantitative real-time RT-PCR, immunofluorescence staining, and immunohistochemical analysis. Next, KFs and normal dermal fibroblasts (NFs) were treated with CTGF in the presence or absence of adiponectin. A cell counting kit-8 (CCK-8) and the Transwell assay were used to examine cell proliferation and migration. The level of the collagen I, fibronectin (FN) and α-smooth muscle actin (α-SMA) mRNAs and proteins were determined by quantitative real-time RT-PCR and western blotting. The effects of RNA interference (RNAi) targeting the adipoR genes were detected. Phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase-protein kinase (PI3K-Akt) were examined by western blotting to further investigate the signalling pathways. Furthermore, inhibitors of signal transduction pathways were investigated. The expression levels of adiponectin and adipoRs were significantly decreased in keloids compared with those in normal skin tissue. Adiponectin suppressed the CTGF-induced KFs, but not NFs, proliferation, migration and ECM production. Moreover, adiponectin inhibited the phosphorylation of AMPK, p38 and extracellular-regulated kinase (ERK), but not that of Jun N-terminal kinase (JNK) or Akt, in CTGF-treated KFs. The activity of adiponectin-mediated signalling pathways was attenuated by small interfering RNAs (siRNAs) targeting adipoR1 (but not siRNAs targeting adipoR2, T-cadherin or calreticulin), AMPK (Compound C), p38 (SB203580) inhibitors, and mitogen-activated protein kinase kinase (MEK) inhibitor (PD98059). Based on our results, adiponectin suppresses CTGF-induced KFs proliferation, migration and ECM overproduction. One of the underlying mechanisms is the activation of the adipoR1, AMPK, p38, and ERK signalling pathways. Therefore, adiponectin may play an important role in the progression of keloids, suggesting a potential novel target for keloid treatment.

DHA increases adiponectin expression more effectively than EPA at relative low concentrations by regulating PPARγ and its phosphorylation at Ser273 in 3T3-L1 adipocytes.

PubMed

Song, Jia; Li, Cheng; Lv, Yushan; Zhang, Yi; Amakye, William Kwame; Mao, Limei

2017-01-01

Enhancing circulating adiponectin is considered as a potential approach for the prevention and treatment of non-communicable diseases (NCDs). Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were reported to increase adiponectin by previous studies using a mixture of them. However, their individual effects on adiponectin and the underlying mechanisms are still unclear. In the present study, we observed and compared the individual effect of DHA and EPA on adiponectin in 3T3-L1 adipocytes, and further tested whether DHA or EPA regulated adiponectin by peroxisome proliferator-activated receptor γ (PPARγ) and its phosphorylation at Ser273 to provide a plausible explanation for their distinct actions. Firstly, 3T3-L1 adipocytes were treated with different doses of DHA or EPA for 24 h. Secondly, 3T3-L1 adipocytes were treated with DHA or EPA in the presence or absence of GW9662. Thirdly, 3T3-L1 adipocytes were pretreated with DHA or EPA for 24 h, followed by being respectively co-incubated with tumor necrosis factor α (TNF-α) or roscovitine for another 2 h. Bovine serum albumin treatment served as the control. After treatments, cellular and secreted adiponectin, cellular PPARγ and its phosphorylation at Ser273 were determined. Compared with the control, DHA increased cellular and secreted adiponectin at 50 and 100 μmol/L, while EPA increased them at 100 and 200 μmol/L. Adiponectin expressions in DHA treated groups were significantly higher than those in EPA treated groups at 50 and 100 μmol/L. Both DHA and EPA enhanced PPARγ expression, but DHA was more effective. GW9662 blocked DHA- and EPA-induced increases in PPARγ as well as adiponectin. Remarkably, an opposite regulation of PPARγ phosphorylation was detected after fatty acids treatment: DHA inhibited it but EPA stimulated it. TNF-α blocked DHA-induced decrease in PPARγ phosphorylation, which eventually led to a decrease in adiponectin. Roscovitine blocked EPA-induced increase in PPARγ phosphorylation, but the corresponding increase in adiponectin was non-significant. DHA compared with EPA led to a greater increase in cellular and secreted adiponectin at relative low concentrations by increasing PPARγ expression and inhibiting its phosphorylation at Ser273. DHA may be more beneficial than EPA in reducing risks of NCDs.

Leptin and Adiponectin Modulate the Self-renewal of Normal Human Breast Epithelial Stem Cells.

PubMed

Esper, Raymond M; Dame, Michael; McClintock, Shannon; Holt, Peter R; Dannenberg, Andrew J; Wicha, Max S; Brenner, Dean E

2015-12-01

Multiple mechanisms are likely to account for the link between obesity and increased risk of postmenopausal breast cancer. Two adipokines, leptin and adiponectin, are of particular interest due to their opposing biologic functions and associations with breast cancer risk. In the current study, we investigated the effects of leptin and adiponectin on normal breast epithelial stem cells. Levels of leptin in human adipose explant-derived conditioned media positively correlated with the size of the normal breast stem cell pool. In contrast, an inverse relationship was found for adiponectin. Moreover, a strong linear relationship was observed between the leptin/adiponectin ratio in adipose conditioned media and breast stem cell self-renewal. Consistent with these findings, exogenous leptin stimulated whereas adiponectin suppressed breast stem cell self-renewal. In addition to local in-breast effects, circulating factors, including leptin and adiponectin, may contribute to the link between obesity and breast cancer. Increased levels of leptin and reduced amounts of adiponectin were found in serum from obese compared with age-matched lean postmenopausal women. Interestingly, serum from obese women increased stem cell self-renewal by 30% compared with only 7% for lean control serum. Taken together, these data suggest a plausible explanation for the obesity-driven increase in postmenopausal breast cancer risk. Leptin and adiponectin may function as both endocrine and paracrine/juxtacrine factors to modulate the size of the normal stem cell pool. Interventions that disrupt this axis and thereby normalize breast stem cell self-renewal could reduce the risk of breast cancer. ©2015 American Association for Cancer Research.

Adiponectin Enhances the Responsiveness of the Olfactory System

PubMed Central

Loch, Diana; Heidel, Christian; Breer, Heinz; Strotmann, Jörg

2013-01-01

The peptide hormone adiponectin is secreted by adipose tissue and the circulating concentration is reversely correlated with body fat mass; it is considered as starvation signal. The observation that mature sensory neurons of the main olfactory epithelium express the adiponectin receptor 1 has led to the concept that adiponectin may affect the responsiveness of the olfactory system. In fact, electroolfactogram recordings from olfactory epithelium incubated with exogenous adiponectin resulted in large amplitudes upon odor stimulation. To determine whether the responsiveness of the olfactory sensory neurons was enhanced, we have monitored the odorant-induced expression of the immediate early gene Egr1. It was found that in an olfactory epithelium incubated with nasally applied adiponectin the number of Egr1 positive cells was significantly higher compared to controls, suggesting that adiponectin rendered the olfactory neurons more responsive to an odorant stimulus. To analyze whether the augmented responsiveness of sensory neurons was strong enough to elicit a higher neuronal activity in the olfactory bulb, the number of activated periglomerular cells of a distinct glomerulus was determined by monitoring the stimulus-induced expression of c-fos. The studies were performed using the transgenic mOR256-17-IRES-tauGFP mice which allowed to visualize the corresponding glomerulus and to stimulate with a known ligand. The data indicate that upon exposure to 2,3-hexanedione in adiponectin-treated mice the number of activated periglomerular neurons was significantly increased compared to controls. The results of this study indicate that adiponectin increases the responsiveness of the olfactory system, probably due to a higher responsiveness of olfactory sensory neurons. PMID:24130737

Insulin-independent role of adiponectin receptor signaling in Drosophila germline stem cell maintenance.

PubMed

Laws, Kaitlin M; Sampson, Leesa L; Drummond-Barbosa, Daniela

2015-03-15

Adipocytes have key endocrine roles, mediated in large part by secreted protein hormones termed adipokines. The adipokine adiponectin is well known for its role in sensitizing peripheral tissues to insulin, and several lines of evidence suggest that adiponectin might also modulate stem cells/precursors. It remains unclear, however, how adiponectin signaling controls stem cells and whether this role is secondary to its insulin-sensitizing effects or distinct. Drosophila adipocytes also function as an endocrine organ and, although no obvious adiponectin homolog has been identified, Drosophila AdipoR encodes a well-conserved homolog of mammalian adiponectin receptors. Here, we generate a null AdipoR allele and use clonal analysis to demonstrate an intrinsic requirement for AdipoR in germline stem cell (GSC) maintenance in the Drosophila ovary. AdipoR null GSCs are not fully responsive to bone morphogenetic protein ligands from the niche and have a slight reduction in E-cadherin levels at the GSC-niche junction. Conversely, germline-specific overexpression of AdipoR inhibits natural GSC loss, suggesting that reduction in adiponectin signaling might contribute to the normal decline in GSC numbers observed over time in wild-type females. Surprisingly, AdipoR is not required for insulin sensitization of the germline, leading us to speculate that insulin sensitization is a more recently acquired function than stem cell regulation in the evolutionary history of adiponectin signaling. Our findings establish Drosophila female GSCs as a new system for future studies addressing the molecular mechanisms whereby adiponectin receptor signaling modulates stem cell fate. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of houttuynia cordata aetherolea on adiponectin and connective tissue growth factor in a rat model of diabetes mellitus.

PubMed

Wang, Hai-Ying; Bao, Jun-Lu

2012-03-01

To determine the effect of Houttuynia cordata Aetherolea on connective tissue growth factor and adiponectin in a rat model of diabetes mellitus (DM). DM was induced in rats using streptozotocin (STZ) and high glucose-lipid animal feed. Animals were then treated with Houttuynia cordata Aetherolea for 8 weeks. Changes in connective tissue growth factor and adiponectin levels in rats were observed. Connective tissue growth factor and adiponectin levels in rats with DM improved after Houttuynia cordata Aetherolea treatment. Houttuynia cordata Aetherolea had a positive effect on rats with DM by reducing levels of connective tissue growth factor and increasing adiponectin levels.

Exendin-4 Upregulates Adiponectin Level in Adipocytes via Sirt1/Foxo-1 Signaling Pathway

PubMed Central

Wang, Anping; Li, Ting; An, Ping; Yan, Wenhua; Zheng, Hua; Wang, Baoan; Mu, Yiming

2017-01-01

Glucagon-like peptide-1 (GLP-1) receptor plays an essential role in regulating glucose metabolism. GLP-1 receptor agonists have been widely used for treating diabetes and other insulin resistance-related diseases. However, mechanisms underlying the anti-diabetic effects of GLP-1 receptor agonists remain largely unknown. In this study, we investigated the effects of GLP-1 agonist exendin-4 on the expression of adiponectin, an insulin sensitizing hormone. We found that exendin-4 increased the expression and secretion of adiponectin both in vitro and in vivo. Our data showed that exendin-4 upregulated adiponectin expression at both mRNA and protein levels in adipocytes and adipose tissues. The effects of exendin-4 on adiponectin expression were dependent on the GLP-1 receptor. We further demonstrated important roles of Sirt1 and transcriptional factor Foxo-1 in mediating the function of exendin-4 in regulating adiponectin expression. Suppression of Sirt1 or Foxo-1 expression significantly impaired exendin-4-induced adiponectin expression. Consistently, exendin-4 up-regulated Sirt1 and Foxo-1 expression in vivo. Our work is the first study demonstrating the role of Sirt1/Foxo-1 in regulating the regulatory function of a GLP-1 receptor agonist in adiponectin expression both in vitro and in vivo. The results provide important information for the mechanism underlying the function of GLP-1R on improving insulin resistance and related diseases. PMID:28122026

Fisetin up-regulates the expression of adiponectin in 3T3-L1 adipocytes via the activation of silent mating type information regulation 2 homologue 1 (SIRT1)-deacetylase and peroxisome proliferator-activated receptors (PPARs).

PubMed

Jin, Taewon; Kim, Oh Yoen; Shin, Min-Jeong; Choi, Eun Young; Lee, Sung Sook; Han, Ye Sun; Chung, Ji Hyung

2014-10-29

Adiponectin, an adipokine, has been described as showing physiological benefits against obesity-related malfunctions and vascular dysfunction. Several natural compounds that promote the expression and secretion of adipokines in adipocytes could be useful for treating metabolic disorders. This study investigated the effect of fisetin, a dietary flavonoid, on the regulation of adiponectin in adipocytes using 3T3-L1 preadipocytes. The expression and secretion of adiponectin increased in 3T3-L1 cells upon treatment with fisetin in a dose-dependent manner. Fisetin-induced adiponectin secretion was inhibited by peroxisome proliferator-activated receptor (PPAR) antagonists. It was also revealed that fisetin increased the activities of PPARs and silent mating type information regulation 2 homologue 1 (SIRT1) in a dose-dependent manner. Furthermore, the up-regulation of adiponectin and the activation of PPARs induced by fisetin were prevented by a SIRT1 inhibitor. Fisetin also promoted deacetylation of PPAR γ coactivator 1 (PGC-1) and its interaction with PPARs. SIRT knockdown by siRNA significantly decreased both adiponectin production and PPARs-PGC-1 interaction. These results provide evidence that fisetin promotes the gene expression of adiponectin through the activation of SIRT1 and PPARs in adipocytes.

Adiponectin and the mediation of HDL-cholesterol change with improved lifestyle: the Look AHEAD Study[S

PubMed Central

Belalcazar, L. Maria; Lang, Wei; Haffner, Steven M.; Hoogeveen, Ron C.; Pi-Sunyer, F. Xavier; Schwenke, Dawn C.; Balasubramanyam, Ashok; Tracy, Russell P.; Kriska, Andrea P.; Ballantyne, Christie M.

2012-01-01

Adipose tissue dysfunction plays a key role in the development of the metabolic abnormalities characteristic of type 2 diabetes (T2DM) and participates actively in lipid metabolism. Adiponectin, found abundantly in circulation and a marker of adipose health, is decreased in obese persons with T2DM. We investigated whether the changes in adiponectin with an intensive lifestyle intervention (ILI) for weight loss could potentially mediate the increase in low HDL-cholesterol (HDL-C) with ILI. Adiponectin and its fractions were determined using an ELISA with selective protease treatment in 1,397 participants from Look AHEAD, a trial examining whether ILI will reduce cardiovascular events in overweight/obese subjects with T2DM when compared with a control arm, diabetes support and education (DSE). Multivariable regression and mediational analyses were performed for adiponectin and its high-molecular-weight (HMW) and non-HMW fractions. ILI increased baseline HDL-C by 9.7% and adiponectin by 11.9%; changes with DSE were 1.3% and 0.2%, respectively (P < 0.0001). In a model including changes in weight, fitness, triglycerides, and glucose control and that adjusted for demographics and medical history, adiponectin changes remained significantly associated with HDL-C change. Data supported the contribution of changes in both HMW- and non-HMW-adiponectin to the improvement in HDL-C with ILI PMID:22956782

Salivary pH as a marker of plasma adiponectin concentrations in Women.

PubMed

Tremblay, Monique; Loucif, Yacine; Methot, Julie; Brisson, Diane; Gaudet, Daniel

2012-02-03

Plasma adiponectin is a significant correlate of the pro-inflammatory cardiometabolic risk profile associated with obesity and type 2 diabetes. Salivary pH is influenced by several cardiometabolic risk components such as inflammation, oxidation and numerous oral and systemic health modulators, including the menopausal status. This study aimed to assess the association between plasma adiponectin concentrations and salivary pH in women according to the menopausal status. Unstimulated saliva collection was performed in 151 Caucasian women of French-Canadian origin (53 premenopausal women (PMW) and 98 menopausal women (MW)). Student's t test, ANOVA and linear regression models were used to assess the association between plasma adiponectin concentrations and salivary pH. Plasma adiponectin levels increased as a function of salivary pH in the whole sample and among MW (r = 0.29 and r = 0.36, p < 0.001). The proportion of the variance of plasma adiponectin levels explained by the salivary pH (R2) was 10.8% (p < 0.001). Plasma adiponectin levels progressively increased across salivary pH quartiles (p = 0.005). These results suggest that salivary pH is a significant correlate of plasma adiponectin levels in women. With the increasing prevalence of type 2 diabetes and obesity, new technologies should be developed to more easily monitor health status, disease onset and progression. Salivary pH, a simple, inexpensive and non-invasive measure, could be a very promising avenue.

Undercarboxylated osteocalcin is associated with insulin resistance, but not adiponectin, during pregnancy.

PubMed

Srichomkwun, Panudda; Houngngam, Natnicha; Pasatrat, Sophitsachi; Tharavanij, Thipaporn; Wattanachanya, Lalita; Khovidhunkit, Weerapan

2016-07-01

In mice, undercarboxylated osteocalcin (ucOC) improves beta-cell function and insulin sensitivity through adiponectin. In humans, levels of total osteocalcin (OC) and ucOC were negatively correlated with insulin resistance (IR) indices in patients with type 2 diabetes. Whether ucOC plays a role in glucose homeostasis and whether its effect is mediated through adiponectin during pregnancy is unclear. Serum levels of total OC, ucOC, and adiponectin were measured in 130 pregnant women with varying degrees of IR [gestational diabetes mellitus (GDM), n = 74 and non-GDM, n = 56]. In all participants, total OC and ucOC levels were positively correlated with HOMA-IR and HOMA-%B, and negatively correlated with QUICKI. In contrast, adiponectin levels were negatively correlated with HOMA-IR and positively correlated with QUICKI (P < 0.01, both). However, neither total OC nor ucOC was associated with adiponectin. Although none of these markers could help distinguish women with and without GDM, total OC and ucOC levels were significantly higher in non-GDM women who had 1 abnormal OGTT value than those who had all normal OGTT values. Total OC and ucOC levels were significantly correlated with insulin secretion and IR indices, but not adiponectin levels, in pregnant women. Changes in OC might be a sensitive response to increased IR during pregnancy, which was not mediated through adiponectin.

Adiponectin and markers of metabolic syndrome in obese children and adolescents: impact of 8-mo regular physical exercise program.

PubMed

Nascimento, Henrique; Costa, Elísio; Rocha, Susana; Lucena, Clarice; Rocha-Pereira, Petronila; Rêgo, Carla; Mansilha, Helena Ferreira; Quintanilha, Alexandre; Aires, Luísa; Mota, Jorge; Santos-Silva, Alice; Belo, Luís

2014-08-01

Adiponectin circulates as low-, medium-, and high-molecular-weight multimers (LMW, MMW, and HMW) and influences lipid profile and insulin resistance (IR), HMW being considered as the most biologically active form. We aimed to study the relation between adiponectin and markers of metabolic syndrome (MS) in pediatric obesity, and the impact of physical exercise. The study consisted of a cross-sectional part and an 8-mo physical exercise program. Lipid profile, insulin, glucose, C-reactive protein (CRP), total adiponectin (TA), and homeostasis model assessment IR (HOMA-IR) were measured. Adiponectin multimers were studied in a prepubertal group. Obesity is associated with increased dyslipidemia, IR, and inflammation. TA is correlated inversely with adiposity, triglycerides, HOMA-IR, and CRP, and positively with high-density lipoprotein cholesterol (HDLc)/total cholesterol (TC) ratio. HMW mimicked TA associations. The intervention program led to a reduction of TC, low-density lipoprotein cholesterol (LDLc), insulin, HOMA-IR, and trunk percentage of fat, and an increase of HDLc/TC ratio, in the obese group. BMI improvements prevented adiponectin reduction and correlated with increments in HMW and MMW. Obesity-related increase in MS features might be linked to lower adiponectin. HMW and MMW were the multimers that most explained the MS features. The intervention program improved the lipid profile and IR, and prevented the reduction of adiponectin.

Nicotinic acid increases adiponectin secretion from differentiated bovine preadipocytes through G-protein coupled receptor signaling.

PubMed

Kopp, Christina; Hosseini, Afshin; Singh, Shiva P; Regenhard, Petra; Khalilvandi-Behroozyar, Hamed; Sauerwein, Helga; Mielenz, Manfred

2014-11-18

The transition period in dairy cows (3 weeks prepartum until 3 weeks postpartum) is associated with substantial mobilization of energy stores, which is often associated with metabolic diseases. Nicotinic acid (NA) is an antilipolytic and lipid-lowering compound used to treat dyslipidaemia in humans, and it also reduces non-esterified fatty acids in cattle. In mice the G-protein coupled receptor 109A (GPR109A) ligand NA positively affects the secretion of adiponectin, an important modulator of glucose and fat metabolism. In cattle, the corresponding data linking NA to adiponectin are missing. Our objective was to examine the effects of NA on adiponectin and AMPK protein abundance and the expression of mRNAs of related genes such as chemerin, an adipokine that enhances adiponectin secretion in vitro. Differentiated bovine adipocytes were incubated with pertussis toxin (PTX) to verify the involvement of GPR signaling, and treated with 10 or 15 µM NA for 12 or 24 h. NA increased adiponectin concentrations (p ≤ 0.001) and the mRNA abundances of GPR109A (p ≤ 0.05) and chemerin (p ≤ 0.01). Pre-incubation with PTX reduced the adiponectin response to NA (p ≤ 0.001). The NA-stimulated secretion of adiponectin and the mRNA expression of chemerin in the bovine adipocytes were suggestive of GPR signaling-dependent improved insulin sensitivity and/or adipocyte metabolism in dairy cows.

Adiponectin and the mediation of HDL-cholesterol change with improved lifestyle: the Look AHEAD Study.

PubMed

Belalcazar, L Maria; Lang, Wei; Haffner, Steven M; Hoogeveen, Ron C; Pi-Sunyer, F Xavier; Schwenke, Dawn C; Balasubramanyam, Ashok; Tracy, Russell P; Kriska, Andrea P; Ballantyne, Christie M

2012-12-01

Adipose tissue dysfunction plays a key role in the development of the metabolic abnormalities characteristic of type 2 diabetes (T2DM) and participates actively in lipid metabolism. Adiponectin, found abundantly in circulation and a marker of adipose health, is decreased in obese persons with T2DM. We investigated whether the changes in adiponectin with an intensive lifestyle intervention (ILI) for weight loss could potentially mediate the increase in low HDL-cholesterol (HDL-C) with ILI. Adiponectin and its fractions were determined using an ELISA with selective protease treatment in 1,397 participants from Look AHEAD, a trial examining whether ILI will reduce cardiovascular events in overweight/obese subjects with T2DM when compared with a control arm, diabetes support and education (DSE). Multivariable regression and mediational analyses were performed for adiponectin and its high-molecular-weight (HMW) and non-HMW fractions. ILI increased baseline HDL-C by 9.7% and adiponectin by 11.9%; changes with DSE were 1.3% and 0.2%, respectively (P < 0.0001). In a model including changes in weight, fitness, triglycerides, and glucose control and that adjusted for demographics and medical history, adiponectin changes remained significantly associated with HDL-C change. Data supported the contribution of changes in both HMW- and non-HMW-adiponectin to the improvement in HDL-C with ILI.

The relationship between metabolic status and levels of adiponectin and ghrelin in lean women with polycystic ovary syndrome.

PubMed

Bik, Wojciech; Baranowska-Bik, Agnieszka; Wolinska-Witort, Ewa; Chmielowska, Magdalena; Martynska, Lidia; Baranowska, Boguslawa

2007-06-01

Polycystic ovary syndrome (PCOS) is commonly associated with insulin resistance, obesity, dyslipidemia and hypertension. Adiponectin, an adipocyte-specific protein with important roles in glucose and lipid homeostasis, possesses antidiabetic and insulin-sensitizing properties. Ghrelin, a protein ligand for the growth hormone secretagog receptor, has been shown to stimulate food intake and to influence energy balance, insulin signaling and glucose metabolism. We aimed to evaluate the relationships between metabolic alterations and adiponectin and ghrelin levels in lean PCOS women, compared with lean and obese women. The study was carried out on 20 non-obese PCOS women aged 20 - 48 years and age-matched groups of 45 healthy lean and 37 obese women. Hormonal and biochemical parameters, adiponectin and ghrelin concentrations and anthropometric data were determined. In PCOS subjects, we found increased homeostasis model assessment - insulin resistance index (HOMA-IR) with non-significant differences in adiponectin and ghrelin concentrations compared with healthy women, although the PCOS group showed a tendency to lower adiponectin levels. However, ghrelin levels in PCOS women were significantly higher than in obese women. Moreover, we observed a negative correlation between adiponectin and testosterone, cholesterol, triglycerides, glucose and diastolic blood pressure in PCOS. In conclusion, it can be suggested that higher values of HOMA-IR with lower adiponectin levels may indicate future development of metabolic syndrome or other metabolic disturbances in lean PCOS women.

Association between the level of circulating adiponectin and prediabetes: A meta-analysis

PubMed Central

Lai, Huasheng; Lin, Nie; Xing, Zhenzhen; Weng, Huanhuan; Zhang, Hua

2015-01-01

Aims/Introduction Adiponectin has been proposed to have an essential role in the regulation of insulin sensitivity and metabolism, but previous studies on levels of adiponectin in prediabetes remain inconsistent. The present study aimed to assess the differences of adiponectin levels between prediabetes patients and healthy controls by carrying out a meta-analysis. Materials and Methods We carried out a systematic literature search of PubMed, EMBASE, and other databases for case–control studies and cohort studies measuring adiponectin levels in serum or plasma from prediabetes patients and healthy controls. The pooled weighted mean difference (WMD) and 95% confidence interval (CI) were used to estimate the association between adiponectin levels and prediabetes. Results Three cohort studies and 15 case–control studies with a total of 41,841 participants were included in the meta-analysis. The results showed that circulating adiponectin levels in prediabetes patients were significantly lower than that of healthy controls (WMD –1.694 μg/mL; 95% CI –2.151, –1.237; P < 0.001). Subgroup analysis showed more significant differences between prediabetes patients and healthy controls when the ratio of the homeostatic model assessment of insulin resistance was >2.12 (WMD −2.95 μg/mL; 95% CI –4.103, –1.806; P < 0.001) and average age was >60 years (WMD −2.20 μg/mL; 95% CI –3.207, –1.201; P < 0.001). Additionally, WMD in adiponectin showed a trend of direct correlation in subgroups of homeostatic model assessment of insulin resistance ratio, body mass index and age. Conclusions The present meta-analysis supports adiponectin levels in prediabetes patients being lower than that of healthy controls,indicating that the level of circulating adiponectin decreases before the onset of diabetes. PMID:26221520

Adiponectin and Lipid Profiles Compared with Insulins in Relation to Early Growth of British South Asian and European Children: The Manchester Children's Growth and Vascular Health Study

PubMed Central

Bansal, Narinder; Anderson, Simon G.; Vyas, Avni; Gemmell, Isla; Charlton-Menys, Valentine; Oldroyd, John; Pemberton, Philip; Durrington, Paul N.; Clayton, Peter E.

2011-01-01

Context: Adiponectin, high-density lipoprotein cholesterol (HDL-C) and insulin concentrations may be important in the pathophysiology of cardiovascular disease. Objective: We tested the hypothesis that serum adiponectin rather than insulin differs from early life, between South Asians and Europeans, with a potentially key role in excess cardiovascular risk characteristic of adult South Asians. Design and Participants: We conducted a longitudinal study of 215 British-born children of European (n = 138) and South Asian (n = 77) origin, from birth to 3 yr. Main Outcome Measure: Serum adiponectin, insulin, proinsulin and HDL-C concentrations were assessed in relation to ethnic group and growth in anthropometric variables from 0–3 yr of age. Results: Serum adiponectin was lower in South Asian children, despite their smaller size, notable at age 3–6 months (9.5 vs. 11.8 mg/liter; P = 0.04), with no ethnic differences in serum lipids or insulin or proinsulin. In mixed-effects longitudinal models for HDL-C, determinants were adiponectin (P = 0.034), age (P < 0.001), and body mass index (P < 0.001) but not ethnicity. None of these or growth variables affected either insulin or proinsulin. In a fully adjusted mixed-effects longitudinal model including age, sex, insulin, and proinsulin, the independent determinants of serum adiponectin were height [21.3 (95% confidence interval = 31.7–10.8 cm lower, for every 1 mmol/liter increase in adiponectin, P < 0.001], HDL-C [2.8 (1.3–4.2) mmol/liter higher, P < 0.0001], body mass index (lower, P = 0.03), and South Asian ethnicity (lower, P = 0.01). Conclusions: These British South Asian-origin infants have lower serum adiponectin but no differences in HDL-C or insulin molecules. In South Asians, factors affecting adiponectin metabolism in early life, rather than insulin resistance, likely determine later excess cardiovascular risk. PMID:21632814

Improvement in insulin sensitivity by weight loss does not affect hyperinsulinemia-mediated reduction in total and high molecular weight adiponectin: a MONET study.

PubMed

Drapeau, Sophie; Doucet, Eric; Rabasa-Lhoret, Remi; Brochu, Martin; Prud'homme, Denis; Imbeault, Pascal

2011-04-01

Acute hyperinsulinemia reduces total and high molecular weight (HMW) adiponectin levels in humans. Whether an increase in insulin sensitivity (IS) is accompanied by a greater suppressive effect of hyperinsulinemia on adiponectin levels is unknown, however. To clarify the inhibitory role of insulin on adiponectin, total and HMW adiponectin levels were measured during acute hyperinsulinemia before and after an improvement in insulin sensitivity in response to weight loss. Forty-six overweight and obese postmenopausal women were randomized to either 6-month caloric restriction (CR) alone (n = 22), or CR with resistance training (CR+RT, n = 24). IS (hyperinsulinemic-euglycemic clamp) was assessed before and after weight loss. Total and HMW adiponectin levels were measured by ELISA at baseline, 90, 160, and 180 min of each clamp. Relative mean body weight loss was -8.0% ± 4.4% for both groups (CR: -7.7% ± 3.8%; CR+RT: -8.2% ± 5.0%). IS increased significantly, by 18.4% ± 25.3% (CR: 19.3% ± 29.7%; CR+RT: 17.7% ± 21.0%). Before each intervention, total and HMW adiponectin levels in both groups significantly decreased in response to hyperinsulinemia (total: -8.4% ± 19.4%; HMW: -3.2% ± 13.2%). Despite the improvement in IS seen after each intervention, a similar pattern of reduction to that before weight loss was observed in total and HMW adiponectin levels during hyperinsulinemia. These results establish that total and HMW adiponectin levels decline during a hyperinsulinemic-euglycemic clamp. Also, the insulin-sensitizing effect of weight loss via caloric restriction alone or with resistance training does not amplify the reduction in adiponectin levels observed during hyperinsulinemia in healthy postmenopausal women.

Leptin-adiponectin imbalance as a marker of metabolic syndrome among Chinese children and adolescents: The BCAMS study.

PubMed

Li, Ge; Xu, Linxin; Zhao, Yanglu; Li, Lujiao; Fu, Junling; Zhang, Qian; Li, Naishi; Xiao, Xinhua; Li, Changhong; Mi, Jie; Gao, Shan; Li, Ming

2017-01-01

Leptin and adiponectin have opposite effects on subclinical inflammation and insulin resistance, both involved in the development of metabolic syndrome (MS). We aimed to investigate whether leptin/adiponectin ratio (L/A), as a marker of these two adipokines imbalance, may improve diagnosis of MS in children and adolescents, and determined its cut-off value in the diagnosis of MS. A total of 3,428 subjects aged 6-18 years were selected from Beijing Child and Adolescent Metabolic Syndrome study. Adipokine leptin and adiponectin were measured using enzyme-linked immunosorbent assay. Odds ratio of MS per 1 z-score of adipokine was examined using logistic regression. Diagnosis accuracy was assessed using c-statistics (AUC) and net reclassification index. The levels of leptin and L/A increased with number of positive MS components, while the levels of adiponectin declined in both boys and girls (all P <0.001). AUCs for diagnosis of MS in girls were 0.793, 0.773, and 0.689 using L/A, leptin and adiponectin, respectively; and AUCs in boys were 0.822, 0.798, and 0.697 for L/A, leptin and adiponectin, respectively. Notably, L/A outperformed individual leptin or adiponectin in discriminating a diagnosis of MS (all P < 0.02 in AUC comparisons). In addition, the optimal cut-offs of L/A by ROC curve differed by genders and pubertal stages, which were 1.63, 1.28, 1.95 and 1.53 ng/ug for total, pre-, mid- and postpubertal boys, respectively and 2.19, 0.87,1.48 and 2.27 ng/ug for total, pre-, mid- and postpubertal girls, respectively, yielding high sensitivity and moderate specificity for a screening test. In this pediatric population, leptin-adiponectin imbalance, as reflected by an increase in L/A level, was found to be a better diagnostic biomarker for MS than leptin or adiponectin alone. Future longitudinal studies are needed to further validate the gender-specific cutoff values.

Adiponectin selectively inhibits oxytocin neurons of the paraventricular nucleus of the hypothalamus

PubMed Central

Hoyda, Ted D; Fry, Mark; Ahima, Rexford S; Ferguson, Alastair V

2007-01-01

Adiponectin is an adipocyte derived hormone which acts in the brain to modulate energy homeostasis and autonomic function. The paraventricular nucleus of the hypothalamus (PVN) which plays a key role in controlling pituitary hormone secretion has been suggested to be a central target for adiponectin actions. A number of hormones produced by PVN neurons have been implicated in the regulation of energy homeostasis including oxytocin, corticotropin releasing hormone and thyrotropin releasing hormone. In the present study we investigated the role of adiponectin in controlling the excitability of magnocellular (MNC – oxytocin or vasopressin secreting) neurons within the PVN. Using RT-PCR techniques we have shown expression of both adiponectin receptors in the PVN. Patch clamp recordings from MNC neurons in hypothalamic slices have also identified mixed (27% hyperpolarization, 42% depolarization) effects of adiponectin in modulating the excitability of the majority of MNC neurons tested. These effects are maintained when cells are placed in synaptic isolation using tetrodotoxin. Additionally we combined electrophysiological recordings with single cell RT-PCR to examine the actions of adiponectin on MNC neurons which expressed oxytocin only, vasopressin only, or both oxytocin and vasopressin mRNA and assess the profile of receptor expression in these subgroups. Adiponectin was found to hyperpolarize 100% of oxytocin neurons tested (n = 6), while vasopressin cells, while all affected (n = 6), showed mixed responses. Further analysis indicates oxytocin neurons express both receptors (6/7) while vasopressin neurons express either both receptors (3/8) or one receptor (5/8). In contrast 6/6 oxytocin/vasopressin neurons were unaffected by adiponectin. Co-expressing oxytocin and vasopressin neurons express neither receptor (4/6). The results presented in this study suggest that adiponectin plays specific roles in controlling the excitability oxytocin secreting neurons, actions which correlate with the current literature showing increased oxytocin secretion in the obese population. PMID:17947308

Reduced adiponectin expression after high-fat diet is associated with selective up-regulation of ALDH1A1 and further retinoic acid receptor signaling in adipose tissue

PubMed Central

Landrier, Jean-Francois; Kasiri, Elnaz; Karkeni, Esma; Mihály, Johanna; Béke, Gabriella; Weiss, Kathrin; Lucas, Renata; Aydemir, Gamze; Salles, Jérome; Walrand, Stéphane; de Lera, Angel R.; Rühl, Ralph

2017-01-01

Adiponectin is an adipocyte-derived adipokine with potent antidiabetic, anti-inflammatory, and antiatherogenic activity. Long-term, high-fat diet results in gain of body weight, adiposity, further inflammatory-based cardiovascular diseases, and reduced adiponectin secretion. Vitamin A derivatives/retinoids are involved in several of these processes, which mainly take place in white adipose tissue (WAT). In this study, we examined adiponectin expression as a function of dietary high-fat and high–vitamin A conditions in mice. A decrease of adiponectin expression in addition to an up-regulation of aldehyde dehydrogenase A1 (ALDH1A1), retinoid signaling, and retinoic acid response element signaling was selectively observed in WAT of mice fed a normal–vitamin A, high-fat diet. Reduced adiponectin expression in WAT was also observed in mice fed a high–vitamin A diet. Adipocyte cell culture revealed that endogenous and synthetic retinoic acid receptor (RAR)α- and RARγ-selective agonists, as well as a synthetic retinoid X receptor agonist, efficiently reduced adiponectin expression, whereas ALDH1A1 expression only increased with RAR agonists. We conclude that reduced adiponectin expression under high-fat dietary conditions is dependent on 1) increased ALDH1A1 expression in adipocytes, which does not increase all-trans-retinoic acid levels; 2) further RAR ligand–induced, WAT-selective, increased retinoic acid response element–mediated signaling; and 3) RAR ligand–dependent reduction of adiponectin expression.—Landrier, J.-F., Kasiri, E., Karkeni, E., Mihály, J., Béke, G., Weiss, K., Lucas, R., Aydemir, G., Salles, J., Walrand, S., de Lera, A. R., Rühl, R. Reduced adiponectin expression after high-fat diet is associated with selective up-regulation of ALDH1A1 and further retinoic acid receptor signaling in adipose tissue. PMID:27729412

Adiponectin and resistin in acute and chronic graft-vs-host disease patients undergoing allogeneic hematopoietic stem cell transplantation.

PubMed

Robak, Oliver; Kuzmina, Zoya; Winkler, Andreas; Kalhs, Peter; Rabitsch, Werner; Greinix, Hildegard

2016-06-30

To investigate the association of adiponectin and resistin levels in patients undergoing hematopoietic stem cell transplantation (HSCT) with the clinical outcome, including the occurrence of acute and chronic graft-vs-host disease (GVHD), non-relapse mortality, and overall survival. We prospectively collected serum samples from 40 patients undergoing either autologous (n=12; 10 male) or allogeneic (n=28; 11 male) HSCT for up to 12 months post HSCT and determined adiponectin and resistin serum concentrations using enzyme-linked immunosorbent assay. There were no significant differences in adiponectin levels (18.5 vs 9.3 μg/mL, P=0.071) and adiponectin/BMI ratio (0.82 vs 0.39, P=0.068) between patients with acute GVHD grades 2-4 and autologous controls. However, resistin values were significantly lower in patients with acute GVHD grades 2-4 than in autologous controls (4.6 vs 7.3 ng/mL, P=0.030). Adiponectin levels were higher in patients with chronic GVHD (n=17) than in autologous controls (13.5 vs 7.6 μg/mL, P=0.051), but the difference was not significant. Adiponectin/BMI ratio was significantly higher in patients with chronic GVHD than in autologous controls (0.59 vs 0.25, P=0.006). Patients dying from relapse also had significantly lower adiponectin levels (8.2 μg/mL) and adiponectin/BMI ratio (0.3) on admission than surviving allogeneic (15.8 µg/mL, P=0.030 and 0.7, P=0.004) and surviving autologous patients (19.2 μg/mL, P=0.031 and 0.7, P=0.021). Adiponectin and resistin levels were altered in patients with acute and chronic GVHD compared to autologous controls and were associated with overall survival and relapse mortality in patients undergoing allogeneic HSCT.

Adiponectin and resistin in acute and chronic graft-vs-host disease patients undergoing allogeneic hematopoietic stem cell transplantation

PubMed Central

Robak, Oliver; Kuzmina, Zoya; Winkler, Andreas; Kalhs, Peter; Rabitsch, Werner; Greinix, Hildegard

2016-01-01

Aim To investigate the association of adiponectin and resistin levels in patients undergoing hematopoietic stem cell transplantation (HSCT) with the clinical outcome, including the occurrence of acute and chronic graft-vs-host disease (GVHD), non-relapse mortality, and overall survival. Methods We prospectively collected serum samples from 40 patients undergoing either autologous (n = 12; 10 male) or allogeneic (n = 28; 11 male) HSCT for up to 12 months post HSCT and determined adiponectin and resistin serum concentrations using enzyme-linked immunosorbent assay. Results There were no significant differences in adiponectin levels (18.5 vs 9.3 µg/mL, P = 0.071) and adiponectin/BMI ratio (0.82 vs 0.39, P = 0.068) between patients with acute GVHD grades 2-4 and autologous controls. However, resistin values were significantly lower in patients with acute GVHD grades 2-4 than in autologous controls (4.6 vs 7.3 ng/mL, P = 0.030). Adiponectin levels were higher in patients with chronic GVHD (n = 17) than in autologous controls (13.5 vs 7.6 µg/mL, P = 0.051), but the difference was not significant. Adiponectin/BMI ratio was significantly higher in patients with chronic GVHD than in autologous controls (0.59 vs 0.25, P = 0.006). Patients dying from relapse also had significantly lower adiponectin levels (8.2 µg/mL) and adiponectin/BMI ratio (0.3) on admission than surviving allogeneic (15.8 µg/mL, P = 0.030 and 0.7, P = 0.004) and surviving autologous patients (19.2 µg/mL, P = 0.031 and 0.7, P = 0.021). Conclusion Adiponectin and resistin levels were altered in patients with acute and chronic GVHD compared to autologous controls and were associated with overall survival and relapse mortality in patients undergoing allogeneic HSCT. PMID:27374827

Adiponectin and lipid profiles compared with insulins in relation to early growth of British South Asian and European children: the Manchester children's growth and vascular health study.

PubMed

Bansal, Narinder; Anderson, Simon G; Vyas, Avni; Gemmell, Isla; Charlton-Menys, Valentine; Oldroyd, John; Pemberton, Philip; Durrington, Paul N; Clayton, Peter E; Cruickshank, J Kennedy

2011-08-01

Adiponectin, high-density lipoprotein cholesterol (HDL-C) and insulin concentrations may be important in the pathophysiology of cardiovascular disease. We tested the hypothesis that serum adiponectin rather than insulin differs from early life, between South Asians and Europeans, with a potentially key role in excess cardiovascular risk characteristic of adult South Asians. We conducted a longitudinal study of 215 British-born children of European (n = 138) and South Asian (n = 77) origin, from birth to 3 yr. Serum adiponectin, insulin, proinsulin and HDL-C concentrations were assessed in relation to ethnic group and growth in anthropometric variables from 0-3 yr of age. Serum adiponectin was lower in South Asian children, despite their smaller size, notable at age 3-6 months (9.5 vs. 11.8 mg/liter; P = 0.04), with no ethnic differences in serum lipids or insulin or proinsulin. In mixed-effects longitudinal models for HDL-C, determinants were adiponectin (P = 0.034), age (P < 0.001), and body mass index (P < 0.001) but not ethnicity. None of these or growth variables affected either insulin or proinsulin. In a fully adjusted mixed-effects longitudinal model including age, sex, insulin, and proinsulin, the independent determinants of serum adiponectin were height [21.3 (95% confidence interval = 31.7-10.8 cm lower, for every 1 mmol/liter increase in adiponectin, P < 0.001], HDL-C [2.8 (1.3-4.2) mmol/liter higher, P < 0.0001], body mass index (lower, P = 0.03), and South Asian ethnicity (lower, P = 0.01). These British South Asian-origin infants have lower serum adiponectin but no differences in HDL-C or insulin molecules. In South Asians, factors affecting adiponectin metabolism in early life, rather than insulin resistance, likely determine later excess cardiovascular risk.

Associations of adiponectin with individual European ancestry in African Americans: the Jackson Heart Study

PubMed Central

Bidulescu, Aurelian; Choudhry, Shweta; Musani, Solomon K.; Buxbaum, Sarah G.; Liu, Jiankang; Rotimi, Charles N.; Wilson, James G.; Taylor, Herman A.; Gibbons, Gary H.

2014-01-01

Background: Compared with European Americans, African Americans (AAs) exhibit lower levels of the cardio-metabolically protective adiponectin even after accounting for adiposity measures. Because few studies have examined in AA the association between adiponectin and genetic admixture, a dense panel of ancestry informative markers (AIMs) was used to estimate the individual proportions of European ancestry (PEA) for the AAs enrolled in a large community-based cohort, the Jackson Heart Study (JHS). We tested the hypothesis that plasma adiponectin and PEA are directly associated and assessed the interaction with a series of cardio-metabolic risk factors. Methods: Plasma specimens from 1439 JHS participants were analyzed by ELISA for adiponectin levels. Using pseudo-ancestral population genotype data from the HapMap Consortium, PEA was estimated with a panel of up to 1447 genome-wide preselected AIMs by a maximum likelihood approach. Interaction assessment, stepwise linear and cubic multivariable-adjusted regression models were used to analyze the cross-sectional association between adiponectin and PEA. Results: Among the study participants (62% women; mean age 48 ± 12 years), the median (interquartile range) of PEA was 15.8 (9.3)%. Body mass index (BMI) (p = 0.04) and insulin resistance (p = 0.0001) modified the association between adiponectin and PEA. Adiponectin was directly and linearly associated with PEA (β = 0.62 ± 0.28, p = 0.03) among non-obese (n = 673) and insulin sensitive participants (n = 1141; β = 0.74 ± 0.23, p = 0.001), but not among those obese or with insulin resistance. No threshold point effect was detected for non-obese participants. Conclusions: In a large AA population, the individual proportion of European ancestry was linearly and directly associated with plasma adiponectin among non-obese and non insulin-resistant participants, pointing to the interaction of genetic and metabolic factors influencing adiponectin levels. PMID:24575123

Genetic variants of adiponectin receptor 2 are associated with increased adiponectin levels and decreased triglyceride/VLDL levels in patients with metabolic syndrome.

PubMed

Broedl, Uli C; Lehrke, Michael; Fleischer-Brielmaier, Elisabeth; Tietz, Anne B; Nagel, Jutta M; Göke, Burkhard; Lohse, Peter; Parhofer, Klaus G

2006-05-15

Adiponectin acts as an antidiabetic, antiinflammatory and antiatherogenic adipokine. These effects are assumed to be mediated by the recently discovered adiponectin receptors AdipoR1 and AdipoR2. The purpose of this study was to determine whether variations in the AdipoR1 and AdipoR2 genes may contribute to insulin resistance, dyslipidemia and inflammation. We sequenced all seven coding exons of both genes in 20 unrelated German subjects with metabolic syndrome and tested genetic variants for association with glucose, lipid and inflammatory parameters. We identified three AdipoR2 variants (+795G/A, +870C/A and +963C/T) in perfect linkage disequilibrium (r2 = 1) with a minor allele frequency of 0.125. This haplotype was associated with higher plasma adiponectin levels and decreased fasting triglyceride, VLDL-triglyceride and VLDL-cholesterol levels. No association, however, was observed between the AdipoR2 SNP cluster and glucose metabolism. To our knowledge, this is the first study to identify an association between genetic variants of the adiponectin receptor genes and plasma adiponectin levels. Furthermore, our data suggest that AdipoR2 may play an important role in triglyceride/VLDL metabolism.

Adiponectin Deficiency Impairs Maternal Metabolic Adaptation to Pregnancy in Mice.

PubMed

Qiao, Liping; Wattez, Jean-Sebastien; Lee, Samuel; Nguyen, Amanda; Schaack, Jerome; Hay, William W; Shao, Jianhua

2017-05-01

Hypoadiponectinemia has been widely observed in patients with gestational diabetes mellitus (GDM). To investigate the causal role of hypoadiponectinemia in GDM, adiponectin gene knockout ( Adipoq -/- ) and wild-type (WT) mice were crossed to produce pregnant mouse models with or without adiponectin deficiency. Adenoviral vector-mediated in vivo transduction was used to reconstitute adiponectin during late pregnancy. Results showed that Adipoq -/- dams developed glucose intolerance and hyperlipidemia in late pregnancy. Increased fetal body weight was detected in Adipoq -/- dams. Adiponectin reconstitution abolished these metabolic defects in Adipoq -/- dams. Hepatic glucose and triglyceride production rates of Adipoq -/- dams were significantly higher than those of WT dams. Robustly enhanced lipolysis was found in gonadal fat of Adipoq -/- dams. Interestingly, similar levels of insulin-induced glucose disposal and insulin signaling in metabolically active tissues in Adipoq -/- and WT dams indicated that maternal adiponectin deficiency does not reduce insulin sensitivity. However, remarkably decreased serum insulin concentrations were observed in Adipoq -/- dams. Furthermore, β-cell mass, but not glucose-stimulated insulin release, in Adipoq -/- dams was significantly reduced compared with WT dams. Together, these results demonstrate that adiponectin plays an important role in controlling maternal metabolic adaptation to pregnancy. © 2017 by the American Diabetes Association.

Adiponectin Deficiency Impairs Maternal Metabolic Adaptation to Pregnancy in Mice

PubMed Central

Qiao, Liping; Wattez, Jean-Sebastien; Lee, Samuel; Nguyen, Amanda; Schaack, Jerome; Hay, William W.

2017-01-01

Hypoadiponectinemia has been widely observed in patients with gestational diabetes mellitus (GDM). To investigate the causal role of hypoadiponectinemia in GDM, adiponectin gene knockout (Adipoq−/−) and wild-type (WT) mice were crossed to produce pregnant mouse models with or without adiponectin deficiency. Adenoviral vector–mediated in vivo transduction was used to reconstitute adiponectin during late pregnancy. Results showed that Adipoq−/− dams developed glucose intolerance and hyperlipidemia in late pregnancy. Increased fetal body weight was detected in Adipoq−/− dams. Adiponectin reconstitution abolished these metabolic defects in Adipoq−/− dams. Hepatic glucose and triglyceride production rates of Adipoq−/− dams were significantly higher than those of WT dams. Robustly enhanced lipolysis was found in gonadal fat of Adipoq−/− dams. Interestingly, similar levels of insulin-induced glucose disposal and insulin signaling in metabolically active tissues in Adipoq−/− and WT dams indicated that maternal adiponectin deficiency does not reduce insulin sensitivity. However, remarkably decreased serum insulin concentrations were observed in Adipoq−/− dams. Furthermore, β-cell mass, but not glucose-stimulated insulin release, in Adipoq−/− dams was significantly reduced compared with WT dams. Together, these results demonstrate that adiponectin plays an important role in controlling maternal metabolic adaptation to pregnancy. PMID:28073830

Coffee consumption is associated with higher plasma adiponectin concentrations in women with or without type 2 diabetes: a prospective cohort study

PubMed Central

Williams, Catherine J.; Fargnoli, Jessica L.; Hwang, Janice J.; van Dam, Rob M.; Blackburn, George L.; Hu, Frank B.; Mantzoros, Christos S.

2009-01-01

To test whether the beneficial effects of coffee consumption in metabolism might be explained by changes in circulating levels of adiponectin, we evaluated self-reported habitual coffee and tea consumption and caffeine intake as predictors of plasma adiponectin concentrations among 982 diabetic and 1058 non-diabetic women without cardiovascular disease from the Nurses' Health Study. Women with and without diabetes who drank ≥4 cups of coffee per day had significantly higher adiponectin concentrations than those who didn't drink coffee regularly (7.7 vs. 6.1 μg/ml, respectively, in diabetic women, P=0.004; 15.0 vs. 13.2 μg/ml in nondiabetic women, P=0.04). Similar associations were observed for caffeine intake. We confirm previously reported inverse associations of coffee consumption with inflammatory markers, C-reactive protein and tumor necrosis factor-α receptor II. Adjustment for adiponectin did not weaken these associations, nor did adjustment for inflammatory markers attenuate the association between coffee consumption and adiponectin. High consumption of caffeine-containing coffee is associated with higher adiponectin and lower inflammatory marker concentrations. PMID:18070989

Adiponectin and leptin in overweight/obese and lean women with polycystic ovary syndrome.

PubMed

Chen, Chin-I; Hsu, Ming-I; Lin, Shyh-Hsiang; Chang, Yuan-Chin I; Hsu, Chun-Sen; Tzeng, Chii-Ruey

2015-04-01

The objective of this study was to evaluate the adiponectin and leptin levels in overweight/obese and lean women with polycystic ovary syndrome (PCOS). This was a retrospective study. Of the 422 studied patients, 224 women with PCOS and 198 women without PCOS were evaluated. Insulin resistance and the metabolic components were assessed. The adiponectin and leptin levels were also evaluated. Adiponectin was negatively correlated with insulin resistance, body mass index (BMI), and total testosterone, triglyceride, and low-density lipoprotein (LDL) levels; conversely, leptin reversed the aforementioned reaction and was negatively correlated with adiponectin levels. The adiponectin to leptin ratios were significantly lower in PCOS women than in those without PCOS. Compared to women with non-PCOS, overweight/obese women with PCOS had lower serum adiponectin levels than women without PCOS, which was not the case for lean women. Conversely, lean women with PCOS had higher serum leptin levels than those without PCOS, which was not the case for overweight/obese women. Adipose tissue might play an important role in the metabolic complications in women with PCOS. To study the impact of obesity biomarkers in women with PCOS, overweight/obese and lean women should be considered separately.

Plasma adiponectin concentrations are associated with dietary glycemic index in Malaysian patients with type 2 diabetes.

PubMed

Loh, Beng-In; Sathyasuryan, Daniel Robert; Mohamed, Hamid Jan Jan

2013-01-01

Adiponectin, an adipocyte-derived hormone has been implicated in the control of blood glucose and chronic inflammation in type 2 diabetes. However, limited studies have evaluated dietary factors on plasma adiponectin levels, especially among type 2 diabetic patients in Malaysia. The aim of this study was to investigate the influence of dietary glycemic index on plasma adiponectin concentrations in patients with type 2 diabetes. A cross-sectional study was conducted in 305 type 2 diabetic patients aged 19-75 years from the Penang General Hospital, Malaysia. Socio-demographic information was collected using a standard questionnaire while dietary details were determined by using a pre-validated semi-quantitative food frequency questionnaire. Anthropometry measurement included weight, height, BMI and waist circumference. Plasma adiponectin concentrations were measured using a commercial ELISA kit. Data were analyzed using multiple linear regression. After multivariate adjustment, dietary glycemic index was inversely associated with plasma adiponectin concentrations (β =-0.272, 95% CI -0.262, - 0.094; p<0.001). It was found that in individuals who consumed 1 unit of foods containing high dietary glycemic index that plasma adiponectin level reduced by 0.3 μg/mL. Thirty two percent (31.9%) of the variation in adiponectin concentrations was explained by age, sex, race, smoking status, BMI, waist circumference, HDL-C, triglycerides, magnesium, fiber and dietary glycemic index according to the multiple linear regression model (R2=0.319). These results support the hypothesis that dietary glycemic index influences plasma adiponectin concentrations in patients with type 2 diabetes. Controlled clinical trials are required to confirm our findings and to elucidate the underlying mechanism.

Effects of Ramadan fasting on glucose homeostasis and adiponectin levels in healthy adult males.

PubMed

Gnanou, Justin V; Caszo, Brinnell A; Khalil, Khalifah M; Abdullah, Shahidah L; Knight, Victor F; Bidin, Mohd Z

2015-01-01

Adiponectin is a hormone secreted by adipocytes during the fasting phase of the fast-fed cycle. Ramadan fasting involves prolonged fasting for up to twelve hours and thus could lead to increased secretion of adiponectin by adipocytes. However, studies on the role of adiponectin on glucose and body weight homeostasis during Ramadan fasting is still a matter of controversy. Thus the specific aim of this study was to assess the effect of fasting during Ramadan on the adiponectin levels, body weight and glucose homeostasis in healthy male Malaysian subjects. Twenty healthy male (19-23 years) Muslim subjects were followed up during the fasting month of Ramadan. Anthropometry and blood samples were taken one week before and during the fourth week of fasting. Plasma glucose, insulin and adiponectin were estimated and insulin sensitivity indices were estimated using the Homeostasis Model Assessment. Subjects experienced a significant decrease in body weight (2.4 %, p < 0.001) and body mass index (5.5 %, p < 0.01). There was also a significant decrease of 12.3 %, 52.8 % and 45.6 % of plasma glucose, insulin and adiponectin respectively (p < 0.01). The drop in adiponectin was positively correlated with the decrease in body weight (r = 0.45, p < 0.05). There was also a significant increase in insulin sensitivity and a decrease in insulin resistance (p < 0.01). These results indicate that Ramadan fasting in young healthy individuals has a positive impact on the maintenance of glucose homeostasis. It also shows that adiponectin levels dropped along with significant loss in weight. We feel caloric restriction during the Ramadan fasting is in itself sufficient to improve insulin sensitivity in healthy individuals.

Association of CDH13 Genotypes/Haplotypes with Circulating Adiponectin Levels, Metabolic Syndrome, and Related Metabolic Phenotypes: The Role of the Suppression Effect

PubMed Central

Teng, Ming-Sheng; Hsu, Lung-An; Wu, Semon; Sun, Yu-Chen; Juan, Shu-Hui; Ko, Yu-Lin

2015-01-01

Objective Previous genome-wide association studies have indicated an association between CDH13 genotypes and adiponectin levels. In this study, we used mediation analysis to assess the statistical association between CDH13 locus variants and adiponectin levels, metabolic syndrome, and related metabolic phenotypes. Methods and results A sample population of 530 Taiwanese participants was enrolled. Four CDH13 gene variants in the promoter and intron 1 regions were genotyped. After adjustment for clinical covariates, the CDH13 genotypes/haplotypes exhibited an association with the adiponectin levels (lowest P = 1.95 × 10−11 for rs4783244 and lowest P = 3.78 × 10−13 for haplotype ATTT). Significant correlations were observed between the adiponectin levels and the various metabolic syndrome-related phenotypes (all P ≤ 0.005). After further adjustment for the adiponectin levels, participants with a minor allele of rs12051272 revealed a considerable association with a more favorable metabolic profile, including higher insulin sensitivity, high-density lipoprotein cholesterol levels, lower diastolic blood pressure, circulating levels of fasting plasma glucose, and triglycerides, and as a lower risk of metabolic syndrome (all P < 0.05). The mediation analysis further revealed a suppression effect of the adiponectin levels on the association between CDH13 genotypes and metabolic syndrome and its related phenotypes (Sobel test; all P < 0.001). Conclusion The genetic polymorphisms at the CDH13 locus independently affect the adiponectin levels, whereas the adiponectin levels exhibit a suppressive effect on the association between CDH13 locus variants and various metabolic phenotypes and metabolic syndrome. In addition, these results provide further evidence of the association between the CDH13 gene variants and the risks of metabolic syndrome and atherosclerotic cardiovascular disease. PMID:25875811

Baseline adiponectin levels do not influence the response to pioglitazone in ACT NOW.

PubMed

Tripathy, Devjit; Clement, Stephen C; Schwenke, Dawn C; Banerji, MaryAnn; Bray, George A; Buchanan, Thomas A; Gastaldelli, Amalia; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Ratner, Robert E; Stentz, Frankie B; Musi, Nicolas; Reaven, Peter D; DeFronzo, Ralph A

2014-06-01

Plasma adiponectin levels are reduced in type 2 diabetes mellitus (T2DM) and other insulin-resistant states. We examined whether plasma adiponectin levels at baseline and after pioglitazone treatment in impaired glucose tolerance (IGT) subjects were associated with improved insulin sensitivity (SI) and glucose tolerance status. A total of 602 high-risk IGT subjects in ACT NOW were randomized to receive pioglitazone or placebo with a median follow-up of 2.4 years. Pioglitazone reduced IGT conversion to diabetes by 72% in association with improved β-cell function by 64% (insulin secretion/insulin resistance index) and increased tissue sensitivity by 88% (Matsuda index). In pioglitazone-treated subjects, plasma adiponectin concentration increased threefold from 13 ± 0.5 to 38 ± 2.5 μg/mL (P < 0.001) and was strongly correlated with the improvement in SI (r = 0.436, P < 0.001) and modestly correlated with glucose area under the curve during oral glucose tolerance test (r = 0.238, P < 0.005) and insulin secretion/insulin resistance index (r = 0.306, P < 0.005). The increase in adiponectin was a strong predictor of reversion to normal glucose tolerance and prevention of T2DM. In the placebo group, plasma adiponectin did not change and was not correlated with changes in glucose levels. There was an inverse association between baseline plasma adiponectin concentration and progression to diabetes in the placebo group but not in the pioglitazone group. Baseline adiponectin does not predict the response to pioglitazone. The increase in plasma adiponectin concentration after pioglitazone therapy in IGT subjects is strongly related to improved glucose tolerance status and enhanced tissue sensitivity to insulin. © 2014 by the American Diabetes Association.

Baseline Adiponectin Levels Do Not Influence the Response to Pioglitazone in ACT NOW

PubMed Central

Tripathy, Devjit; Clement, Stephen C.; Schwenke, Dawn C.; Banerji, MaryAnn; Bray, George A.; Buchanan, Thomas A.; Gastaldelli, Amalia; Henry, Robert R.; Kitabchi, Abbas E.; Mudaliar, Sunder; Ratner, Robert E.; Stentz, Frankie B.; Musi, Nicolas; Reaven, Peter D.

2014-01-01

OBJECTIVE Plasma adiponectin levels are reduced in type 2 diabetes mellitus (T2DM) and other insulin-resistant states. We examined whether plasma adiponectin levels at baseline and after pioglitazone treatment in impaired glucose tolerance (IGT) subjects were associated with improved insulin sensitivity (SI) and glucose tolerance status. RESEARCH DESIGN AND METHODS A total of 602 high-risk IGT subjects in ACT NOW were randomized to receive pioglitazone or placebo with a median follow-up of 2.4 years. RESULTS Pioglitazone reduced IGT conversion to diabetes by 72% in association with improved β-cell function by 64% (insulin secretion/insulin resistance index) and increased tissue sensitivity by 88% (Matsuda index). In pioglitazone-treated subjects, plasma adiponectin concentration increased threefold from 13 ± 0.5 to 38 ± 2.5 μg/mL (P < 0.001) and was strongly correlated with the improvement in SI (r = 0.436, P < 0.001) and modestly correlated with glucose area under the curve during oral glucose tolerance test (r = 0.238, P < 0.005) and insulin secretion/insulin resistance index (r = 0.306, P < 0.005). The increase in adiponectin was a strong predictor of reversion to normal glucose tolerance and prevention of T2DM. In the placebo group, plasma adiponectin did not change and was not correlated with changes in glucose levels. There was an inverse association between baseline plasma adiponectin concentration and progression to diabetes in the placebo group but not in the pioglitazone group. CONCLUSIONS Baseline adiponectin does not predict the response to pioglitazone. The increase in plasma adiponectin concentration after pioglitazone therapy in IGT subjects is strongly related to improved glucose tolerance status and enhanced tissue sensitivity to insulin. PMID:24705615

Adiponectin regulates thermal nociception in a mouse model of neuropathic pain.

PubMed

Sun, L; Li, H; Tai, L W; Gu, P; Cheung, C W

2018-06-01

Adiponectin, a cytokine secreted by adipocytes, plays an important role in regulating glucose and lipid metabolism. However, the role of adiponectin in pain conditions is largely unknown. This study aimed to identify the role and mechanism of adiponectin in nociceptive sensitivity under physiological and pathological states utilising adiponectin knockout (KO) mice. Wild type (WT) and adiponectin KO mice were subjected to partial sciatic nerve ligation (pSNL) or sham operation. Pain-like behavioural tests, including thermal allodynia, hyperalgesia, and mechanical allodynia, were performed before and after pSNL from Day 3-21. Dorsal root ganglions (DRGs), lumbar spinal segments at L3-5, and somatosensory cortex were collected for protein measurement via western blotting and immunofluorescence staining. Compared with WT mice, KO mice had significantly lower (40-50%) paw withdrawal latency to innocuous and noxious stimuli before and after pSNL. In DRG neurones from KO mice, where adiponectin receptor (AdipoR) 2 is located, phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and heat-sensitive transient receptor potential cation channel subfamily V member 1 (TRPV1) were significantly higher (by two- to three-fold) than from WT mice. In spinal microglia and somatosensory cortical neurones, where AdipoR1 is mainly located, p-p38 MAPK and TRPV1 were also higher (by two- to three-fold) in KO compared with WT mice, and altered signalling of these molecules was exacerbated (1.2- to 1.3-fold) by pSNL. Our results show that adiponectin regulates thermal nociceptive sensitivity by inhibiting activation of DRG neurones, spinal microglia, and somatosensory cortical neurones in physiological and neuropathic pain states. This study has relevance for patients with adiponectin disorders, such as obesity and diabetes. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Associations of serum adiponectin with skeletal muscle morphology and insulin sensitivity.

PubMed

Ingelsson, Erik; Arnlöv, Johan; Zethelius, Björn; Vasan, Ramachandran S; Flyvbjerg, Allan; Frystyk, Jan; Berne, Christian; Hänni, Arvo; Lind, Lars; Sundström, Johan

2009-03-01

Skeletal muscle morphology and function are strongly associated with insulin sensitivity. The objective of the study was to test the hypothesis that circulating adiponectin is associated with skeletal muscle morphology and that adiponectin mediates the relation of muscle morphology to insulin sensitivity. This was a cross-sectional investigation of 461 men aged 71 yr, participants of the community-based Uppsala Longitudinal Study of Adult Men study. Measures included serum adiponectin, insulin sensitivity measured with euglycemic insulin clamp technique, and capillary density and muscle fiber composition determined from vastus lateralis muscle biopsies. In multivariable linear regression models (adjusting for age, physical activity, fasting glucose, and pharmacological treatment for diabetes), serum adiponectin levels rose with increasing capillary density (beta, 0.30 per 50 capillaries per square millimeter increase; P = 0.041) and higher proportion of type I muscle fibers (beta, 0.27 per 10% increase; P = 0.036) but declined with a higher proportion of type IIb fibers (beta, -0.39 per 10% increase; P = 0.014). Using bootstrap methods to examine the potential role of adiponectin in associations between muscle morphology and insulin sensitivity and the associations of capillary density (beta difference, 0.041; 95% confidence interval 0.001, 0.085) and proportion of type IIb muscle fibers (beta difference, -0.053; 95% confidence interval -0.107, -0.002) with insulin sensitivity were significantly attenuated when adiponectin was included in the models. Circulating adiponectin concentrations were higher with increasing skeletal muscle capillary density and in individuals with higher proportion of slow oxidative muscle fibers. Furthermore, our results indicate that adiponectin could be a partial mediator of the relations between skeletal muscle morphology and insulin sensitivity.

Impact of maternal probiotic-supplemented dietary counseling during pregnancy on colostrum adiponectin concentration: a prospective, randomized, placebo-controlled study.

PubMed

Luoto, Raakel; Laitinen, Kirsi; Nermes, Merja; Isolauri, Erika

2012-06-01

The breast milk bioactive substances such as adiponectin, have a presumably long-term impact upon the health and well-being of a child. To determine the impact of probiotic-supplemented dietary counseling during pregnancy on colostrum adiponectin concentration. Altogether 256 pregnant women were randomized into three study groups: dietary intervention with probiotics (diet/probiotics) or with placebo (diet/placebo) and a control group (control/placebo). The intervention group received dietary counseling provided by a nutritionist, the main focus being the amount and the type of dietary fat. The probiotics used were Lactobacillus rhamnosus GG and Bifidobacterium lactis in combination. Dietary intake was evaluated by food records at every trimester of pregnancy. Breast milk samples were collected after birth (colostrum) for adiponectin concentration analysis (n=181). The dietary intervention increased the colostrum adiponectin concentration (ng/mL, geometric mean [95% CI]), the difference being significant when comparing to the control group; 12.7 [10.6-29.7] vs. 10.2 [9.9-13.2], P=0.024. Maternal weight gain during pregnancy (kg) correlated inversely with colostrum adiponectin concentration; β (SE)=-1.7 (0.1), P=0.020, and gestational diabetes mellitus was associated with the likelihood of adiponectin concentration falling into the lowest quartile; OR 2.36, 95% CI 1.1-3.2, P=0.028. In showing that the colostrum adiponectin concentration is markedly dependent on maternal diet and nutritional status during pregnancy, and considering that colostrum adiponectin has potential effects on metabolism, nutrition, and immune function in the neonates, the results of this study underscore the importance of the metabolic homeostasis of the mother for the child's initial nutritional environment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Adiponectin regulates contextual fear extinction and intrinsic excitability of dentate gyrus granule neurons through AdipoR2 receptors

PubMed Central

Zhang, D; Wang, X; Wang, B; Garza, J C; Fang, X; Wang, J; Scherer, P E; Brenner, R; Zhang, W; Lu, X-Y

2017-01-01

Post-traumatic stress disorder (PTSD) is characterized by exaggerated fear expression and impaired fear extinction. The underlying molecular and cellular mechanisms of PTSD are largely unknown. The current pharmacological and non-pharmacological treatments for PTSD are either ineffective or temporary with high relapse rates. Here we report that adiponectin-deficient mice exhibited normal contextual fear conditioning but displayed slower extinction learning. Infusions of adiponectin into the dentate gyrus (DG) of the hippocampus in fear-conditioned mice facilitated extinction of contextual fear. Whole-cell patch-clamp recordings in brain slices revealed that intrinsic excitability of DG granule neurons was enhanced by adiponectin deficiency and suppressed after treatment with the adiponectin mimetic AdipoRon, which were associated with increased input resistance and hyperpolarized resting membrane potential, respectively. Moreover, deletion of AdipoR2, but not AdipoR1 in the DG, resulted in augmented fear expression and reduced extinction, accompanied by intrinsic hyperexcitability of DG granule neurons. Adiponectin and AdipoRon failed to induce facilitation of fear extinction and elicit inhibition of intrinsic excitability of DG neurons in AdipoR2 knockout mice. These results indicated that adiponectin action via AdipoR2 was both necessary and sufficient for extinction of contextual fear and intrinsic excitability of DG granule neurons, implying that enhancing or dampening DG neuronal excitability may cause resistance to or facilitation of extinction. Therefore, our findings provide a functional link between adiponectin/AdipoR2 activation, DG neuronal excitability and contextual fear extinction, and suggest that targeting adiponectin/AdipoR2 may be used to strengthen extinction-based exposure therapies for PTSD. PMID:27137743

Adiponectin expression in subcutaneous adipose tissue is reduced in women with cellulite.

PubMed

Emanuele, Enzo; Minoretti, Piercarlo; Altabas, Karmela; Gaeta, Elio; Altabas, Velimir

2011-04-01

Cellulite, which appears as orange peel-type or cottage cheese-like dimpling of the skin on the thighs and buttocks, is a complex, multifactorial, cosmetic disorder of the subcutaneous fat layer and the overlying superficial skin. Adiponectin is an adipocyte-derived hormone mainly produced by subcutaneous fat that shows important protective anti-inflammatory and vasodilatory effects. We hypothesized that adiponectin expressed in the subcutaneous adipose tissue (SAT) might play a role in the pathogenesis of cellulite. We reasoned that a reduction in the expression of adiponectin - a humoral vasodilator - in the SAT of cellulite areas might contribute to the altered microcirculation frequently found in these regions. A total of 15 lean (body mass index [BMI] < 25 kg/m(2) ) women with cellulite and 15 age- and BMI-matched women without cellulite participated in this study. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to assess adiponectin gene expression. Plasma adiponectin levels were measured using a commercial enzyme immunoassay kit. Adiponectin mRNA expression in the SAT of the gluteal region was significantly lower in areas with cellulite compared with those without (12.6 ± 3.1 AU versus 16.6 ± 4.1 AU; P=0.006). However, plasma adiponectin levels did not differ between women with (20.3 ± 7.3 μg/ml) and without (19.3 ± 6.1 μg/ml) cellulite (P=0.69). Adiponectin expression is significantly reduced in the SAT in areas affected by cellulite. Our findings provide novel insights into the nature of cellulite and may give clues to the treatment of this cosmetic issue. © 2011 The International Society of Dermatology.

Inhibition of leptin-induced vascular extracellular matrix remodelling by adiponectin.

PubMed

Zhang, Zhi; Wang, Fang; Wang, Bing-Jian; Chu, Guang; Cao, Qunan; Sun, Bao-Gui; Dai, Qiu-Yan

2014-10-01

Vascular extracellular matrix (ECM) remodelling, which is the result of disruption in the balance of ECM synthesis and degradation, induces vessel fibrosis and thereby leads to hypertension. Leptin is known to promote tissue fibrosis, while adiponectin has recently been demonstrated to be anti-fibrogenic in tissue fibrosis. In this study, we aimed to evaluate the leptin-antagonist function of adiponectin and to further elucidate the mechanisms through which adiponectin dampens leptin signalling in vascular smooth muscle cells, thus preventing excess ECM production, in our already established 3D co-culture vessel models. Our 3D co-culture vessel model, which mimics true blood vessels, is composed of vascular endothelial cells, vascular smooth muscle cells and collagen type I. We validated the profibrogenic effects of leptin and analysed matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor of metalloproteinase 1 (TIMP1) and collagen types II/IV secretion in 3D vessel models. The protective/inhibitory effects of adiponectin were re-analysed by inhibiting adiponectin receptor 1 (AdipoR) and AdipoR2 expression in endothelial cells using RNAi technology. In the 3D vessel models, adiponectin blocked the leptin-stimulated secretion of collagen types II/IV and TIMP1 while significantly increasing MMP2/9 activity. In endothelial cells, adiponectin induced phosphorylation of AMPK, thereby suppressing leptin-mediated STAT3 phosphorylation through induction of SOCS3 in smooth muscle cells. Our findings indicate that adiponectin disrupted the leptin-induced vascular ECM remodelling via AdipoR1 and enhanced AMPK signalling in endothelial cells, which, in turn, promoted SOCS3 up-regulation in smooth muscle cells to repress leptin-stimulated phosphorylation of STAT3. © 2014 The authors.

Inhibition of leptin-induced vascular extracellular matrix remodelling by adiponectin

PubMed Central

Zhang, Zhi; Wang, Fang; Wang, Bing-jian; Chu, Guang; Cao, Qunan; Sun, Bao-Gui; Dai, Qiu-Yan

2014-01-01

Vascular extracellular matrix (ECM) remodelling, which is the result of disruption in the balance of ECM synthesis and degradation, induces vessel fibrosis and thereby leads to hypertension. Leptin is known to promote tissue fibrosis, while adiponectin has recently been demonstrated to be anti-fibrogenic in tissue fibrosis. In this study, we aimed to evaluate the leptin-antagonist function of adiponectin and to further elucidate the mechanisms through which adiponectin dampens leptin signalling in vascular smooth muscle cells, thus preventing excess ECM production, in our already established 3D co-culture vessel models. Our 3D co-culture vessel model, which mimics true blood vessels, is composed of vascular endothelial cells, vascular smooth muscle cells and collagen type I. We validated the profibrogenic effects of leptin and analysed matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor of metalloproteinase 1 (TIMP1) and collagen types II/IV secretion in 3D vessel models. The protective/inhibitory effects of adiponectin were re-analysed by inhibiting adiponectin receptor 1 (AdipoR) and AdipoR2 expression in endothelial cells using RNAi technology. In the 3D vessel models, adiponectin blocked the leptin-stimulated secretion of collagen types II/IV and TIMP1 while significantly increasing MMP2/9 activity. In endothelial cells, adiponectin induced phosphorylation of AMPK, thereby suppressing leptin-mediated STAT3 phosphorylation through induction of SOCS3 in smooth muscle cells. Our findings indicate that adiponectin disrupted the leptin-induced vascular ECM remodelling via AdipoR1 and enhanced AMPK signalling in endothelial cells, which, in turn, promoted SOCS3 up-regulation in smooth muscle cells to repress leptin-stimulated phosphorylation of STAT3. PMID:24982243

Influence of Adiponectin Gene Polymorphisms on Adiponectin Level and Insulin Resistance Index in Response to Dietary Intervention in Overweight-Obese Patients With Impaired Fasting Glucose or Newly Diagnosed Type 2 Diabetes

PubMed Central

Chung, Hye Kyung; Chae, Jey Sook; Hyun, Yae Jung; Paik, Jean Kyung; Kim, Ji Young; Jang, Yangsoo; Kwon, Hyuck Moon; Song, Young Duk; Lee, Hyun Chul; Lee, Jong Ho

2009-01-01

OBJECTIVE The aim of this study was to determine the effect of common adiponectin gene polymorphisms on dietary intervention-mediated changes in adiponectin levels and homeostasis model assessment of insulin resistance (HOMA-IR) indexes. RESEARCH DESIGN AND METHODS A total of 363 subjects with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes followed a dietary intervention (replacement of cooked refined rice with whole grains and an increase in vegetable intake) and regular walking for 12 weeks without any medication. Adiponectin gene single nucleotide polymorphisms (SNPs) (45, 276, and −11377) were examined in these subjects. RESULTS After this dietary intervention, fasting glucose levels decreased in all three SNP 45T>G genotype groups. Subjects with the SNP 45TT genotype showed increased adiponectin levels and decreased HOMA-IR indexes. Haplotype analysis revealed that homozygous carriers of the TG haplotype (45TT and 276GG) and heterozygous carriers of the TG haplotype (TG/X) showed a reduction in the HOMA-IR index after adjustment for baseline levels. Significant differences were observed in changes in HOMA-IR indexes and adiponectin concentrations according to the 45-276 TG haplotype in overweight-obese, but not in normal-weight subjects: the greatest decrease in HOMA-IR indexes and the greatest increase in adiponectin levels were shown in overweight-obese subjects with the TG/TG haplotype. CONCLUSIONS ADIPOQ genetic variants can affect circulating adiponectin levels and insulin resistance indexes in subjects with IFG or newly diagnosed type 2 diabetes in response to dietary intervention. PMID:19131459

Serum levels of adiponectin and leptin as biomarkers of proteinuria in lupus nephritis.

PubMed

Diaz-Rizo, Valeria; Bonilla-Lara, David; Gonzalez-Lopez, Laura; Sanchez-Mosco, Dalia; Fajardo-Robledo, Nicte S; Perez-Guerrero, Edsaul E; Rodriguez-Jimenez, N Alejandra; Saldaña-Cruz, A Miriam; Vazquez-Villegas, M Luisa; Gomez-Bañuelos, Eduardo; Vazquez-Del Mercado, Monica; Cardona-Muñoz, E German; Cardona-Muller, David; Trujillo, Xochitl; Huerta, Miguel; Salazar-Paramo, Mario; Gamez-Nava, Jorge I

2017-01-01

There are controversial results about the role of serum leptin and adiponectin levels as biomarkers of the severity of proteinuria in lupus nephritis. The aim of this study was to evaluate the relationship between serum leptin and adiponectin levels with severity of proteinuria secondary to lupus nephritis (LN). In a cross-sectional study, 103 women with systemic lupus erythematosus (SLE) were evaluated for kidney involvement. We compared 30 SLE patients with LN, all of them with proteinuria, versus 73 SLE patients without renal involvement (no LN). A comprehensive set of clinical and laboratory variables was assessed, including serum levels of leptin and adiponectin by ELISA. Multivariate analyses were used to adjust for potential confounders associated with proteinuria in LN. We found higher adiponectin levels in the LN group compared with the no LN group (20.4 ± 10.3 vs 15.6 ± 7.8 μg/mL; p = 0.02), whereas no differences were observed in leptin levels (33.3 ± 31.4 vs 22.5 ± 25.5 ng/mL; p = 0.07). Severity of proteinuria correlated with an increase in adiponectin levels (r = 0.31; p = 0.001), but no correlation was observed with leptin. Adiponectin levels were not related to anti-dsDNA or anti-nucleosome antibodies. In the logistic regression, adiponectin levels were associated with a high risk of proteinuria in SLE (OR = 1.06; 95% CI 1.01-1.12; p = 0.02). Instead, leptin was not associated with LN. These findings indicate that adiponectin levels are useful markers associated with proteinuria in LN. Further longitudinal studies are required to identify if these levels are predictive of renal relapse.

Serum levels of adiponectin and leptin as biomarkers of proteinuria in lupus nephritis

PubMed Central

Sanchez-Mosco, Dalia; Fajardo-Robledo, Nicte S.; Perez-Guerrero, Edsaul E.; Rodriguez-Jimenez, N. Alejandra; Saldaña-Cruz, A. Miriam; Vazquez-Villegas, M. Luisa; Gomez-Bañuelos, Eduardo; Vazquez-Del Mercado, Monica; Cardona-Muñoz, E. German; Cardona-Muller, David; Trujillo, Xochitl; Huerta, Miguel; Salazar-Paramo, Mario

2017-01-01

Introduction There are controversial results about the role of serum leptin and adiponectin levels as biomarkers of the severity of proteinuria in lupus nephritis. Objective The aim of this study was to evaluate the relationship between serum leptin and adiponectin levels with severity of proteinuria secondary to lupus nephritis (LN). Methods In a cross-sectional study, 103 women with systemic lupus erythematosus (SLE) were evaluated for kidney involvement. We compared 30 SLE patients with LN, all of them with proteinuria, versus 73 SLE patients without renal involvement (no LN). A comprehensive set of clinical and laboratory variables was assessed, including serum levels of leptin and adiponectin by ELISA. Multivariate analyses were used to adjust for potential confounders associated with proteinuria in LN. Results We found higher adiponectin levels in the LN group compared with the no LN group (20.4 ± 10.3 vs 15.6 ± 7.8 μg/mL; p = 0.02), whereas no differences were observed in leptin levels (33.3 ± 31.4 vs 22.5 ± 25.5 ng/mL; p = 0.07). Severity of proteinuria correlated with an increase in adiponectin levels (r = 0.31; p = 0.001), but no correlation was observed with leptin. Adiponectin levels were not related to anti-dsDNA or anti-nucleosome antibodies. In the logistic regression, adiponectin levels were associated with a high risk of proteinuria in SLE (OR = 1.06; 95% CI 1.01–1.12; p = 0.02). Instead, leptin was not associated with LN. Conclusion These findings indicate that adiponectin levels are useful markers associated with proteinuria in LN. Further longitudinal studies are required to identify if these levels are predictive of renal relapse. PMID:28898254

Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian Randomization analysis using data from three large cohort studies.

PubMed

Nimptsch, Katharina; Song, Mingyang; Aleksandrova, Krasimira; Katsoulis, Michail; Freisling, Heinz; Jenab, Mazda; Gunter, Marc J; Tsilidis, Konstantinos K; Weiderpass, Elisabete; Bueno-De-Mesquita, H Bas; Chong, Dawn Q; Jensen, Majken K; Wu, Chunsen; Overvad, Kim; Kühn, Tilman; Barrdahl, Myrto; Melander, Olle; Jirström, Karin; Peeters, Petra H; Sieri, Sabina; Panico, Salvatore; Cross, Amanda J; Riboli, Elio; Van Guelpen, Bethany; Myte, Robin; Huerta, José María; Rodriguez-Barranco, Miguel; Quirós, José Ramón; Dorronsoro, Miren; Tjønneland, Anne; Olsen, Anja; Travis, Ruth; Boutron-Ruault, Marie-Christine; Carbonnel, Franck; Severi, Gianluca; Bonet, Catalina; Palli, Domenico; Janke, Jürgen; Lee, Young-Ae; Boeing, Heiner; Giovannucci, Edward L; Ogino, Shuji; Fuchs, Charles S; Rimm, Eric; Wu, Kana; Chan, Andrew T; Pischon, Tobias

2017-05-01

Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case-control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623 matched controls), the Health Professionals Follow-up Study (HPFS, 231 cases, 230 controls) and the Nurses' Health Study (NHS, 399 cases, 774 controls) with available data on pre-diagnostic adiponectin concentrations and selected single nucleotide polymorphisms in the ADIPOQ gene. We created an ADIPOQ allele score that explained approximately 3% of the interindividual variation in adiponectin concentrations. The ADIPOQ allele score was not associated with risk of colorectal cancer in logistic regression analyses (pooled OR per score-unit unit 0.97, 95% CI 0.91, 1.04). Genetically determined twofold higher adiponectin was not significantly associated with risk of colorectal cancer using the ADIPOQ allele score as instrumental variable (pooled OR 0.73, 95% CI 0.40, 1.34). In a summary instrumental variable analysis (based on previously published data) with higher statistical power, no association between genetically determined twofold higher adiponectin and risk of colorectal cancer was observed (0.99, 95% CI 0.93, 1.06 in women and 0.94, 95% CI 0.88, 1.01 in men). Thus, our study does not support a causal effect of circulating adiponectin on colorectal cancer risk. Due to the limited genetic determination of adiponectin, larger Mendelian Randomization studies are necessary to clarify whether adiponectin is causally related to lower risk of colorectal cancer.

Adiponectin regulates contextual fear extinction and intrinsic excitability of dentate gyrus granule neurons through AdipoR2 receptors.

PubMed

Zhang, D; Wang, X; Wang, B; Garza, J C; Fang, X; Wang, J; Scherer, P E; Brenner, R; Zhang, W; Lu, X-Y

2017-07-01

Post-traumatic stress disorder (PTSD) is characterized by exaggerated fear expression and impaired fear extinction. The underlying molecular and cellular mechanisms of PTSD are largely unknown. The current pharmacological and non-pharmacological treatments for PTSD are either ineffective or temporary with high relapse rates. Here we report that adiponectin-deficient mice exhibited normal contextual fear conditioning but displayed slower extinction learning. Infusions of adiponectin into the dentate gyrus (DG) of the hippocampus in fear-conditioned mice facilitated extinction of contextual fear. Whole-cell patch-clamp recordings in brain slices revealed that intrinsic excitability of DG granule neurons was enhanced by adiponectin deficiency and suppressed after treatment with the adiponectin mimetic AdipoRon, which were associated with increased input resistance and hyperpolarized resting membrane potential, respectively. Moreover, deletion of AdipoR2, but not AdipoR1 in the DG, resulted in augmented fear expression and reduced extinction, accompanied by intrinsic hyperexcitability of DG granule neurons. Adiponectin and AdipoRon failed to induce facilitation of fear extinction and elicit inhibition of intrinsic excitability of DG neurons in AdipoR2 knockout mice. These results indicated that adiponectin action via AdipoR2 was both necessary and sufficient for extinction of contextual fear and intrinsic excitability of DG granule neurons, implying that enhancing or dampening DG neuronal excitability may cause resistance to or facilitation of extinction. Therefore, our findings provide a functional link between adiponectin/AdipoR2 activation, DG neuronal excitability and contextual fear extinction, and suggest that targeting adiponectin/AdipoR2 may be used to strengthen extinction-based exposure therapies for PTSD.

Normal adiponectin levels despite abnormal glucose tolerance (or diabetes) and inflammation in adult patients with cystic fibrosis.

PubMed

Hammana, I; Malet, A; Costa, M; Brochiero, E; Berthiaume, Y; Potvin, S; Chiasson, J-L; Coderre, L; Rabasa-Lhoret, R

2007-06-01

Circulating adiponectin levels are negatively associated with glucose intolerance, inflammation and central adiposity. Since these conditions are common in cystic fibrosis (CF), we examined whether adiponectin values are altered in these patients. To determine if CF patients have altered adiponectin levels and if these levels correlate with glucose tolerance categories (normal, impaired glucose tolerance (IGT) and cystic fibrosis-related diabetes (CFRD)), insulin resistance or inflammatory markers such as fibrinogen and C-reactive protein (CRP). Oral glucose tolerance tests (OGTTs) were performed and adiponectin levels were measured in 90 CF patients not known to be diabetic and 15 healthy controls matched for age, sex and body mass index (BMI). Inflammatory markers, serum albumin concentrations and the clinical status of CF patients (i.e. pulmonary function) were also examined. CF pathology was characterized by a high prevalence (43.5%) of glucose tolerance abnormalities: 26.5% of IGT and 17.0% of newly diagnosed CFRD. CF patients also presented systemic inflammation as revealed by a significant increase of fibrinogen (P=0.029) in all patients and higher CRP levels in CFRD patients compared to the controls (P<0.05). On the other hand, CF and control subjects had similar albumin serum concentration. While CF patients and controls had similar serum adiponectin values, women had significantly higher hormone levels than men (P<0.001). Adiponectin levels did not correlate with glucose tolerance, inflammatory markers or insulin resistance. On the other hand, they correlated positively with both total and HDL-cholesterol (P<0.001). CF patients did not show any alterations in adiponectin levels despite insulin resistance, glucose intolerance and sub clinical chronic inflammation. Thus, CF appears to be one of the rare conditions in which discordance between adiponectin values and insulin resistance or inflammation is evident.

Association of polymorphism in adiponectin (+45 T/G) and leptin (–2548 G/A) genes with type 2 diabetes mellitus in male Egyptians

PubMed Central

Motawi, Tarek; Salman, Tarek; Shaker, Olfat

2015-01-01

Introduction Adiponectin is an adipose tissue-specific protein with insulin-sensitizing properties. Many investigators have explored the association between adiponectin single nucleotide polymorphisms (SNPs) and type 2 diabetes mellitus (T2DM) in different ethnic populations from different regions. Leptin is a protein hormone constituting an important signal in the regulation of adipose tissue mass and body weight. The aim of this study was to explore potential associations between SNP +45 T>G of the adiponectin gene and SNP 2548G/A of leptin with T2DM and the effect of SNPs on serum adiponectin and leptin levels. Material and methods From the Egyptian population, we enrolled 110 T2DM patients and 90 non-diabetic controls. Serum lipid profile, blood glucose, serum adiponectin, and leptin were measured. Genotyping for two common SNPs of the adiponectin and leptin genes was performed by polymerase chain reaction–restriction fragment length polymorphism. Results The G allele and TG/GG genotype of SNP 45 occurred more frequently than the T allele and TT genotype in T2DM patients compares to the controls. Subjects with the GG + TG genotype of SNP 45 were at increased risk for T2DM (OR = 6.476; 95% CI: 3.401–12.33) and associated with a low serum adiponectin level compared with the TT genotype. The serum leptin concentration of GA + AA genotype carriers was not significantly different from that of the GG genotype in the diabetic group. Conclusions The G allele carriers who have reduced plasma concentrations of adiponectin may have an association with T2DM, while leptin SNP 2548 G/A is not associated with the risk of development of T2DM in the Egyptian population. PMID:26528333

Effects of Quercetin on Adiponectin-Mediated Insulin Sensitivity in Polycystic Ovary Syndrome: A Randomized Placebo-Controlled Double-Blind Clinical Trial.

PubMed

Rezvan, N; Moini, A; Janani, L; Mohammad, K; Saedisomeolia, A; Nourbakhsh, M; Gorgani-Firuzjaee, S; Mazaherioun, M; Hosseinzadeh-Attar, M J

2017-02-01

Polycystic ovary syndrome (PCOS) is a heterogeneous, multi-causal, and genetically complex disorder, which is related to the failure in endocrine glands. Adiponectin has been reported to be low in PCOS, even in the absence of adiposity. Quercetin reduces serum glucose, insulin, triglycerides, and cholesterol levels and increases the expression and secretion of adiponectin. The aim of this study was to determine the effect of quercetin on the adiponectin-mediated insulin sensitivity in PCOS patients. Eighty-four women with PCOS were selected and randomly assigned to 2 groups of treatment and control. The treatment group received 1 g quercetin (two 500 mg capsules) daily for 12 weeks, and the control group received placebo. In addition to anthropometric assessments, fasting serum levels of total adiponectin, high-molecular-weight (HMW) adiponectin, glucose, insulin, testosterone, LH, and SHBG were also measured at the baseline and at the end of the trial. Quercetin could slightly increase the level of adiponectin by 5.56% as compared to placebo (adjusted p-value=0.001) and HMW adiponectin by 3.9% as compared to placebo (adjusted p-value=0.017), while it reduced the level of testosterone (0.71 ng/dl in quercetin vs. 0.77 ng/dl in placebo; p<0.001) and LH (8.42 IU/l in quercetin vs. 8.68 IU/l in placebo; p=0.009). HOMA-IR levels were also significantly (p<0.001) lower in quercetin (1.84) group compared to placebo group (2.21). Oral quercetin supplementation was effective in improving the adiponectin-mediated insulin resistance and hormonal profile of women with PCOS. © Georg Thieme Verlag KG Stuttgart · New York.

Serum adiponectin and resistin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome.

PubMed

Olszanecka-Glinianowicz, Magdalena; Kuglin, Dorota; Dąbkowska-Huć, Anna; Skałba, Piotr

2011-01-01

It seems that adipokines participate in disturbances of the function of the hypothalamus-pituitary-ovary axis. The aim of the study was to assess the relationship between plasma adiponectin and resistin levels and insulin resistance and markers of hyperandrogenism in lean and obese PCOS women. Forty-one women with PCOS (22 lean and 19 obese) and 16 healthy lean women were enrolled. Body mass and height were measured and body mass index was calculated. In addition to serum glucose, lipids, androgens and insulin, adiponectin and resistin concentration were assessed in the fasting state. The insulin resistance was calculated based on the HOMA-IR. Similar serum resistin concentrations were found in both PCOS subgroups and controls. The obese PCOS subgroup was characterized by the lowest serum adiponectin level (10.8 ± 8.3, compared with 21.0 ± 15.1 in the normal weight PCOS subgroup and 26.7 ± 12.5 μg/ml in controls). There were no correlations between resistin and adiponectin levels and HOMA-IR values and serum androgen concentrations. Significant positive correlations between adiponectin to resistin ratio and plasma FSH (r = 0.49; p = 0.001) and LH (r = 0.45; p = 0.003) concentrations, and a negative correlation with free androgen index (r = -0.34; p = 0.03) in PCOS group were found. Obese but not normal weight PCOS women have lower adiponectin levels whereas resistin concentration did not differ in normal weight and obese PCOS compared to control subjects. We hypothesize that changes of the relative proportion of adiponectin to resistin, but not circulating adiponectin and resistin levels themselves, may play a role in hormonal disturbances but not in insulin resistance in PCOS. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The adipokine adiponectin has potent anti-fibrotic effects mediated via adenosine monophosphate-activated protein kinase: novel target for fibrosis therapy

PubMed Central

2012-01-01

Introduction Fibrosis in scleroderma is associated with collagen deposition and myofibroblast accumulation. Peroxisome proliferator activated receptor gamma (PPAR-γ), a master regulator of adipogenesis, inhibits profibrotic responses induced by transforming growth factor-ß (TGF-β), and its expression is impaired in scleroderma. The roles of adiponectin, a PPAR-γ regulated pleiotropic adipokine, in regulating the response of fibroblasts and in mediating the effects of PPAR-γ are unknown. Methods Regulation of fibrotic gene expression and TGF-ß signaling by adiponectin and adenosine monophosphate protein-activated (AMP) kinase agonists were examined in normal fibroblasts in monolayer cultures and in three-dimensional skin equivalents. AdipoR1/2 expression on skin fibroblasts was determined by real-time quantitative PCR. Results Adiponectin, an adipokine directly regulated by PPAR-γ, acts as a potent anti-fibrotic signal in normal and scleroderma fibroblasts that abrogates the stimulatory effects of diverse fibrotic stimuli and reduces elevated collagen gene expression in scleroderma fibroblasts. Adiponectin responses are mediated via AMP kinase, a fuel-sensing cellular enzyme that is necessary and sufficient for down-regulation of fibrotic genes by blocking canonical Smad signaling. Moreover, we demonstrate that endogenous adiponectin accounts, at least in part, for the anti-fibrotic effects exerted by ligands of PPAR-γ. Conclusions These findings reveal a novel link between cellular energy metabolism and extracellular matrix homeostasis converging on AMP kinase. Since the levels of adiponectin as well as its receptor are impaired in scleroderma patients with progressive fibrosis, the present results suggest a potential role for defective adiponectin expression or function in progressive fibrogenesis in scleroderma and other chronic fibrosing conditions. Restoring the adiponectin signaling axis in fibroblasts might, therefore, represent a novel pharmacological approach to controlling fibrosis. PMID:23092446

Globular adiponectin induces a pro-inflammatory response in human astrocytic cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana

Highlights: • Adiponectin receptors are expressed in human astrocytes. • Globular adiponectin induces secretion of IL-6 and MCP-1 from cultured astrocytes. • Adiponectin may play a pro-inflammatory role in astrocytes. - Abstract: Neuroinflammation, mediated in part by activated brain astrocytes, plays a critical role in the development of neurodegenerative disorders, including Alzheimer’s disease (AD). Adiponectin is the most abundant adipokine secreted from adipose tissue and has been reported to exert both anti- and pro-inflammatory effects in peripheral tissues; however, the effects of adiponectin on astrocytes remain unknown. Shifts in peripheral concentrations of adipokines, including adiponectin, could contribute to the observedmore » link between midlife adiposity and increased AD risk. The aim of the present study was to characterize the effects of globular adiponectin (gAd) on pro-inflammatory cytokine mRNA expression and secretion in human U373 MG astrocytic cells and to explore the potential involvement of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphatidylinositide 3-kinases (PI3 K) signaling pathways in these processes. We demonstrated expression of adiponectin receptor 1 (adipoR1) and adipoR2 in U373 MG cells and primary human astrocytes. gAd induced secretion of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and gene expression of IL-6, MCP-1, IL-1β and IL-8 in U373 MG cells. Using specific inhibitors, we found that NF-κB, p38MAPK and ERK1/2 pathways are involved in gAd-induced induction of cytokines with ERK1/2 contributing the most. These findings provide evidence that gAd may induce a pro-inflammatory phenotype in human astrocytes.« less

Adiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction - an experimental study.

PubMed

Fu, Mingqiang; Zhou, Jingmin; Qian, Juying; Jin, Xuejuan; Zhu, Hongmin; Zhong, Chunlin; Fu, Michael; Zou, Yunzeng; Ge, Junbo

2012-08-30

Adiponectin is reported to relate with cardiovascular diseases, we sought to examine whether adiponectin is associated with disease progression of heart failure from hypertension in rats in comparison with other known biomarkers and echocardiographic parameters. Spontaneously hypertensive rats (SHR, n = 35), aged 1 month, were used and followed up to 18 months. High frequency echocardiography was performed both at baseline and every 3 months thereafter. Moreover, serum levels of N-terminal pro-natriuretic peptide (NT-proBNP) and interleukin-6 (IL-6) as well as serum level and tissue expression of adiponectin were determined at the same time as echocardiography. The results clearly demonstrated time-dependent progression of hypertension and heart dysfunction as evidenced by gradually increased left ventricular mass index, NT-proBNP, IL-6 as well as gradually decreased cardiac function as assessed by echocardiography. Meanwhile, tissue and serum adiponectin decreased from 3 months and reached plateau until 12 months in parallel with decreasing of cardiac diastolic function. Thereafter, adiponectin levels increased prior to occurrence of systolic dysfunction. Adiponectin concentration is inversely related with NT-proBNP, IL-6 and E/E' (correlation coefficient (r) = -0.756 for NT-proBNP, p < 0.001, -0.635 for IL-6, p = 0.002, and -0.626 for E/E', p = 0.002, respectively) while positively correlated with E/A and E'/A' (r = 0.683 for E/A, p = 0.001, 0.671 for E'/A', p = 0.001, respectively). No difference for adiponectin distribution among visceral adipose tissues was found. Adiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction.

Increased serum concentrations of adiponectin in canine hypothyroidism.

PubMed

Mazaki-Tovi, Michal; Abood, Sarah K; Kol, Amir; Farkas, Amnon; Schenck, Patricia A

2015-02-01

Serum concentrations of adiponectin were compared between sex-matched hypothyroid (n = 18) and euthyroid (n = 18) client-owned dogs with comparable ages and body condition scores (BCS). Concentrations of adiponectin (mean; 95% confidence interval) were significantly (P < 0.01) higher in hypothyroid (17.2 µg/mL; 12.1-20.5 µg/mL) than healthy (8.0 µg/mL; 5.6-11.4 µg/mL) dogs following adjustment for potential confounders (BCS, age and sex). Serum concentrations of adiponectin were significantly negatively associated with concentrations of total thyroxine (P <0.05) and positively correlated with concentrations of cholesterol (r = 0.6, P <0.01) in hypothyroid dogs. In conclusion, this study demonstrated increased serum concentrations of adiponectin in dogs with hypothyroidism. Suggestive of the presence of resistance to adiponectin that could have contributed to development of hyperlipidemia and insulin resistance in these dogs or alternatively, could be a consequence of these metabolic alterations. Copyright © 2014 Elsevier Ltd. All rights reserved.

The efficacy of adipokines and indices of metabolic syndrome as predictors of severe obesity-related hepatic steatosis.

PubMed

Méndez-Sánchez, Nahum; Chávez-Tapia, Norberto C; Medina-Santillán, Roberto; Villa, Antonio R; Sánchez-Lara, Karla; Ponciano-Rodríguez, Guadalupe; Ramos, Martha H; Uribe, Misael

2006-10-01

The aim of this study was to investigate adiponectin, leptin, and metabolic syndrome as predictors of the severity of obesity-related steatosis. By ultrasonography steatosis-positive (cases) subjects (n = 141) were compared with controls (n = 111). Demographic and anthropometric data and serum concentrations of adiponectin, leptin, and insulin were measured. The impact of several criteria of metabolic syndrome, serum adiponectin concentrations, and serum leptin concentrations were tested using a multivariate logistic regression analysis. The frequency of metabolic syndrome was higher in cases (44.0% versus 9.2%; P < .0001). Cases were older and had higher insulin resistance, waist circumference, and lower concentrations of adiponectin (all P < .001). The upper adiponectin quartile was associated with a lesser grade of steatosis. Metabolic syndrome and adiponectin concentrations were independently associated with the probability of steatosis. In conclusion, adipokines and metabolic syndrome are useful indices for the prediction of the severity of obesity-related steatosis.

Independent associations of total and high molecular weight adiponectin with cardiometabolic risk and surrogate markers of enhanced early atherogenesis in black and white patients with rheumatoid arthritis: a cross-sectional study

PubMed Central

2013-01-01

Introduction Whether adiponectin levels associate with atherogenesis in RA is uncertain. We examined the independent relationships of total and high molecular weight (HMW) adiponectin concentrations with cardiometabolic risk and surrogate markers of enhanced early atherogenesis in black and white patients with RA. Methods We determined total and HMW adiponectin concentrations and those of endothelial activation molecules including soluble E-selectin, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), in 210 (119 black and 91 white) RA patients. Associations were determined in potential confounder and mediator adjusted mixed regression models. Results Total and HMW adiponectin concentrations related similarly to metabolic risk factors and endothelial activation. In all patients, total and HMW adiponectin concentrations associated paradoxically with high systolic, diastolic and mean blood pressure (partial R = 0.155 to 0.241, P ≤0.03). Ethnic origin did not impact on these relationships (interaction P ≥0.09). Total and HMW adiponectin concentrations associated with those of glucose in white and black patients respectively (partial R = -0.304, P = 0.006 and -0.246, P = 0.01). In black but not white participants, total and HMW adiponectin concentrations also related favorably to lipid profiles (partial R = 0.292 to 0.360, P ≤0.003 for HDL cholesterol concentrations, -0.269 to -0.299, P ≤0.006 for triglyceride concentrations and -0.302 to -0.390, P ≤0.002 for total-HDL cholesterol ratio) and the number of metabolic risk factors (partial R = -0.210 to -0.238, P ≤0.03). In white but not black patients, total and HMW adiponectin concentrations associated paradoxically with overall endothelial activation as estimated by a standard z-score of endothelial activation molecule concentrations (partial R = 0.262, P = 0.01 and 0.252, P = 0.02); in the respective models, the extent of effect of total and HMW adiponectin concentrations on endothelial activation was larger in white compared to black participants (standardized β (SE) = 0.260 (0.107) versus -0.106 (0.107), P = 0.01 and 0.260 (0.120) versus -0.100 (0.111), P = 0.02). The HMW-total adiponectin ratio related inconsistently to metabolic risk factors and not to endothelial activation. Conclusion In this study, total and HMW adiponectin concentrations associated with increased blood pressure parameters, and in white patients additionally with endothelial activation. The potential mechanism(s) underlying these paradoxical relationships between adiponectin concentrations and cardiovascular risk in RA merit further investigation. PMID:24286214

Independent associations of total and high molecular weight adiponectin with cardiometabolic risk and surrogate markers of enhanced early atherogenesis in black and white patients with rheumatoid arthritis: a cross-sectional study.

PubMed

Dessein, Patrick H; Woodiwiss, Angela J; Norton, Gavin R; Tsang, Linda; Solomon, Ahmed

2013-09-20

Whether adiponectin levels associate with atherogenesis in RA is uncertain. We examined the independent relationships of total and high molecular weight (HMW) adiponectin concentrations with cardiometabolic risk and surrogate markers of enhanced early atherogenesis in black and white patients with RA. We determined total and HMW adiponectin concentrations and those of endothelial activation molecules including soluble E-selectin, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), in 210 (119 black and 91 white) RA patients. Associations were determined in potential confounder and mediator adjusted mixed regression models. Total and HMW adiponectin concentrations related similarly to metabolic risk factors and endothelial activation. In all patients, total and HMW adiponectin concentrations associated paradoxically with high systolic, diastolic and mean blood pressure (partial R = 0.155 to 0.241, P ≤ 0.03). Ethnic origin did not impact on these relationships (interaction P ≥ 0.09). Total and HMW adiponectin concentrations associated with those of glucose in white and black patients respectively (partial R = -0.304, P = 0.006 and -0.246, P = 0.01). In black but not white participants, total and HMW adiponectin concentrations also related favorably to lipid profiles (partial R = 0.292 to 0.360, P ≤ 0.003 for HDL cholesterol concentrations, -0.269 to -0.299, P ≤ 0.006 for triglyceride concentrations and -0.302 to -0.390, P ≤ 0.002 for total-HDL cholesterol ratio) and the number of metabolic risk factors (partial R = -0.210 to -0.238, P ≤ 0.03). In white but not black patients, total and HMW adiponectin concentrations associated paradoxically with overall endothelial activation as estimated by a standard z-score of endothelial activation molecule concentrations (partial R = 0.262, P = 0.01 and 0.252, P = 0.02); in the respective models, the extent of effect of total and HMW adiponectin concentrations on endothelial activation was larger in white compared to black participants (standardized β (SE) = 0.260 (0.107) versus -0.106 (0.107), P = 0.01 and 0.260 (0.120) versus -0.100 (0.111), P = 0.02). The HMW-total adiponectin ratio related inconsistently to metabolic risk factors and not to endothelial activation. In this study, total and HMW adiponectin concentrations associated with increased blood pressure parameters, and in white patients additionally with endothelial activation. The potential mechanism(s) underlying these paradoxical relationships between adiponectin concentrations and cardiovascular risk in RA merit further investigation.

Fat-Specific DsbA-L Overexpression Promotes Adiponectin Multimerization and Protects Mice From Diet-Induced Obesity and Insulin Resistance

PubMed Central

Liu, Meilian; Xiang, Ruihua; Wilk, Sarah Ann; Zhang, Ning; Sloane, Lauren B.; Azarnoush, Kian; Zhou, Lijun; Chen, Hongzhi; Xiang, Guangda; Walter, Christi A.; Austad, Steven N.; Musi, Nicolas; DeFronzo, Ralph A.; Asmis, Reto; Scherer, Philipp E.; Dong, Lily Q.; Liu, Feng

2012-01-01

The antidiabetic and antiatherosclerotic effects of adiponectin make it a desirable drug target for the treatment of metabolic and cardiovascular diseases. However, the adiponectin-based drug development approach turns out to be difficult due to extremely high serum levels of this adipokine. On the other hand, a significant correlation between adiponectin multimerization and its insulin-sensitizing effects has been demonstrated, suggesting a promising alternative therapeutic strategy. Here we show that transgenic mice overexpressing disulfide bond A oxidoreductase-like protein in fat (fDsbA-L) exhibited increased levels of total and the high-molecular-weight form of adiponectin compared with wild-type (WT) littermates. The fDsbA-L mice also displayed resistance to diet-induced obesity, insulin resistance, and hepatic steatosis compared with WT control mice. The protective effects of DsbA-L overexpression on diet-induced insulin resistance, but not increased body weight and fat cell size, were significantly decreased in adiponectin-deficient fDsbA-L mice (fDsbA-L/Ad−/−). In addition, the fDsbA-L/Ad−/− mice displayed greater activity and energy expenditure compared with adiponectin knockout mice under a high-fat diet. Taken together, our results demonstrate that DsbA-L protects mice from diet-induced obesity and insulin resistance through adiponectin-dependent and independent mechanisms. In addition, upregulation of DsbA-L could be an effective therapeutic approach for the treatment of obesity and its associated metabolic disorders. PMID:22807031

Nicotinic Acid Increases Adiponectin Secretion from Differentiated Bovine Preadipocytes through G-Protein Coupled Receptor Signaling

PubMed Central

Kopp, Christina; Hosseini, Afshin; Singh, Shiva P.; Regenhard, Petra; Khalilvandi-Behroozyar, Hamed; Sauerwein, Helga; Mielenz, Manfred

2014-01-01

The transition period in dairy cows (3 weeks prepartum until 3 weeks postpartum) is associated with substantial mobilization of energy stores, which is often associated with metabolic diseases. Nicotinic acid (NA) is an antilipolytic and lipid-lowering compound used to treat dyslipidaemia in humans, and it also reduces non-esterified fatty acids in cattle. In mice the G-protein coupled receptor 109A (GPR109A) ligand NA positively affects the secretion of adiponectin, an important modulator of glucose and fat metabolism. In cattle, the corresponding data linking NA to adiponectin are missing. Our objective was to examine the effects of NA on adiponectin and AMPK protein abundance and the expression of mRNAs of related genes such as chemerin, an adipokine that enhances adiponectin secretion in vitro. Differentiated bovine adipocytes were incubated with pertussis toxin (PTX) to verify the involvement of GPR signaling, and treated with 10 or 15 µM NA for 12 or 24 h. NA increased adiponectin concentrations (p ≤ 0.001) and the mRNA abundances of GPR109A (p ≤ 0.05) and chemerin (p ≤ 0.01). Pre-incubation with PTX reduced the adiponectin response to NA (p ≤ 0.001). The NA-stimulated secretion of adiponectin and the mRNA expression of chemerin in the bovine adipocytes were suggestive of GPR signaling-dependent improved insulin sensitivity and/or adipocyte metabolism in dairy cows. PMID:25411802

Adiponectin influences progesterone production from MA-10 Leydig cells in a dose-dependent manner.

PubMed

Landry, David; Paré, Aurélie; Jean, Stéphanie; Martin, Luc J

2015-04-01

Obesity in men is associated with lower testosterone levels, related to reduced sperm concentration and the development of various diseases with aging. Hormones produced by the adipose tissue may have influences on both metabolism and reproductive function. Among them, the production and secretion of adiponectin is inversely correlated to total body fat. Adiponectin receptors (AdipoR1 and AdipoR2) have been found to be expressed in testicular Leydig cells (producing testosterone). Since StAR and Cyp11a1 are essential for testosterone synthesis and adiponectin has been shown to regulate StAR mRNA in swine granulosa cells, we hypothesized that adiponectin might also regulate these genes in Leydig cells. Our objective was to determine whether adiponectin regulates StAR and Cyp11a1 genes in Leydig cells and to better define its mechanisms of action. Methods used in the current study are qPCR for the mRNA levels, transfections for promoter activities, and enzyme-linked immunosorbent assay for the progesterone concentration. We have found that adiponectin cooperates with cAMP-dependent stimulation to activate StAR and Cyp11a1 mRNA expressions in a dose-dependent manner in MA-10 Leydig cells as demonstrated by transfection of a luciferase reporter plasmid. These results led to a significant increase in progesterone production from MA-10 cells. Thus, our data suggest that high doses of adiponectin typical of normal body weight may promote testosterone production from Leydig cells.

Changes in Serum Adiponectin in Mice Chronically Exposed to Inorganic Arsenic in Drinking Water.

PubMed

Song, Xuanbo; Li, Ying; Liu, Junqiu; Ji, Xiaohong; Zhao, Lijun; Wei, Yudan

2017-09-01

Cardiovascular disease and diabetes mellitus are prominent features of glucose and lipid metabolism disorders. Adiponectin is a key adipokine that is largely involved in glucose and lipid metabolism processes. A growing body of evidence suggests that chronic exposure to inorganic arsenic is associated with cardiovascular disease and diabetes mellitus. We hypothesized that arsenic exposure may increase the risk of cardiovascular disease and diabetes mellitus by affecting the level of adiponectin. In this study, we examined serum adiponectin levels, as well as serum levels of metabolic measures (including fasting blood glucose, insulin, total cholesterol, triglyceride, and high-density lipoprotein (HDL)-cholesterol) in C57BL/6 mice exposed to inorganic arsenic in drinking water (5 and 50 ppm NaAsO 2 ) for 18 weeks. Body mass and adiposity were monitored throughout the study. We found no significant changes in serum insulin and glucose levels in mice treated with arsenic for 18 weeks. However, arsenic exposure decreased serum levels of adiponectin, triglyceride, and HDL-cholesterol. Further, an inverse relationship was observed between urinary concentrations of total arsenic and serum levels of adiponectin. This study suggests that arsenic exposure could disturb the metabolism of lipids and increase the risk of cardiovascular disease by reducing the level of adiponectin.

High Serum Adiponectin Level Is a Risk Factor for Anemia in Japanese Men: A Prospective Observational Study of 1,029 Japanese Subjects

PubMed Central

Kohno, Kei; Narimatsu, Hiroto; Shiono, Yosuke; Suzuki, Ikuko; Kato, Yuichi; Sho, Ri; Otani, Katsumi; Ishizawa, Kenichi; Yamashita, Hidetoshi; Kubota, Isao; Ueno, Yoshiyuki; Kato, Takeo; Fukao, Akira; Kayama, Takamasa

2016-01-01

Erythroid abnormalities including anemia and polycythemia are often observed in the general clinical setting. Because recent studies reported that adiponectin negatively affects hematopoiesis, we performed a prospective observational study to assess the relationship between anemia and adiponectin, as well as other parameters, in 1029 Japanese subjects (477 men and 552 women) 40 years of age and older. Body measurements, blood tests, and nutrition intake studies were performed at baseline, and 5 to 7 years later (follow-up). Hemoglobin (Hb) and hematocrit (Hct) levels in men with high serum adiponectin levels were lower at follow-up than at baseline. Multiple regression analysis showed that age, body mass index, adiponectin, and glutamic-pyruvic transaminase were significantly associated with erythroid-related variables (red blood cells, Hb, and Hct) in both men and women (P <0.05). In a logistic regression analysis, adiponectin, fasting blood glucose, and β-natriuretic peptide were significant risk factors for anemia in men, and blood urea nitrogen and amylase were significant risk factors in women. Physical features and nutrient intake were not risk factors for anemia. Our study demonstrates, both clinically and epidemiologically, that a high serum adiponectin level decreases the amounts of erythroid-related variables and is a risk factor for anemia in Japanese men. PMID:27918575

The Effect of Omega-3 on Circulating Adiponectin in Adults with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Bahreini, Mehdi; Ramezani, Amir-Hossein; Shishehbor, Farideh; Mansoori, Anahita

2018-01-04

Whether consumption of omega-3 affects circulating adiponectin has not been established. The objective of this study was to evaluate the effect of omega-3 (food or supplement) on circulating adiponectin in patients with type 2 diabetes through a systematic review of meta-analyses of randomized controlled trials. PubMed, Scopus and Web of Science were searched for relevant studies through May 2016. Two researchers screened and abstracted the literature independently. Pooled estimates were obtained using the random-effects models. Overall, omega-3 increased adiponectin by 0.57 µg/mL (95% confidence interval [CI] 0.15 to 1.31; p=0.01, I-square=74.2% p for heterogeneity <0.001). The source of observed heterogeneity was explored by subgroup analyses. In subgroup analyses, adiponectin levels increased only in those who had consumed omega-3 for more than 8 weeks. This systematic review and meta-analysis of randomized, placebo-controlled clinical trials suggests that omega-3 in patients with type 2 diabetes increases circulating adiponectin. These findings support the potentially beneficial effects of dietary omega-3 in patients with type 2 diabetes on pathways related to adiponectin metabolism. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Adiponectin in eutrophic and obese children as a biomarker to predict metabolic syndrome and each of its components.

PubMed

Klünder-Klünder, Miguel; Flores-Huerta, Samuel; García-Macedo, Rebeca; Peralta-Romero, Jesús; Cruz, Miguel

2013-01-30

Obesity is associated with the rise of noncommunicable diseases worldwide. The pathophysiology behind this disease involves the increase of adipose tissue, being inversely related to adiponectin, but directly related to insulin resistance and metabolic syndrome (MetS). Therefore, this study aimed to determine the relationship between adiponectin levels with each component of MetS in eutrophic and obese Mexican children. A cross sectional study was conducted in 190 school-age children classified as obese and 196 classified as eutrophic. Adiponectin, glucose, insulin, high density lipoprotein cholesterol (HDL-C) and triglycerides were determined from a fasting blood sample. Height, weight, waist circumference, systolic and diastolic blood pressures (BP) were measured; MetS was evaluated with the IDF definition. The study groups were divided according to tertiles of adiponectin, using the higher concentration as a reference. Linear regression analysis was used to assess the association between adiponectin and components of the MetS. Finally, stepwise forward multiple logistic regression analysis controlling for age, gender, basal HOMA-IR values and BMI was performed to determine the odds ratio of developing MetS according to adiponectin tertiles. Anthropometric and metabolic measurements were statistically different between eutrophic and obese children with and without MetS (P <0.001). The prevalence of MetS in obese populations was 13%. Adiponectin concentrations were 15.5 ± 6.1, 12.0 ± 4.8, 12.4 ± 4.9 and 9.4 ± 2.8 μg/mL for eutrophic and obese subjects, obese without MetS, and obese with MetS, respectively (P <0.001). Obese children with low values of adiponectin exhibited a higher frequency of MetS components: abdominal obesity, 49%; high systolic BP, 3%; high diastolic BP, 2%; impaired fasting glucose, 17%; hypertriglyceridemia, 31%; and low HDL-C values, 42%. Adjusted odds ratio of presenting MetS according to adiponectin categories was 10.9 (95% CI 2.05; 48.16) when the first tertile was compared with the third. In this sample of eutrophic and obese Mexican children we found that adiponectin concentrations and MetS components have an inversely proportional relationship, which supports the idea that this hormone could be a biomarker for identifying individuals with risk of developing MetS.

Adiponectin in eutrophic and obese children as a biomarker to predict metabolic syndrome and each of its components

PubMed Central

2013-01-01

Background Obesity is associated with the rise of noncommunicable diseases worldwide. The pathophysiology behind this disease involves the increase of adipose tissue, being inversely related to adiponectin, but directly related to insulin resistance and metabolic syndrome (MetS). Therefore, this study aimed to determine the relationship between adiponectin levels with each component of MetS in eutrophic and obese Mexican children. Methods A cross sectional study was conducted in 190 school-age children classified as obese and 196 classified as eutrophic. Adiponectin, glucose, insulin, high density lipoprotein cholesterol (HDL-C) and triglycerides were determined from a fasting blood sample. Height, weight, waist circumference, systolic and diastolic blood pressures (BP) were measured; MetS was evaluated with the IDF definition. The study groups were divided according to tertiles of adiponectin, using the higher concentration as a reference. Linear regression analysis was used to assess the association between adiponectin and components of the MetS. Finally, stepwise forward multiple logistic regression analysis controlling for age, gender, basal HOMA-IR values and BMI was performed to determine the odds ratio of developing MetS according to adiponectin tertiles. Results Anthropometric and metabolic measurements were statistically different between eutrophic and obese children with and without MetS (P <0.001). The prevalence of MetS in obese populations was 13%. Adiponectin concentrations were 15.5 ± 6.1, 12.0 ± 4.8, 12.4 ± 4.9 and 9.4 ± 2.8 μg/mL for eutrophic and obese subjects, obese without MetS, and obese with MetS, respectively (P <0.001). Obese children with low values of adiponectin exhibited a higher frequency of MetS components: abdominal obesity, 49%; high systolic BP, 3%; high diastolic BP, 2%; impaired fasting glucose, 17%; hypertriglyceridemia, 31%; and low HDL-C values, 42%. Adjusted odds ratio of presenting MetS according to adiponectin categories was 10.9 (95% CI 2.05; 48.16) when the first tertile was compared with the third. Conclusion In this sample of eutrophic and obese Mexican children we found that adiponectin concentrations and MetS components have an inversely proportional relationship, which supports the idea that this hormone could be a biomarker for identifying individuals with risk of developing MetS. PMID:23363707

Effect of ethnicity, dietary intake and physical activity on plasma adiponectin concentrations among malaysian patients with type 2 diabetes mellitus.

PubMed

Chin, Koo Hui; Sathyasurya, Daniel Robert; Abu Saad, Hazizi; Jan Mohamed, Hamid Jan B

2013-01-01

The Malaysian Health and morbidity Survey (2006) reported the highest prevalence of type 2 diabetes mellitus (T2DM) among the Indian population compared to the Malay and Chinese populations. Many studies have supported the important role of adiponectin in insulin-sensitizing, which is associated with T2DM. These studies have raised a research question whether the variation in prevalence is related to the adiponectin concentrations or the lifestyle factors. The purpose of this study is to determine whether the adiponectin concentrations differ between the Malay, Chinese and the Indian populations with T2DM. It is to investigate the association of adiponectin concentrations with ethnicity, dietary intake and physical activity too. In this cross-sectional study, a total of 210 T2DM patients with mean (SD) age of 56.73 (10.23) years were recruited from Penang, Malaysia. Data on demographic background, medical history, anthropometry (weight, height, visceral fat, percentage of body fat and waist circumference), dietary intake (3 days 24 hours diet recall) and physical activity (International Physical Activity Questionnaire) were obtained accordingly. Plasma adiponectin and routine laboratory tests (fasting blood sugar, HbA1c, total cholesterol, LDL, HDL and triglyceride) were performed according to standard procedure. After adjustment for physical activity and dietary intakes, the Indian population had significantly lower adiponectin concentrations (P = 0.003) when compared with the Malay and the Chinese populations, The Indian population also had significantly higher value of HbA1c (P = 0.017) and significantly lower HDL (P = 0.013). Plasma adiponectin concentrations was significantly associated with ethnicity (P = 0.011), dietary carbohydrate (P = 0.003) and physical activity total MET score (P = 0.026), after medical history, age, sex, total cholesterol and visceral fat adjusted. However, dietary carbohydrate and physical activity did not show significantly difference among the various ethnic groups. In conclusion, lower concentration of adiponectin in the Indian population when compared with the Malay and the Chinese populations is not associated with lifestyle factors. The possibility of adiponectin gene polymorphism should be discussed further.

Filter Paper Blood Spot Enzyme Linked Immunoassay for Adiponectin and Application in the Evaluation of Determinants of Child Insulin Sensitivity

PubMed Central

Martin, Richard M.; Patel, Rita; Oken, Emily; Thompson, Jennifer; Zinovik, Alexander; Kramer, Michael S.; Vilchuck, Konstantin; Bogdanovich, Natalia; Sergeichick, Natalia; Foo, Ying; Gusina, Nina

2013-01-01

Background Adiponectin is an adipocyte-derived hormone that acts as a marker of insulin sensitivity. Bloodspot sampling by fingerstick onto filter paper may increase the feasibility of large-scale studies of the determinants of insulin sensitivity. We first describe the validation of an enzyme-linked immunoassay (ELISA) for quantifying adiponectin from dried blood spots and then demonstrate its application in a large trial (PROBIT). Methods We quantified adiponectin from 3-mm diameter discs (≈3 µL of blood) punched from dried blood spots obtained from: i) whole blood standards (validation); and ii) PROBIT trial samples (application) in which paediatricians collected blood spots from 13,879 children aged 11.5 years from 31 sites across Belarus. We examined the distribution of bloodspot adiponectin by demographic and anthropometric factors, fasting insulin and glucose. Results In the validation study, mean intra-assay coefficients of variation (n = 162) were 15%, 13% and 10% for ‘low’ (6.78 µg/ml), ‘medium’ (18.18 µg/ml) and 'high’ (33.13 µg/ml) internal quality control (IQC) samples, respectively; the respective inter-assay values (n = 40) were 23%, 21% and 14%. The correlation coefficient between 50 paired whole bloodspot versus plasma samples, collected simultaneously, was 0.87 (95% CI: 0.78 to 0.93). Recovery of known quantities of adiponectin (between 4.5 to 36 µg/ml) was 100.3–133%. Bloodspot adiponectin was stable for at least 30 months at −80°C. In PROBIT, we successfully quantified fasting adiponectin from dried blood spots in 13,329 of 13,879 (96%) children. Mean adiponectin (standard deviation) concentrations were 17.34 µg/ml (7.54) in boys and 18.41 µg/ml (7.92) in girls and were inversely associated with body mass index, fat mass, triceps and subscapular skin-fold thickness, waist circumference, height and fasting glucose. Conclusions Bloodspot ELISA is suitable for measuring adiponectin in very small volumes of blood collected on filter paper and can be applied to large-scale studies. PMID:23936498

Day/night variations of high-molecular-weight adiponectin and lipocalin-2 in healthy men studied under fed and fasted conditions.

PubMed

Scheer, F A J L; Chan, J L; Fargnoli, J; Chamberland, J; Arampatzi, K; Shea, S A; Blackburn, G L; Mantzoros, C S

2010-11-01

Adiponectin and lipocalin-2 are adipocyte-derived plasma proteins that have been proposed to have opposite effects on insulin sensitivity. Given the epidemiological, physiological and molecular links between sleep, the circadian timing system and glucose metabolism, the aim of this study was to assess effects of the sleep/wake cycle and the fasting/feeding cycle on high-molecular-weight adiponectin (HMW-adiponectin; the biologically active form) and lipocalin-2. We also aimed to compare the 24 h rhythms in the levels of these proteins with those of cortisol, leptin, leptin-binding protein and total adiponectin. Lean men underwent a 3 day in-laboratory study, either in the fed state (n = 8, age: 20.9 ± 2.1 years, BMI: 22.8 ± 2.3 kg/m²) or fasting state (3 day fast, n = 4, age: 25.3 ± 3.9 years, BMI: 23.3 ± 2.2 kg/m²). The sleep episode was scheduled in darkness from 23:00 to 07:00 hours. Blood was sampled every 15 min for 24 h on the third day of each study. While fed, HMW-adiponectin and lipocalin-2 had large daily rhythms with troughs at night (HMW-adiponectin: ~04:00 hours, peak-to-trough amplitude 36%, p < 0.0001; lipocalin-2: ~04:00 hours, 40%, p < 0.0001). On the third day of fasting, the timing and relative amplitudes were unchanged (HMW-adiponectin: ~04:00 hours, 38%, p = 0.0014; lipocalin-2: ~05:00 hours, 38%, p = 0.0043). These data show that HMW-adiponectin and lipocalin-2 both have significant day/night rhythms, both with troughs at night, that these are not driven by the feeding/fasting cycle, and that it is important to report and/or standardise the time of day for such assays. Further studies are required to determine whether the daily rhythm of HMW-adiponectin levels influences the daily rhythm of insulin sensitivity.

Effect of Ethnicity, Dietary Intake and Physical Activity on Plasma Adiponectin Concentrations Among Malaysian Patients with Type 2 Diabetes Mellitus

PubMed Central

Chin, Koo Hui; Sathyasurya, Daniel Robert; Abu Saad, Hazizi; Jan Mohamed, Hamid Jan B

2013-01-01

Background The Malaysian Health and morbidity Survey (2006) reported the highest prevalence of type 2 diabetes mellitus (T2DM) among the Indian population compared to the Malay and Chinese populations. Many studies have supported the important role of adiponectin in insulin-sensitizing, which is associated with T2DM. These studies have raised a research question whether the variation in prevalence is related to the adiponectin concentrations or the lifestyle factors. Objectives The purpose of this study is to determine whether the adiponectin concentrations differ between the Malay, Chinese and the Indian populations with T2DM. It is to investigate the association of adiponectin concentrations with ethnicity, dietary intake and physical activity too. Materials and Methods In this cross-sectional study, a total of 210 T2DM patients with mean (SD) age of 56.73 (10.23) years were recruited from Penang, Malaysia. Data on demographic background, medical history, anthropometry (weight, height, visceral fat, percentage of body fat and waist circumference), dietary intake (3 days 24 hours diet recall) and physical activity (International Physical Activity Questionnaire) were obtained accordingly. Plasma adiponectin and routine laboratory tests (fasting blood sugar, HbA1c, total cholesterol, LDL, HDL and triglyceride) were performed according to standard procedure. Results After adjustment for physical activity and dietary intakes, the Indian population had significantly lower adiponectin concentrations (P = 0.003) when compared with the Malay and the Chinese populations, The Indian population also had significantly higher value of HbA1c (P = 0.017) and significantly lower HDL (P = 0.013). Plasma adiponectin concentrations was significantly associated with ethnicity (P = 0.011), dietary carbohydrate (P = 0.003) and physical activity total MET score (P = 0.026), after medical history, age, sex, total cholesterol and visceral fat adjusted. However, dietary carbohydrate and physical activity did not show significantly difference among the various ethnic groups. Conclusions In conclusion, lower concentration of adiponectin in the Indian population when compared with the Malay and the Chinese populations is not associated with lifestyle factors. The possibility of adiponectin gene polymorphism should be discussed further. PMID:24348588

A pilot three-month sitagliptin treatment increases serum adiponectin level in Japanese patients with type 2 diabetes mellitus--a randomized controlled trial START-J study.

PubMed

Hibuse, Toshiyuki; Maeda, Norikazu; Kishida, Ken; Kimura, Takekazu; Minami, Tomoko; Takeshita, Eriko; Hirata, Ayumu; Nakagawa, Yasuhiko; Kashine, Susumu; Oka, Akemi; Hayashi, Masumi; Nishizawa, Hitoshi; Funahashi, Tohru; Shimomura, Iichiro

2014-05-24

The dipeptidyl-peptidase-IV (DPP-4) inhibitors, including sitagliptin, are used for the treatment of type 2 diabetes mellitus (T2DM). Adiponectin, an adipocyte-derived circulating protein, has anti-atherosclerotic and anti-diabetic properties and is effectively elevated in bloodstream by thiazolidinediones, an insulin sensitizer. However, the effect of sitagliptin treatment on serum adiponectin level in T2DM has not fully elucidated in Japanese T2DM patients. The aim of the present study was to examine the effect of sitagliptin treatment on serum adiponectin levels in T2DM subjects. Twenty-six consecutive Japanese T2DM outpatients were recruited between April 2011 and March 2013, and randomized into the control (conventional treatment, n = 10) group and sitagliptin treatment group (n = 16). Serum adiponectin was measured by enzyme-linked immunosorbent assay. Indices of glycemic control, such as hemoglobin A1c, glycated albumin, and 1.5-anhydro-D-glucitol, were significantly improved after the three-month treatment in both the control and sitagliptin groups. Serum adiponectin level was significantly increased in sitagliptin group from 6.7 ± 0.8 to 7.4 ± 1.0 μg/mL without change of body mass index (p = 0.034), while serum adiponectin level was not altered in the control group (p = 0.601). In Japanese T2DM patients, serum adiponectin level was elevated by three-month treatment with sitagliptin without change of body weight. UMIN000004721.

Adiponectin, Leptin, and Yoga Practice

PubMed Central

Kiecolt-Glaser, Janice K.; Christian, Lisa M.; Andridge, Rebecca; Hwang, Beom Seuk; Malarkey, William B.; Belury, Martha A.; Emery, Charles F.; Glaser, Ronald

2012-01-01

To address the mechanisms underlying hatha yoga’s potential stress-reduction benefits, we compared adiponectin and leptin data from well-matched novice and expert yoga practitioners. These adipocytokines have counter-regulatory functions in inflammation; leptin plays a proinflammatory role, while adiponectin has anti-inflammatory properties. Fifty healthy women (mean age=41.32, range=30-65), 25 novices and 25 experts, provided fasting blood samples during three separate visits. Leptin was 36% higher among novices compared to experts, P = .008. Analysis of adiponectin revealed a borderline effect of yoga expertise, P = .08; experts’ average adiponectin levels were 28% higher than novices across the three visits. In contrast, experts’ average adiponectin to leptin ratio was nearly twice that of novices, P = .009. Frequency of self-reported yoga practice showed significant negative relationships with leptin; more weeks of yoga practice over the last year, more lifetime yoga sessions, and more years of yoga practice were all significantly associated with lower leptin, with similar findings for the adiponectin to leptin ratio. Novices and experts did not show even marginal differences on behavioral and physiological dimensions that might represent potential confounds, including BMI, central adiposity, cardiorespiratory fitness, and diet. Prospective studies addressing increased risk for type II diabetes, hypertension, and cardiovascular disease have highlighted the importance of these adipocytokines in modulating inflammation. Although these health risks are clearly related to more extreme values then we found in our healthy sample, our data raise the possibility that longer-term and/or more intensive yoga practice could have beneficial health consequences by altering leptin and adiponectin production. PMID:22306535

Adiponectin as a Protective Factor Against the Progression Toward Type 2 Diabetes Mellitus in Postmenopausal Women.

PubMed

Darabi, Hossein; Raeisi, Alireza; Kalantarhormozi, Mohammad Reza; Ostovar, Afshin; Assadi, Majid; Asadipooya, Kamyar; Vahdat, Katayoun; Dobaradaran, Sina; Nabipour, Iraj

2015-08-01

Serum adiponectin levels have been suggested to be predictors of type 2 diabetes mellitus in diverse populations. However, the relationship between circulating adiponectin levels and the risk of development of type 2 diabetes in postmenopausal women has not been investigated.A total of 382 healthy postmenopausal women who participated in a prospective cohort study were followed for 5.8 years. Type 2 diabetes mellitus was defined according to the criteria set out by the American Diabetes Association. Adiponectin, osteoprotegerin (OPG), and high-sensitivity C-reactive protein (hs-CRP) levels were measured using ELISA.Of 195 women who did not have diabetes at baseline and who were reexamined in the second phase of the study for diabetic status, 35 subjects (17.9%) developed type 2 diabetes mellitus during the 5.8 years follow-up period. The women with type 2 diabetes had lower adiponectin levels than the healthy postmenopausal women. Multiple regression analysis showed that, after adjustments were made for age, cardiovascular risk factors, OPG, and hs-CRP levels, higher baseline adiponectin levels were associated with a lower relative risk (RR) of having type 2 (RR = 0.07, confidence interval [CI]: 0.01-0.66, P = 0.021).Higher baseline adiponectin levels functioned as a predictor of a lower risk of developing type 2 diabetes mellitus among postmenopausal women during a 5.8 years follow-up study. Therefore, it is suggested that elevated adiponectin levels may offer protection against the development of type 2 diabetes mellitus after the menopause.

Associations of adiponectin and leptin with stage and grade of PSA-detected prostate cancer: the ProtecT study.

PubMed

Burton, Anya; Martin, Richard M; Holly, Jeff; Lane, J Athene; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Tilling, Kate

2013-02-01

Obesity has been associated with an increased risk of advanced and fatal prostate cancer; adipokines may mediate this association. We examined associations of the adipokines leptin and adiponectin with the stage and grade of PSA-detected prostate cancer. We conducted a nested case-control study comparing 311 men with mainly locally advanced (≥T3, N1, or M1 cases) vs. 413 men with localized (T ≤2 & NX-0 & M0 controls) PSA-detected prostate cancer, recruited 2001-2009 from 9 UK regions to the ProtecT study. Associations of body mass index and adipokine levels with prostate cancer stage were determined by conditional logistic regression and with grade (Gleason score ≥7 vs. ≤6) by unconditional logistic regression. Adiponectin was inversely associated with prostate cancer stage in overweight and obese men (OR 0.62; 95 % CI 0.42-0.90; p = 0.01), but not in normal weight men (OR 1.48; 0.77-2.82; p = 0.24) (p for interaction 0.007), or all men (OR 0.86; 0.66-1.11; p = 0.24). There was no compelling evidence of associations between leptin or leptin to adiponectin ratio and prostate cancer stage. No strong associations of adiponectin, leptin, or leptin:adiponectin ratio with grade were seen. This study provides some evidence that adiponectin levels may be associated with prostate cancer stage, dependent on the degree of adiposity of the man. Our results are consistent with adiponectin countering the adverse effects of obesity on prostate cancer progression.

Carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults in the Framingham Offspring Cohort

USDA-ARS?s Scientific Manuscript database

Diet may influence circulating adiponectin levels by improving insulin sensitivity. We examined the associations between carbohydrate-related dietary factors and plasma adiponectin levels in healthy adults aged 26–81 y (n= 979 men and 1227 women). Dietary intakes were assessed using a FFQ. Fasting...

Globular domain of adiponectin: promising target molecule for detection of atherosclerotic lesions

PubMed Central

Almer, Gunter; Saba-Lepek, Matthias; Haj-Yahya, Samih; Rohde, Eva; Strunk, Dirk; Fröhlich, Eleonore; Prassl, Ruth; Mangge, Harald

2011-01-01

Background: Adiponectin, an adipocyte-specific plasma protein, has been shown to accumulate in injured endothelial cells during development of atherosclerotic lesions. In this study, we investigated the potential of different adiponectin subfractions with special emphasis on globular adiponectin (gAd) to recognize and visualize atherosclerotic lesions. Methods: Recombinant mouse gAd and subfractions of full-length adiponectin (ie, trimeric, hexameric, and oligomeric forms) were fluorescence-labeled. Aortas of wild-type and apoprotein E-deficient mice fed a high cholesterol diet were dissected and incubated with the labeled biomarkers. Imaging was performed using confocal laser scanning microscopy. Results: Confocal laser scanning microscopic images showed that gAd binds more strongly to atherosclerotic plaques than full-length adiponectin subfractions. Further, we showed that gAd accumulates preferentially in endothelial cells and the fibrous cap area of plaques. Here we demonstrate for the first time that gAd recognizes atherosclerotic plaques on aortic sections of apoprotein E-deficient mice. Conclusion: These results suggest that gAd, in addition to its physiological properties, is also suitable as a target molecule for prospective diagnostic strategies in imaging atherosclerotic lesions. PMID:22022204

An FGF21-adiponectin-ceramide axis controls energy expenditure and insulin action in mice.

PubMed

Holland, William L; Adams, Andrew C; Brozinick, Joseph T; Bui, Hai H; Miyauchi, Yukiko; Kusminski, Christine M; Bauer, Steven M; Wade, Mark; Singhal, Esha; Cheng, Christine C; Volk, Katherine; Kuo, Ming-Shang; Gordillo, Ruth; Kharitonenkov, Alexei; Scherer, Philipp E

2013-05-07

FGF21, a member of the fibroblast growth factor (FGF) superfamily, has recently emerged as a regulator of metabolism and energy utilization. However, the exact mechanism(s) whereby FGF21 mediates its actions have not been elucidated. There is considerable evidence that insulin resistance may arise from aberrant accumulation of intracellular lipids in insulin-responsive tissues due to lipotoxicity. In particular, the sphingolipid ceramide has been implicated in this process. Here, we show that FGF21 rapidly and robustly stimulates adiponectin secretion in rodents while diminishing accumulation of ceramides in obese animals. Importantly, adiponectin-knockout mice are refractory to changes in energy expenditure and ceramide-lowering effects evoked by FGF21 administration. Moreover, FGF21 lowers blood glucose levels and enhances insulin sensitivity in diabetic Lep(ob/ob) mice and diet-induced obese (DIO) mice only when adiponectin is functionally present. Collectively, these data suggest that FGF21 is a potent regulator of adiponectin secretion and that FGF21 critically depends on adiponectin to exert its glycemic and insulin sensitizing effects. Copyright © 2013 Elsevier Inc. All rights reserved.

Validation of 2 commercially available enzyme-linked immunosorbent assays for adiponectin determination in canine serum samples.

PubMed

Tvarijonaviciute, Asta; Martínez-Subiela, Silvia; Ceron, José J

2010-10-01

The aim of this study was to validate 2 commercially available enzyme-linked immunosorbent assays (ELISAs) for adiponectin in dogs, 1 canine-specific and 1 originally designed for measurements in humans. Intra-assay and interassay precision was evaluated by multiple measurements in canine serum samples, and assay accuracy was indirectly determined by linearity under dilution. Interference caused by hemolysis and lipemia was also studied. Both assays were subsequently used for measuring adiponectin concentrations in clinically healthy dogs and those with different grades of obesity. The intra-assay and inter-assay precision was less than 7.5% and 13.5% in serum samples with low and high adiponectin concentrations, respectively. Lipemia and hemolysis did not affect the results of any of the assays. Both assays were able to differentiate lean dogs from those that were overweight or obese on the basis of the measured adiponectin concentrations. From these results it can be concluded that canine adiponectin concentrations can be measured reliably by means of the 2 ELISAs evaluated in this study.

Validation of 2 commercially available enzyme-linked immunosorbent assays for adiponectin determination in canine serum samples

PubMed Central

Tvarijonaviciute, Asta; Martínez-Subiela, Silvia; Ceron, José J.

2010-01-01

The aim of this study was to validate 2 commercially available enzyme-linked immunosorbent assays (ELISAs) for adiponectin in dogs, 1 canine-specific and 1 originally designed for measurements in humans. Intra-assay and interassay precision was evaluated by multiple measurements in canine serum samples, and assay accuracy was indirectly determined by linearity under dilution. Interference caused by hemolysis and lipemia was also studied. Both assays were subsequently used for measuring adiponectin concentrations in clinically healthy dogs and those with different grades of obesity. The intra-assay and inter-assay precision was less than 7.5% and 13.5% in serum samples with low and high adiponectin concentrations, respectively. Lipemia and hemolysis did not affect the results of any of the assays. Both assays were able to differentiate lean dogs from those that were overweight or obese on the basis of the measured adiponectin concentrations. From these results it can be concluded that canine adiponectin concentrations can be measured reliably by means of the 2 ELISAs evaluated in this study. PMID:21197228

Fat-cell mass, serum leptin and adiponectin changes during weight gain and loss in yellow-bellied marmots (Marmota flaviventris).

PubMed

Florant, Gregory L; Porst, Heather; Peiffer, Aubrey; Hudachek, Susan F; Pittman, Chris; Summers, Scott A; Rajala, Michael W; Scherer, Philipp E

2004-11-01

Leptin and adiponectin are proteins produced and secreted from white adipose tissue and are important regulators of energy balance and insulin sensitivity. Seasonal changes in leptin and adiponectin have not been investigated in mammalian hibernators in relationship to changes in fat cell and fat mass. We sought to determine the relationship between serum leptin and adiponectin levels with seasonal changes in lipid mass. We collected serum and tissue samples from marmots (Marmota flaviventris) in different seasons while measuring changes in fat mass, including fat-cell size. We found that leptin is positively associated with increasing fat mass and fat-cell size, while adiponectin is negatively associated with increasing lipid mass. These findings are consistent with the putative roles of these adipokines: leptin increases with fat mass and is involved in enhancing lipid oxidation while adiponectin appears to be higher in summer when hepatic insulin sensitivity should be maintained since the animals are eating. Our data suggest that during autumn/winter animals have switched from a lipogenic condition to a lipolytic state, which may include leptin resistance.

γ-Oryzanol recovers mouse hypoadiponectinemia induced by animal fat ingestion.

PubMed

Nagasaka, Reiko; Yamsaki, Tomoteru; Uchida, Asako; Ohara, Kazuyuki; Ushio, Hideki

2011-06-15

Adiponectin is an insulin-sensitizing adipocyte-derived adipokine. The decrease in plasma adiponectin level (hypoadiponectinemia) is involved in the development of insulin resistance and the resulting type 2 diabetes. Our previous studies have demonstrated that γ-oryzanol (ORZ) from rice bran suppressed NF-κB activation and increased adiponectin secretion from adipocyte. In this study, we have evaluated effects of oral administration of animal fat (beef tallow) and palmitate on mouse serum adiponectin level. Oral administrations of beef tallow and palmitate significantly suppressed serum adiponectin levels into around half of the initial level from 48 to 96 h after administration compared with the case of corn oil (P<0.05). Coadministration of ORZ successfully remedied mouse hypoadiponectinemia induced by ingestion of beef tallow and the relative adiponectin levels attained to 1.66±0.23 at 96 h after administration (mean value±s.e., P<0.05). Diverse physiological functions of ORZ in crop bran might be promising us to prevent chronic inflammations in the pathogeneses of the metabolic or insulin resistance syndromes. Copyright © 2011 Elsevier GmbH. All rights reserved.

Reduced high-molecular-weight adiponectin and elevated high-sensitivity C-reactive protein are synergistic risk factors for metabolic syndrome in a large-scale middle-aged to elderly population: the Shimanami Health Promoting Program Study.

PubMed

Tabara, Yasuharu; Osawa, Haruhiko; Kawamoto, Ryuichi; Tachibana-Iimori, Rieko; Yamamoto, Miyuki; Nakura, Jun; Miki, Tetsuro; Makino, Hideich; Kohara, Katsuhiko

2008-03-01

In Western countries, one of the most important modifiable targets for the prevention of cardiovascular diseases is metabolic syndrome. Adiponectin is an adipose tissue-specific plasma protein that inversely associates with metabolic syndrome. Among several molecular isoforms, high-molecular-weight (HMW) complex is considered the active form. Increased serum high-sensitivity C-reactive protein (hsCRP) concentration also associates with metabolic syndrome, and adiponectin could modulate plasma C-reactive protein levels. Here, through cross-sectional investigation, we investigated whether reduced HMW adiponectin and increased hsCRP levels in plasma are synergistically associated with metabolic syndrome. Measurement of HMW complex of adiponectin is one of the novelties of this study. We analyzed 1845 community-dwelling middle-aged to elderly subjects (62+/-13 yr). Plasma HMW adiponectin levels were measured by ELISA. Clinical parameters were obtained from the subjects' personal health records, evaluated at their annual medical check-up. Each component of metabolic syndrome, except for raised blood pressure, showed significantly lower plasma HMW adiponectin concentrations for both men and women (P<0.001). In contrast, plasma hsCRP levels were significantly higher in subjects with metabolic disorders (P<0.001). After adjusting for other confounding factors, HMW adiponectin [log normalized, odds ratio 0.084 (95% confidence interval 0.050-0.142), P<0.001] and hsCRP [3.009 (2.175-4.163), P<0.001] were identified as independent determinants of metabolic syndrome. In addition to the direct associations, we also observed a synergistic effect between these two molecules (F=11.8, P<0.001). Reduced HMW adiponectin and elevated hsCRP are synergistically associated with the accumulation of metabolic disorders. The combination of these markers would be useful for identifying at-risk populations.

Role of genetic variants in ADIPOQ in human eating behavior.

PubMed

Rohde, Kerstin; Keller, Maria; Horstmann, Annette; Liu, Xuanshi; Eichelmann, Fabian; Stumvoll, Michael; Villringer, Arno; Kovacs, Peter; Tönjes, Anke; Böttcher, Yvonne

2015-01-01

The beneficial effects of adiponectin and its negative correlation with BMI are well described. Adiponectin serum levels are altered in eating disorders such as anorexia nervosa, bulimia nervosa or binge eating. Here, we tested the hypothesis that (1) adiponectin serum levels correlate with human eating behavior factors and (2) that genetic variants of the ADIPOQ locus influence both serum levels and eating behavior. We analyzed 11 SNPs within ADIPOQ and in the 5' UTR and measured serum adiponectin levels in 1,036 individuals from the German Sorbs population. The German version of the three-factor eating questionnaire (FEV) was completed by 548 Sorbs. For replication purposes, we included an independent replication cohort from Germany (N = 350). In the Sorbs, we observed positive correlations of restraint with adiponectin serum levels (P = 0.001; r = 0.148) which, however, did not withstand adjustment for covariates (P = 0.083; r = 0.077). In addition, four SNPs were nominally associated with serum adiponectin levels (all P < 0.05). Of these, two variants (rs3774261; rs1501229, all P < 0.05) were also related to disinhibition. Furthermore, three variants were exclusively associated with hunger (rs2036373, P = 0.049) and disinhibition (rs822396; rs864265, all P < 0.05). However, none of these associations withstood Bonferroni corrections for multiple testing (all P > 9.3 × 10(-4)). In our replication cohort, we observed similar effect directions at rs1501229 for disinhibition and hunger. A meta-analysis resulted in nominal statistical significance P = 0.036 (Z score 2.086) and P = 0.017 (Z score 2.366), respectively. Given the observed relationship of the SNPs with adiponectin levels and eating behavior, our data support a potential role of adiponectin in human eating behavior. Whether the relationship with eating behavior is mediated by the effects of circulating adiponectin warrants further investigations.

Impact of the Adipokine Adiponectin and the Hepatokine Fetuin-A on the Development of Type 2 Diabetes: Prospective Cohort- and Cross-Sectional Phenotyping Studies

PubMed Central

Stefan, Norbert; Sun, Qi; Fritsche, Andreas; Machann, Jürgen; Schick, Fritz; Gerst, Felicia; Jeppesen, Charlotte; Joost, Hans-Georg; Hu, Frank B.; Boeing, Heiner; Ullrich, Susanne; Häring, Hans-Ulrich; Schulze, Matthias B.

2014-01-01

Background Among adipokines and hepatokines, adiponectin and fetuin-A were consistently found to predict the incidence of type 2 diabetes, both by regulating insulin sensitivity. Objective To determine to what extent circulating adiponectin and fetuin-A are independently associated with incident type 2 diabetes in humans, and the major mechanisms involved. Methods Relationships with incident diabetes were tested in two cohort studies: within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study (628 cases) and the Nurses' Health Study (NHS; 470 cases). Relationships with body fat compartments, insulin sensitivity and insulin secretion were studied in the Tübingen Lifestyle Intervention Program (TULIP; N = 358). Results Circulating adiponectin and fetuin-A, independently of several confounders and of each other, associated with risk of diabetes in EPIC-Potsdam (RR for 1 SD: adiponectin: 0.45 [95% CI 0.37–0.54], fetuin-A: 1.18 [1.05–1.32]) and the NHS (0.51 [0.42–0.62], 1.35 [1.16–1.58]). Obesity measures considerably attenuated the association of adiponectin, but not of fetuin-A. Subjects with low adiponectin and concomitantly high fetuin-A had the highest risk. Whereas both proteins were independently (both p<1.8×10−7) associated with insulin sensitivity, circulating fetuin-A (r = −0.37, p = 0.0004), but not adiponectin, associated with insulin secretion in subjects with impaired glucose tolerance. Conclusions We provide novel information that adiponectin and fetuin-A independently of each other associate with the diabetes risk. Furthermore, we suggest that they are involved in the development of type 2 diabetes via different mechanisms, possibly by mediating effects of their source tissues, expanded adipose tissue and nonalcoholic fatty liver. PMID:24643166

Adiponectin is not associated with renal function decline in community-dwelling elderly adults.

PubMed

Kobayashi, Hiroki; Otsuka, Hiromasa; Yanai, Mitsuru; Haketa, Akira; Hara, Motohiko; Hishiki, Mikano; Abe, Masanori; Soma, Masayoshi

2018-05-01

Adiponectin secreted by adipocytes plays an important role in the regulation of glucose and fatty acid metabolism. Contrary to findings in patients with chronic kidney disease (CKD), no prospective data about the association of serum adiponectin with renal function decline in the general population have yet appeared. Our objective was to analyze the relationship of total and high molecular weight (HMW) adiponectin with renal function decline as measured by cystatin C in community-dwelling elderly adults without moderate or severe CKD.In a prospective observational analysis, a total of 216 healthy elderly volunteers with eGFRcys ≥60 mL/min/1.73 m underwent anthropometric and laboratory tests at baseline and at follow-up visits. A subgroup with serum samples collected 5 years apart was further analyzed.There were no differences in either total or HMW adiponectin level between subjects subsequently undergoing rapid renal function decline and subjects with normal physiologic renal function decline (P = .71, P = .81). On univariate linear regression, neither total nor HMW adiponectin were associated with annual renal function decline (β = -0.23; P = .71, β = -0.057; P = .90). Multivariate analysis did not show a significant contribution of either total or HMW adiponectin to annual renal function decline (β = -0.50; P = .46, β = 0.01; P = .98). In the logistic regression analysis, we did not observe any statistically significant association of serum adiponectin levels with rapid renal function decline or incidence of CKD.Contrary to findings in populations with CKD, neither total nor HMW adiponectin had a substantial association with renal function decline in an elderly population with eGFRcys ≥60 mL/min/1.73 m. Our results and conclusions should not be extrapolated to subjects with other characteristics.

Nitric Oxide Bioavailability and Adiponectin Production in Chronic Systolic Heart Failure: Relation to Severity of Cardiac Dysfunction

PubMed Central

Tang, W.H. Wilson; Shrestha, Kevin; Tong, Wilson; Wang, Zeneng; Troughton, Richard W.; Borowski, Allen G.; Klein, Allan L.; Hazen, Stanley L.

2013-01-01

Adiponectin is an anti-inflammatory, anti-atherogenic adipokine elevated in heart failure (HF) that may protect against endothelial dysfunction by influencing underlying nitric oxide bioavailablity. In this study, we examine the relationship between plasma adiponectin levels and measures of nitric oxide bioavailability and myocardial performance in patients with chronic systolic HF. In 139 ambulatory patients with stable, chronic systolic HF (left ventricular [LV] ejection fraction ≤40%, New York Heart Association [NYHA] class I to IV), we measured plasma levels of adiponectin, asymmetric dimethylarginine (ADMA) and global arginine bioavailability (GABR), and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse events (all-cause mortality or cardiac transplantation) were prospectively tracked for a median of 39 months. Plasma adiponectin levels directly correlated with plasma ADMA levels (Spearman’s r=0.41, p<0.001) and NT-proBNP levels (r=0.55, p<0.001), inversely correlated with GABR (r= −0.39, p<0.001), and were not associated with hsCRP (p=0.81) or MPO (p=0.07). Interestingly, increased plasma adiponectin levels remained positively correlated with plasma ADMA levels only in patients with elevated NT-proBNP levels (r= 0.33, p=0.009). Higher plasma adiponectin levels were associated with worse LV diastolic dysfunction (rank sums p=0.002), RV systolic dysfunction (rank sums p=0.002), and RV diastolic dysfunction (rank sums p=0.011), but not after adjustment for plasma ADMA and NT-proBNP levels. Plasma adiponectin levels predicted increased risk of adverse clinical events (HR [95% CI]: 1.45 [1.02–2.07], p=0.038) but not after adjustment for plasma ADMA and NT-proBNP levels, or echocardiographic indices of diastolic or RV systolic dysfunction. In patients with chronic systolic HF, adiponectin production is more closely linked with nitric oxide bioavailability than inflammation, and appears to be more robust in the setting of cardiac dysfunction or elevated natriuretic peptide levels. PMID:23499315

The effect of multimeric adiponectin isoforms and leptin on the function of rheumatoid fibroblast-like synoviocytes.

PubMed

Kontny, E; Janicka, I; Skalska, U; Maśliński, W

2015-01-01

To evaluate the effects of physiologically relevant concentrations of multimeric adiponectin isoforms and leptin on the function of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). FLS, isolated from the synovial tissue of 21 RA patients, were stimulated for 24 h with interleukin (IL)-1β (1 ng/mL) and adiponectin isoforms [fraction enriched with high-molecular-weight (HMW) oligomers and middle-molecular-weight (MMW) hexamers or low-molecular-weight (LMW) trimers, 10 μg/mL each], or leptin (10 ng/mL), either separately or in a combination of IL-1β and the respective adipokine. Moreover, cells were pre-treated for 24 h with adipokines, then stimulated for 8 h with IL-1β. The concentrations of IL-6, IL-8, matrix metalloproteinase (MMP)-3, and dickkopf (DKK)-1, an inhibitor of osteoblastogenesis, in culture supernatants, as well as the concentrations of leptin, HMW, MMW, and LMW adiponectin in sera and synovial fluid (SF) samples, were measured by specific enzyme-linked immunosorbent assays (ELISAs). In comparison with sera, SF samples contained similar amounts of leptin, lower amounts of total adiponectin but a higher proportion of the LMW isoform. Separately added IL-1β and HMW/MMW adiponectin, but not LMW adiponectin or leptin, up-regulated the release of IL-6, IL-8, and MMP-3 from FLS but no synergy was observed in co-stimulation experiments. However, pre-treatment of FLS with HMW/MMW or LMW significantly raised the IL-1β-triggered secretion of MMP-3 and IL-6 or MMP-3, respectively. Adiponectin not only triggers pro-inflammatory and pro-destructive activities of rheumatoid FLS but also pre-disposes these cells to a stronger response to IL-1β. Thus, it is likely that adiponectin is more important in the initiation phase than in the chronic phase of RA.

Adiponectin activation of AMPK disrupts leptin-mediated hepatic fibrosis via suppressors of cytokine signaling (SOCS-3).

PubMed

Handy, Jeffrey A; Saxena, Neeraj K; Fu, Pingping; Lin, Songbai; Mells, Jamie E; Gupta, Nitika A; Anania, Frank A

2010-08-01

Adiponectin is an adipocytokine that was recently shown to be anti-fibrogenic in hepatic fibrosis. Leptin, on the other hand, promotes hepatic fibrosis. The purpose of the present study was to elucidate a mechanism (or mechanisms) whereby adiponectin dampens leptin signaling in activated hepatic stellate cells (HSCs), and prevents excess extracellular matrix production. Activated HSCs, between passages 2 and 5, were cultured and exposed to recombinant human adiponectin and recombinant leptin. Immunoblot analysis for SOCS-3, TIMP-1, and the phosphorylated species of Stat3 and adenosine monophosphate-activated protein kinase (AMPK) were conducted. We also examined MMP-1 activity by immunosorbant fluorimetric analysis. In HSCs, adiponectin-induced phosphorylation of AMPK, and subsequently suppressed leptin-mediated Stat3 phosphorylation and SOCS-3 induction. Adiponectin also blocked leptin-stimulated secretion of TIMP-1, and significantly increased MMP-1 activity, in vitro. To extend this study, we treated adiponectin knockout mice (Ad-/-) daily with 5 mg/kg recombinant leptin and/or carbon tetrachloride (2 ml/kg) for 6 weeks. Post-necropsy analysis was performed to examine for inflammation, and histological changes in the Ad-/- and wild-type mice. There was no significant difference in inflammation, or aminotransferases, between mice receiving carbon tetrachloride and leptin versus carbon tetrachloride alone. As anticipated, the combination of leptin and CCl(4) enhanced hepatic fibrosis in both wild-type and Ad-/- mice, as estimated by amount of collagen in injured livers, but wild-type mice had significantly higher levels of SOCS-3 and significantly lower levels of TIMP-1 mRNA and protein than did adiponectin KO mice exposed to both CCl(4) and leptin. We therefore conclude that the protective effects of adiponectin against liver fibrosis require AMPK activation, and may occur through inhibition of the Jak-Stat signal transduction pathway. Published 2010 Wiley-Liss, Inc.

Single nucleotide polymorphisms at the ADIPOQ gene locus interact with age and dietary intake of fat to determine serum adiponectin in subjects at risk of the metabolic syndrome1234

PubMed Central

AlSaleh, Aseel; O'Dell, Sandra D; Frost, Gary S; Griffin, Bruce A; Lovegrove, Julie A; Jebb, Susan A; Sanders, Thomas AB

2011-01-01

Background: Adiponectin gene expression is modulated by peroxisome proliferator–activated receptor γ, which is a transcription factor activated by unsaturated fatty acids. Objective: We investigated the effect of the interaction between variants at the ADIPOQ gene locus, age, sex, body mass index (BMI), ethnicity, and the replacement of dietary saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) or carbohydrates on serum adiponectin concentrations. Design: The RISCK (Reading, Imperial, Surrey, Cambridge, and Kings) study is a parallel-design, randomized controlled trial. Serum adiponectin concentrations were measured after a 4-wk high-SFA (HS) diet and a 24-wk intervention with reference (HS), high-MUFA (HM), and low-fat (LF) diets. Single nucleotide polymorphisms at the ADIPOQ locus −11391 G/A (rs17300539), −10066 G/A (rs182052), −7734 A/C (rs16861209), and +276 G/T (rs1501299) were genotyped in 448 participants. Results: In white Europeans, +276 T was associated with higher serum adiponectin concentrations (n = 340; P = 0.006) and −10066 A was associated with lower serum adiponectin concentrations (n = 360; P = 0.03), after adjustment for age, BMI, and sex. After the HM diet, −10066 G/G subjects showed a 3.8% increase (95% CI: −0.1%, 7.7%) and G/A+A/A subjects a 2.6% decrease (95% CI: −5.6%, 0.4%) in serum adiponectin (P = 0.006 for difference after adjustment for the change in BMI, age, and sex). In −10066 G/G homozygotes, serum adiponectin increased with age after the HM diet and decreased after the LF diet. Conclusion: In white −10066 G/G homozygotes, an HM diet may help to increase adiponectin concentrations with advancing age. This trial was registered at clinicaltrials.gov as ISRCTN29111298. PMID:21562092

Association between serum adiponectin levels and muscular fitness in Portuguese adolescents: LabMed Physical Activity Study.

PubMed

Agostinis-Sobrinho, C; Santos, R; Moreira, C; Abreu, S; Lopes, L; Oliveira-Santos, J; Rosário, R; Póvoas, S; Mota, J

2016-06-01

Paradoxically, recent investigations have showed that adiponectin levels are inversely associated with muscle strength. However, to date, there is a lack of knowledge on the relationship between muscular fitness (MF) and adiponectin levels in adolescents. We aimed to examine the independent associations between MF and adiponectin levels in adolescents, controlling for several potential confounders. This is a cross-sectional analysis with 529 Portuguese adolescents aged 12-18 years. A MF score was computed as the mean of the handgrip strength and standing long jump standardized values by age and gender. We measured fasting glucose, insulin, HDL-cholesterol, C-reactive protein and adiponectin. Linear regression analysis showed a significant inverse association between adiponectin (Z-score by age and sex) and MF score, after adjustments for age, sex, pubertal stage, socioeconomic status, adherence to the Mediterranean diet, body mass index, HOMA-IR, HDL-cholesterol, C-reactive protein and cardiorespiratory fitness (unstandardized β = -0.176; p < 0.005). Analysis of covariance showed a significant difference between the Low MF/Non-overweight group and the High MF/Non-overweight Group (p < 0.05) and between the Low MF/Non-overweight and High MF/Overweight Group (p < 0.05) (F (5, 523) = 2.262, p = 0.047). Adiponectin circulating levels are inversely and independently associated with MF. In non-overweight adolescents, those with high levels of MF presented lower levels of adiponectin compared to those with Low MF. Likewise, overweight adolescents with High MF presented lower levels of serum adiponectin than non-overweight adolescents with Low MF. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

The relationship between serum adiponectin and postpartum luteal activity in high-producing dairy cows.

PubMed

Kafi, Mojtaba; Tamadon, Amin; Saeb, Mehdi

2015-05-01

The aims of the present study were to initially determine the pattern of serum adiponectin concentrations during a normal estrous cycle in high-producing postpartum dairy cows and then evaluate the relationship between the serum concentrations of adiponectin and insulin with the commencement of postpartum luteal activity and ovarian activities in clinically healthy high-producing Holstein dairy cows. During a normal estrous cycle of cows (n = 6), serum adiponectin concentrations gradually decreased (P < 0.05) after ovulation by Day-17 estrous cycle and then increased before the next ovulation. Cows with higher peak of milk yield had lower serum adiponectin concentrations by week 7 postpartum (P = 0.01). Serum adiponectin and insulin concentrations in cows with different postpartum luteal activity (based on the progesterone profile) were evaluated using the following class of cows: normal (≤45 days, n = 11) and delayed (>45 days, n = 11) commencement of luteal activity (C-LA) and four different profiles of normal luteal activity (NLA, n = 5), prolonged luteal phase (n = 6), delayed first ovulation (n = 6), and anovulation (AOV, n = 5). Serum adiponectin concentrations decreased gradually by week 3 postpartum in NLA and then increased; whereas in AOV and delayed first ovulation, they were decreased after week 3 postpartum (P < 0.05). Moreover, serum adiponectin concentrations in NLA were more than AOV at weeks 5 and 7 postpartum (P = 0.05). The increase in the milk yield from weeks 1 to 7 postpartum in prolonged luteal phase (P = 0.05) and AOV (P = 0.04) cows was more than that of NLA cows. Insulin concentrations were almost maintained at a stable level in NLA cows (P > 0.05), whereas they increased in the other groups (P < 0.05). Moreover, adiponectin concentrations in cows with C-LA greater than 45 days decreased more than those with C-LA 45 days or less after week 3 postpartum (P = 0.002). Serum adiponectin concentrations at week 7 postpartum were lower in delayed C-LA (P = 0.01). Milk yield in cows with C-LA greater than 45 days increased more than cows with C-LA 45 days or less postpartum (P = 0.002). Insulin concentrations increased relatively in parallel from weeks 1 to 7 postpartum in cows either with C-LA greater than 45 or with C-LA 45 days or less. We showed for the first time the profile of serum adiponectin concentrations in a normal estrous cycle of dairy cows, and furthermore, it was found that high-producing dairy cows with higher postpartum serum adiponectin concentrations had NLA and earlier C-LA. Copyright © 2015 Elsevier Inc. All rights reserved.

Adiponectin improves insulin sensitivity via activation of autophagic flux.

PubMed

Ahlstrom, Penny; Rai, Esther; Chakma, Suharto; Cho, Hee Ho; Rengasamy, Palanivel; Sweeney, Gary

2017-11-01

Skeletal muscle insulin resistance is known to play an important role in the pathogenesis of diabetes, and one potential causative cellular mechanism is endoplasmic reticulum (ER) stress. Adiponectin mediates anti-diabetic effects via direct metabolic actions and by improving insulin sensitivity, and we recently demonstrated an important role in stimulation of autophagy by adiponectin. However, there is limited knowledge on crosstalk between autophagy and ER stress in skeletal muscle and in particular how they are regulated by adiponectin. Here, we utilized the model of high insulin/glucose (HIHG)-induced insulin resistance, determined by measuring Akt phosphorylation (T308 and S473) and glucose uptake in L6 skeletal muscle cells. HIHG reduced autophagic flux measured by LC3 and p62 Western blotting and tandem fluorescent RFP/GFP-LC3 immunofluorescence (IF). HIHG also induced ER stress assessed by thioflavin T/KDEL IF, pIRE1, pPERK, peIF2α and ATF6 Western blotting and induction of a GRP78-mCherry reporter. Induction of autophagy by adiponectin or rapamycin attenuated HIHG-induced ER stress and improved insulin sensitivity. The functional significance of enhanced autophagy was validated by demonstrating a lack of improved insulin sensitivity in response to adiponectin in autophagy-deficient cells generated by overexpression of dominant negative mutant of Atg5. In summary, adiponectin-induced autophagy in skeletal muscle cells alleviated HIHG-induced ER stress and insulin resistance. © 2017 Society for Endocrinology.

Lack of increase of serum adiponectin concentrations with a moderate weight loss during six months on a high-caloric diet in military service among a young male Finnish population.

PubMed

Mousavinasab, Firoozeh; Tähtinen, Tuula; Jokelainen, Jari; Koskela, Pentti; Vanhala, Mauno; Oikarinen, Jorma; Keinänen-Kiukaanniemi, Sirkka

2005-02-01

An increase of insulin resistance and a worsening of lipid profile during 6 mo of military service in young male Finnish population has previously been shown by us. The present study demonstrates unfavorable changes of serum adiponectin concentrations and their association with weight loss in these particular circumstances. Adiponectin in a range of 4.3-21.2 microg/mL was present in the serum samples and had a significant negative correlation with weight, body mass index, waist to hip ratio, and insulin. Fasting serum lipids and plasma insulin significantly increased and serum adiponectin levels significantly decreased during the military service. Even the subjects with a 5-10% decrease in body weight showed the same result. In cases with more than 10% weight reduction and a significant decrease of fasting insulin concentration, the total and low density lipoprotein cholesterol significantly increased and adiponectin concentration tended to decreased. Only in severely obese cases (BMI >/= 30 kg/m2) with more than 10% decrease in body mass index adiponectin levels tended to increase, although not statistically significantly. This study shows that serum adiponectin concentrations decreased during a 6 mo high-caloric diet in military service, and even a moderate weight reduction induced by high-energy expenditure in exercise during service did not increase its levels.

Recipient But Not Donor Adiponectin Polymorphisms Are Associated With Early Posttransplant Hepatic Steatosis in Patients Transplanted for Non-Nonalcoholic Fatty Liver Disease Indications.

PubMed

John, Binu V; Aiken, Taylor; Garber, Ari; Thomas, Dawn; Lopez, Rocio; Patil, Deepa; Konjeti, Venkata Rajesh; Fung, John J; McCollough, Arthur J; Askar, Medhat

2018-06-01

De novo steatosis after liver transplant is common and can occur in up to one-third of patients who are transplanted for liver disease other than for nonalcoholic fatty liver disease. Genetic factors may influence posttransplant steatosis; in a posttransplant setting, donor or recipient genetic factors could also play roles. Genetic polymorphisms in the adiponectin gene have been associated with metabolic syndrome in the pretransplant setting. We aimed to assess the association between donor and recipient adiponectin polymorphisms and early posttransplant hepatic steatosis identified on liver biopsies. Clinical data were collected for 302 liver transplant patients who underwent protocol biopsies for hepatitis C. Of these, 111 patients had available biopsies and donor/recipient DNA. Patients with grade 1 steatosis or greater (35% of patients) were compared with patients without posttransplant steatosis with respect to clinical features and donor/recipient adiponectin polymorphism genotypes. Patients who developed posttransplant steatosis and those without steatosis were similar with respect to individual components of metabolic syndrome. The adiponectin polymorphisms rs1501299 G/G and rs17300539 G/G genotypes in recipients were associated with early posttransplant graft steatosis. We found no associations between graft steatosis and donor adiponectin polymorphisms. Genetic polymorphisms in the adiponectin gene of recipients (but not donors) are associated with early de novo posttransplant hepatic steatosis, independent of components of metabolic syndrome.

Adiponectin isoform patterns in ethnic-specific ADIPOQ mutation carriers: The IRAS Family Study

PubMed Central

Tabb, Keri L.; Gao, Chuan; Hicks, Pamela J.; Hawkins, Gregory A.; Rotter, Jerome I.; da Chen, Yii-Der I; Guo, Xiuqing; Norris, Jill M.; Lorenzo, Carlos; Freedman, Barry I.; Bowden, Donald W.; Palmer, Nicholette D.

2017-01-01

Objective Adiponectin is found in human serum in three groups of multimers (high, medium, and low molecular weight). Previously, we reported two ethnic-specific variants in ADIPOQ, G45R (Hispanic Americans) and R55C (African Americans). Although carriers of both variants had mean adiponectin levels ≤20% of those of non-carriers, they were not clinically different from non-carriers. To compare carriers of both variants and non-carriers, relative quantification of adiponectin isoforms to total adiponectin was performed on serum samples. Methods The multimeric patterns of serum adiponectin in G45R carriers (n=23), R55C carriers (n=3), and Hispanic and African American non-carriers (n=84 and 44, respectively) from the IRAS Family Study were explored using native western blotting and densitometry. Results Serum samples from carriers showed an absence of the high molecular weight (HMW) isoform and a marked reduction in the medium molecular weight isoform but an approximate two-fold increase in the amount of the low molecular weight isoform (LMW). Thus, individuals making only LMW adiponectin are metabolically normal. Conclusions The results contrast with the proposed biological importance of the HMW multimer. This suggests that the LMW isoform may functionally compensate for some of the loss/reduction of the higher-order multimers in carriers of the G45R and R55C mutations. PMID:28643464

Regulation of intracellular trafficking and secretion of adiponectin by myosin II.

PubMed

Bedi, Deepa; Dennis, John C; Morrison, Edward E; Braden, Tim D; Judd, Robert L

2017-08-19

Adiponectin is a protein secreted by white adipocytes that plays an important role in insulin action, energy homeostasis and the development of atherosclerosis. The intracellular localization and trafficking of GLUT4 and leptin in adipocytes has been well studied, but little is known regarding the intracellular trafficking of adiponectin. Recent studies have demonstrated that constitutive adiponectin secretion is dependent on PIP2 levels and the integrity of cortical F-actin. Non-muscle myosin II is an actin-based motor that is associated with membrane vesicles and participates in vesicular trafficking in mammalian cells. Therefore, we investigated the role of myosin II in the trafficking and secretion of adiponectin in 3T3-L1 adipocytes. Confocal microscopy revealed that myosin IIA and IIB were dispersed throughout the cytoplasm of the adipocyte. Both myosin isoforms were localized in the Golgi/TGN region as evidenced by colocalization with the cis-Golgi marker, p115 and the trans-Golgi marker, γ-adaptin. Inhibition of myosin II activity by blebbistatin or actin depolymerization by latrunculin B dispersed myosin IIA and IIB towards the periphery while significantly inhibiting adiponectin secretion. Therefore, the constitutive trafficking and secretion of adiponectin in 3T3-L1 adipocytes occurs by an actin-dependent mechanism that involves the actin-based motors, myosin IIA and IIB. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of leptin and adiponectin on proliferation and protein metabolism of porcine myoblasts.

PubMed

Will, Katja; Kalbe, Claudia; Kuzinski, Judith; Lösel, Dorothea; Viergutz, Torsten; Palin, Marie-France; Rehfeldt, Charlotte

2012-08-01

The aim of this study was to show the abundance of leptin and adiponectin receptors (LEPR, ADIPOR1, ADIPOR2) and to determine the direct effects of leptin and adiponectin on the in vitro growth of porcine skeletal muscle cells. ADIPOR1 and ADIPOR2 were abundant at mRNA and protein level in proliferating and differentiating myoblast cultures derived from semimembranosus and semitendinosus muscles of newborn piglets, whereas LEPR expression was close to the detection limit. Adiponectin (10, 20, 40 μg/ml) attenuated the proliferation of porcine myoblasts, measured as [(3)H]-thymidine incorporation and real-time monitoring of the cells in response to 24- and 48-h exposure, in a dose-dependent manner. This effect resulted from suppressed basic fibroblast growth factor (bFGF)-mediated stimulation of DNA synthesis in serum-free medium (SFM) containing bFGF. No effects of leptin (5, 10, 20, 40, 80 ng/ml) on myoblast proliferation in SFM were detectable. Neither leptin nor adiponectin altered protein synthesis and degradation in differentiating porcine myoblasts cultured in SFM. The results on receptor abundance suggest that porcine skeletal muscle cells may be sensitive to adiponectin and leptin. However, except via inhibitory interaction of adiponectin with bFGF, these adipokines appear not to affect in vitro proliferation and protein metabolism of porcine muscle cells directly under serum-free culture conditions.

Dietary glycemic factors, insulin resistance, and adiponectin levels in acne vulgaris.

PubMed

Çerman, Aslı Aksu; Aktaş, Ezgi; Altunay, İlknur Kıvanç; Arıcı, Janset Erkul; Tulunay, Aysın; Ozturk, Feyza Yener

2016-07-01

There is increasing evidence to support the relationship between acne vulgaris and diet. The aim of this study was to investigate possible associations among dietary glycemic index, glycemic load, milk consumption, insulin resistance, and adiponectin levels in the pathogenesis of acne vulgaris. The dietary glycemic index, glycemic load, milk consumption, fasting glucose, insulin, insulin-like growth factor)-1, insulin-like growth factor binding protein-3, adiponectin, and homeostasis model assessment of insulin resistance values of 50 patients with acne vulgaris and 36 healthy control subjects were measured. Glycemic index and glycemic load levels were significantly higher (P = .022 and P = .001, respectively) and serum adiponectin levels were significantly lower (P = .015) in patients with acne than in the control subjects. There was an inverse correlation between serum adiponectin concentration and glycemic index (P = .049, r = -0.212). This study used a cross-sectional design and the study population was limited to young, nonobese adults. A high-glycemic-index/-load diet was positively associated with acne vulgaris. Adiponectin may be a pathogenetic cofactor contributing to the development of the disease. Further research on adiponectin levels in patients with acne in terms of development of insulin resistance might be important in this possible relationship. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Deep Resequencing Unveils Genetic Architecture of ADIPOQ and Identifies a Novel Low-Frequency Variant Strongly Associated With Adiponectin Variation

PubMed Central

Warren, Liling L.; Li, Li; Nelson, Matthew R.; Ehm, Margaret G.; Shen, Judong; Fraser, Dana J.; Aponte, Jennifer L.; Nangle, Keith L.; Slater, Andrew J.; Woollard, Peter M.; Hall, Matt D.; Topp, Simon D.; Yuan, Xin; Cardon, Lon R.; Chissoe, Stephanie L.; Mooser, Vincent; Morris, Andrew D.; Palmer, Colin N.A.; Perry, John R.; Frayling, Timothy M.; Whittaker, John C.; Waterworth, Dawn M.

2012-01-01

Increased adiponectin levels have been shown to be associated with a lower risk of type 2 diabetes. To understand the relations between genetic variation at the adiponectin-encoding gene, ADIPOQ, and adiponectin levels, and subsequently its role in disease, we conducted a deep resequencing experiment of ADIPOQ in 14,002 subjects, including 12,514 Europeans, 594 African Americans, and 567 Indian Asians. We identified 296 single nucleotide polymorphisms (SNPs), including 30 amino acid changes, and carried out association analyses in a subset of 3,665 subjects from two independent studies. We confirmed multiple genome-wide association study findings and identified a novel association between a low-frequency SNP (rs17366653) and adiponectin levels (P = 2.2E–17). We show that seven SNPs exert independent effects on adiponectin levels. Together, they explained 6% of adiponectin variation in our samples. We subsequently assessed association between these SNPs and type 2 diabetes in the Genetics of Diabetes Audit and Research in Tayside Scotland (GO-DARTS) study, comprised of 5,145 case and 6,374 control subjects. No evidence of association with type 2 diabetes was found, but we were also unable to exclude the possibility of substantial effects (e.g., odds ratio 95% CI for rs7366653 [0.91–1.58]). Further investigation by large-scale and well-powered Mendelian randomization studies is warranted. PMID:22403302

Adiponectin Suppresses UVB-Induced Premature Senescence and hBD2 Overexpression in Human Keratinocytes

PubMed Central

Kim, MinJeong; Park, Kui Young; Lee, Mi-Kyung; Jin, Taewon; Seo, Seong Jun

2016-01-01

Recent studies have revealed that adiponectin can suppress cellular inflammatory signaling pathways. This study aimed to elucidate the effect of adiponectin on the unregulated production of hBD2 in UVB-induced premature senescent keratinocytes. We constructed an in vitro model of premature senescent keratinocytes through repeated exposure to low energy UVB. After repeated low energy UVB exposure, there was significant generation of reactive oxygen species (ROS) and induction of senescence-associated markers, including senescence associated beta-galactosidase activity and expression of p16INK4a and histone H2AX. In addition, the present clinical study showed higher expression of hBD2 in sun-exposed skin of elderly group, and the overexpression of hBD2 was observed by c-Fos activation in vitro. Adiponectin has the ability to scavenge ROS and consequently inhibit MAPKs and SA-markers in UVB-exposed keratinocytes. An inhibitor study demonstrated that adiponectin downregulated hBD2 mRNA expression through suppression of the AP-1 transcription factor components c-Fos via inactivation of p38 MAPK. Collectively, the dysregulated production of hBD2 by the induction of oxidative stress was attenuated by adiponectin through the suppression of p38 and JNK/SAPK MAPK signaling in UVB-mediated premature senescent inducible conditions. These results suggest the feasibility of adiponectin as an anti-photoaging and anti-inflammatory agent in the skin. PMID:27526049

Effects of pasteurization on adiponectin and insulin concentrations in donor human milk.

PubMed

Ley, Sylvia H; Hanley, Anthony J; Stone, Debbie; O'Connor, Deborah L

2011-09-01

Although pasteurization is recommended before distributing donor human milk in North America, limited data are available on its impact on metabolic hormones in milk. We aimed to investigate the effects of pasteurization on adiponectin and insulin concentrations in donor human milk. The study investigates concentrations of components in donor human milk before and after Holder pasteurization. After the guidelines of the Human Milk Bank Association of North America, human milk samples were pooled to produce 17 distinct batches (4 individuals per batch) and pasteurized at 62.5°C for 30 min. Adiponectin, insulin, energy, fat, total protein, and glucose concentrations were measured pre- and postpasteurization. Pasteurization reduced milk adiponectin and insulin by 32.8 and 46.1%, respectively (both p < 0.0001). Adiponectin and insulin were significantly correlated with energy and fat milk composition (r = 0.36-0.47; all p < 0.05). Pasteurization effects on milk hormone concentrations remained significant after adjusting for fat and energy (beta ± SEE: -4.11 ± 1.27, p = 0.003 for adiponectin; -70.0 ± 15.0, p < 0.0001 for insulin). Holder pasteurization reduced adiponectin and insulin concentrations in donor human milk. In view of emerging knowledge on the importance of milk components, continued work to find the optimal pasteurization process that mitigates risks but promotes retention of bioactive components is needed.

Adiponectin: an independent risk factor for coronary heart disease in men in the Framingham Offspring Study

USDA-ARS?s Scientific Manuscript database

Our aim was to determine whether plasma adiponectin levels were an independent predictor of coronary heart disease (CHD) risk. Plasma adiponectin levels were measured in 3,188 male and female participants from cycle 6 of the Framingham Offspring Study (mean age: 57 years in both men and women; BMI:...

Effect of hormonal and energy-related factors on plasma adiponectin in transition dairy cows.

PubMed

Krumm, C S; Giesy, S L; Caixeta, L S; Butler, W R; Sauerwein, H; Kim, J W; Boisclair, Y R

2017-11-01

In transition dairy cows, plasma levels of the insulin-sensitizing hormone adiponectin fall to a nadir at parturition and recover in early lactation. The transition period is also characterized by rapid changes in metabolic and hormonal factors implicated in other species as positive regulators of adiponectin production (i.e., negative energy balance, lipid mobilization) and others as negative regulators (i.e., reduced leptin and insulin and increased growth hormone and plasma fatty acids). To assess the role of onset of negative energy balance and lipid mobilization after parturition, dairy cows were either milked thrice daily (lactating) or never milked (nonlactating) for up to 4 wk after parturition. Plasma adiponectin was 21% higher across time in nonlactating than lactating cows. Moreover, nonlactating cows recovered plasma adiponectin at similar rates as lactating cows even though they failed to lose body condition. Next, we assessed the ability of individual hormones to alter plasma adiponectin in transition dairy cows. In the first experiment, dairy cows received a constant 96-h intravenous infusion of either saline or recombinant human leptin starting on d 8 of lactation. In the second experiment, dairy cows were studied in late pregnancy (LP, starting on prepartum d -31) and again in early lactation (EL, starting on d 7 postpartum) during a 66-h period of basal sampling followed by 48 h of hyperinsulinemic-euglycemia. In the third experiment, cows were studied either in LP (starting on d -40 prepartum) or EL (starting on d 7 postpartum) during a 3-h period of basal sampling followed by 5 d of bovine somatotropin treatment. Plasma adiponectin was reduced by an average of 21% in EL relative to LP in these experiments, but neither leptin, insulin, or growth hormone treatment affected adiponectin in LP or EL. Finally, the possibility that plasma fatty acids repress plasma adiponectin was evaluated by intravenous infusion of a lipid emulsion in nonpregnant, nonlactating cows in the absence or presence of glucagon for 16 consecutive hours. The intralipid infusion increased plasma fatty acid concentration from 102 to over 570 µM within 3 h but had no effect on plasma adiponectin irrespective of presence or absence of glucagon. Overall, these data suggest that energy balance around parturition may regulate plasma adiponectin but do not support roles for lipid mobilization or sustained changes in the plasma concentration of leptin, insulin, growth hormone, or fatty acids. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Expression of adiponectin and its receptors in the porcine hypothalamus during the oestrous cycle.

PubMed

Kaminski, T; Smolinska, N; Maleszka, A; Kiezun, M; Dobrzyn, K; Czerwinska, J; Szeszko, K; Nitkiewicz, A

2014-06-01

Adiponectin is a hormonal link between obesity and reproduction, and its actions are mediated by two types of receptors: adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). This study compares the expression levels of adiponectin and adiponectin receptor mRNAs and proteins in selected areas of the porcine hypothalamus responsible for GnRH production and secretion: the mediobasal hypothalamus (MBH), pre-optic area (POA) and stalk median eminence (SME). The tissue samples were harvested on days 2-3, 10-12, 14-16 and 17-19 of the oestrous cycle. Adiponectin mRNA expression in MBH was significantly lower on days 14-16, whereas in SME, the most pronounced gene expression was found on days 2-3 of the cycle (p < 0.05). Adiponectin protein in MBH was most abundant on days 17-19 and in POA on days 2-3 (p < 0.05). Adiponectin protein expression in SME was at similar level throughout the most of the cycle with a statistically significant drop (p < 0.05) on days 14-16. AdipoR1 gene expression in POA was potentiated on days 2-3 and 10-12 of the oestrous cycle (p < 0.05). In SME, the highest AdipoR1 mRNA expression was noted on days 2-3 (p < 0.05). The concentrations of the AdipoR1 protein in POA were similar throughout the luteal phase (days 2-14 of the cycle), and they decreased on days 17-19 (p < 0.05). In SME, AdipoR1 protein expression peak occurred on days 2-3 (p < 0.05). The expression patterns of the AdipoR2 gene in MBH, POA and SME revealed the highest mRNA levels on days 2-3 of the cycle (p < 0.05). The highest content of AdipoR2 protein in MBH was reported on days 2-3 (p < 0.05), while in POA on days 17-19 and in SME on days 10-12 and 14-16 (p < 0.05). This study demonstrated that adiponectin and adiponectin receptor mRNAs and proteins are present in the porcine hypothalamus and that their expression levels are determined by the pig's endocrine status related to the oestrous cycle. © 2014 Blackwell Verlag GmbH.

Functional Characterization of Promoter Variants of the Adiponectin Gene Complemented by Epidemiological Data

PubMed Central

Laumen, Helmut; Saningong, Akuma D.; Heid, Iris M.; Hess, Jochen; Herder, Christian; Claussnitzer, Melina; Baumert, Jens; Lamina, Claudia; Rathmann, Wolfgang; Sedlmeier, Eva-Maria; Klopp, Norman; Thorand, Barbara; Wichmann, H.-Erich; Illig, Thomas; Hauner, Hans

2009-01-01

OBJECTIVE Adiponectin (APM1, ACDC) is an adipocyte-derived protein with downregulated expression in obesity and insulin-resistant states. Several potentially regulatory single nucleotide polymorphisms (SNPs) within the APM1 gene promoter region have been associated with circulating adiponectin levels. None of them have been functionally characterized in adiponectin-expressing cells. Hence, we investigated three SNPs (rs16861194, rs17300539, and rs266729) for their influence on adiponectin promoter activity and their association with circulating adiponectin levels. RESEARCH DESIGN AND METHODS Basal and rosiglitazone-induced promoter activity of different SNP combinations (haplotypes) was analyzed in 3T3-L1 adipocytes using luciferase reporter gene assays and DNA binding studies comparing all possible APM1 haplotypes. This functional approach was complemented with analysis of epidemiological population-based data of 1,692 participants of the MONICA/KORA S123 cohort and 696 participants from the KORA S4 cohort for SNP and haplotype association with circulating adiponectin levels. RESULTS Major to minor allele replacements of the three SNPs revealed significant effects on promoter activity in luciferase assays. Particularly, a minor variant in rs16861194 resulted in reduced basal and rosiglitazone-induced promoter activity and hypoadiponectinemia in the epidemiological datasets. The haplotype with the minor allele in all three SNPs showed a complete loss of promoter activity, and no subject carried this haplotype in either of the epidemiological samples (combined P value for statistically significant difference from a random sample was 0.006). CONCLUSIONS Our results clearly demonstrate that promoter variants associated with hypoadiponectinemia in humans substantially affect adiponectin promoter activity in adipocytes. Our combination of functional experiments with epidemiological data overcomes the drawback of each approach alone. PMID:19074982

Relation of adiponectin and high-sensitivity C-reactive protein to pulse-wave velocity and N-terminal pro-B-type natriuretic peptide in the general population.

PubMed

Sung, Shih-Hsien; Chuang, Shao-Yuan; Sheu, Wayne Huey-Herng; Lee, Wen-Jane; Chou, Pesus; Chen, Chen-Huan

2009-05-15

The roles of metabolic syndrome and chronic subclinical inflammation in arterial stiffening and the development of heart failure remain to be elucidated. Whether adiponectin and high-sensitivity C-reactive protein (hs-CRP) were independently related to brachial-ankle pulse-wave velocity (ba-PWV) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in the general population were investigated. Eligible study subjects were 445 Chinese residents aged > or =40 years who participated in a community-based survey, underwent examination of ba-PWV, and had complete data of serum adiponectin, hs-CRP (<10 mg/L), and NT-pro-BNP. Adiponectin, but not hs-CRP, was independently related to ba-PWV (standardized regression parameter -0.107, p <0.05) when age, gender, body mass index, and number of metabolic syndrome components were accounted for. On the other hand, ba-PWV, adiponectin, and hs-CRP were independently related to NT-pro-BNP (standardized regression parameters 0.116, 0.188, and 0.094, respectively; all p <0.05) when age, gender, body mass index, number of metabolic syndrome components, and renal function were accounted for. In conclusion, adiponectin, but not hs-CRP, is independently associated with both ba-PWV and NT-pro-BNP in the general population. Because adiponectin, hs-CRP, ba-PWV, and NT-pro-BNP may represent markers for metabolic syndrome, chronic subclinical inflammation, arterial stiffness, and ventricular dysfunction, respectively, our results suggest that adiponectin may directly modulate both arterial stiffening and ventricular dysfunction. In contrast, hs-CRP may independently contribute to ventricular dysfunction, but not arterial stiffening.

Associations of Insulin Resistance and Adiponectin With Mortality in Women With Breast Cancer

PubMed Central

Duggan, Catherine; Irwin, Melinda L.; Xiao, Liren; Henderson, Katherine D.; Smith, Ashley Wilder; Baumgartner, Richard N.; Baumgartner, Kathy B.; Bernstein, Leslie; Ballard-Barbash, Rachel; McTiernan, Anne

2011-01-01

Purpose Overweight or obese breast cancer patients have a worse prognosis compared with normal-weight patients. This may be attributed to hyperinsulinemia and dysregulation of adipokine levels associated with overweight and obesity. Here, we evaluate whether low levels of adiponectin and a greater level of insulin resistance are associated with breast cancer mortality and all-cause mortality. Patients and Methods We measured glucose, insulin, and adiponectin levels in fasting serum samples from 527 women enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer. We evaluated the association between adiponectin and insulin and glucose levels (expressed as the Homeostatic Model Assessment [HOMA] score) represented as continuous measures and median split categories, along with breast cancer mortality and all-cause mortality, using Cox proportional hazards models. Results Increasing HOMA scores were associated with reduced breast cancer survival (hazard ratio [HR], 1.12; 95% CI, 1.05 to 1.20) and reduced all-cause survival (HR, 1.09; 95% CI, 1.02 to 1.15) after adjustment for possible confounders. Higher levels of adiponectin (above the median: 15.5 μg/mL) were associated with longer breast cancer survival (HR, 0.39; 95% CI, 0.15 to 0.95) after adjustment for covariates. A continuous measure of adiponectin was not associated with either breast cancer–specific or all-cause mortality. Conclusion Elevated HOMA scores and low levels of adiponectin, both associated with obesity, were associated with increased breast cancer mortality. To the best of our knowledge, this is the first demonstration of the association between low levels of adiponectin and increased breast cancer mortality in breast cancer survivors. PMID:21115858

ASSOCIATIONS OF ADIPONECTIN, LEPTIN LEVELS, AND THE CHANGE OF BODY COMPOSITION IN PATIENTS ON PERITONEAL DIALYSIS: A PROSPECTIVE COHORT STUDY.

PubMed

Xu, Xiao; Tian, Xue; Chen, Yuan; Yang, Zhi-Kai; Qu, Zhen; Dong, Jie

2018-04-19

Although the association between adipokines such as adiponectin, leptin, and body composition has been noted, whether they could predict the change of fat mass and lean body mass is unknown. We aimed to examine these associations in patients on peritoneal dialysis (PD) through a prospective cohort study. Body composition (by dual-energy x-ray absorptiometry) including fat mass and lean body mass were examined at baseline and then at year 3. Serum leptin and adiponectin levels were measured. Demographic data, comorbidity, biochemical data, inflammation (high-sensitive C-reactive protein [hs-CRP]) and insulin resistance (homeostatic model assessment [HOMA-IR]) were also examined. At baseline, serum adiponectin levels were significantly inversely correlated with weight, lean body mass index (LBMI), fat mass index (FMI), lean body mass (LBM), and fat mass (FM) in 213 prevalent patients. At year 3, FMI, LBMI, FM, and the percentage of FM (FM%) increased while the percentage of LBM (LBM%) significantly decreased despite unchanged weight and LBM among the remaining 112 patients. After adjustment for demographic data, comorbidities, hs-CRP, HOMA-IR, and daily energy intake (DEI), serum adiponectin at baseline was not associated with increases in LBMI, FMI, and FM, but independently associated with an increase in FM% and a decrease in LBM%. The predictive effect of high-serum adiponectin level on mortality disappeared after adjusting for diabetes and cardiovascular disease. Serum leptin was not associated with any changes in body composition during the follow-up, nor with the mortality in this cohort. A high adiponectin level could predict an increase in FM% and a decrease in LBM% during a 3-year follow-up in PD patients. Serum adiponectin could not independently predict mortality in PD patients.

Possible implications of leptin, adiponectin and ghrelin in the regulation of energy homeostasis by thyroid hormone.

PubMed

Kokkinos, Alexander; Mourouzis, Iordanis; Kyriaki, Despoina; Pantos, Constantinos; Katsilambros, Nicholas; Cokkinos, Dennis V

2007-08-01

Thyroid hormone plays a critical role in energy homeostasis through mechanisms, which are not fully understood. In the present study, we investigated possible alterations of important energy regulators such as leptin, adiponectin, and ghrelin in relation to changes in thyroid hormones. Thyroid hormone (250 microg/kg) was administered in male Wistar rats for 2 weeks (THYR), while hypothyroidism (HYPO) was induced by propylthiouracil administration (0.05% in drinking water) for 3 weeks. Untreated animals served as controls (NORM). Leptin and adiponectin were measured in plasma by ELISA, while total ghrelin was measured with RIA. Body weight was significantly reduced both in THYR and HYPO rats, while food intake was significantly increased in THYR and decreased in HYPO. This response was associated with various changes in leptin, adiponectin, and ghrelin in plasma. In fact, in THYR rats, leptin levels (mean +/- SEM) were 240 +/- 55 pg/ml as compared to 819 +/- 70 pg/ml in untreated rats (P < 0.05), while no changes were observed in ghrelin and adiponectin. In HYPO rats, leptin levels were 1400 +/- 200 pg/ml vs. 819 +/- 70 pg/ml in untreated rats (P < 0.05), while ghrelin and adiponectin were significantly increased in HYPO rats as compared to untreated rats (P < 0.05). Furthermore, T(3) and T(4) levels were inversely correlated to leptin (P = 0.014), while ghrelin and adiponectin were inversely correlated to weight changes (P = 0.05 and P = 0.03, respectively). In conclusion, leptin seems mainly to be involved in the thyroid hormone effects on energy homeostasis. Ghrelin and adiponectin may serve a compensatory physiological role in hypothyroidism.

Effects of a combination of rhGH and metformin on adiponectin levels in patients with metabolic syndrome.

PubMed

Herrmann, B L; Saller, B; Stratmann, M; Berg, C; Mann, K; Janssen, O E

2005-01-01

Adiponectin is a recently discovered adipocytokine that correlates negatively with body mass index and body fat. In patients with GH deficiency, treatment with recombinant human growth hormone (rhGH) reduces body fat mass and thus may also have a favorable effect in patients with metabolic syndrome, and would also be expected to increase adiponectin levels. However, due to its diabetogenic effect, rhGH treatment also bears an increased risk for the development of type 2 diabetes mellitus. We conducted a 18-month randomized, double-blind, placebo-controlled study to assess the effect of rhGH in combination with metformin (MGH) in 14 obese men (7 MGH; 7 Metformin+Placebo, 54 +/- 2 years, BMI 33.0 +/- 1.2 kg/m(2)) with mildly elevated fasting plasma glucose (FPG) at screening (6.1-8.0 mmol/l). All patients received metformin (850 mg twice daily) for treatment of type 2 diabetes mellitus/impaired glucose tolerance, either alone or in combination with rhGH (daily dose 9.5 mug/kg body weight). Glucose disposal rate (GDR) was measured using the euglycemic hyperinsulinemic clamp technique, and body composition was measured by DEXA at 0 and 18 months. After 18 months, the mean adiponectin concentration increased by 32 +/- 11 % (p = 0.018) in the MGH group and did not change in the MP group (- 10 +/- 13 %; p = n. s.). The difference in relative changes in adiponectin levels between the two groups after 18 months was statistically significant (p = 0.026). Improvement in insulin sensitivity (GDR) correlated positively with adiponectin levels (r = 0.73; p = 0.004). In conclusion, the additional administration of rhGH increased adiponectin levels in patients with metabolic syndrome, indicating its potential role in adiponectin-associated insulin sensitivity alterations.

Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet.

PubMed

Flachs, P; Mohamed-Ali, V; Horakova, O; Rossmeisl, M; Hosseinzadeh-Attar, M J; Hensler, M; Ruzickova, J; Kopecky, J

2006-02-01

Diets rich in n-3 polyunsaturated fatty acids, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against insulin resistance and obesity in rodents and increase insulin sensitivity in healthy humans. We tested whether the anti-diabetic effects of EPA and DHA involve enhanced production of the endogenous insulin sensitiser, adiponectin. We studied the effects, in an obesity-promoting high-fat diet, of partial replacement of vegetable oils by EPA/DHA concentrate (6% EPA, 51% DHA) over a 5-week period in adult male C57BL/6J mice that either had free access to food or had their food intake restricted by 30%. At the end of the treatment, systemic markers of lipid and glucose metabolism and full-length adiponectin and leptin were measured. Adiponectin (Adipoq) and leptin (Lep) gene expression in dorsolumbar and epididymal white adipose tissue (WAT) and isolated adipocytes was quantified and adipokine production from WAT explants evaluated. In mice with free access to food, plasma triacylglycerols, NEFA, and insulin levels were lower in the presence of EPA/DHA, while glucose and leptin levels were not significantly altered. Food restriction decreased plasma triacylglycerols, glucose, insulin and leptin, but not adiponectin. EPA/DHA increased plasma adiponectin levels, independent of food intake, reflecting the stimulation of Adipoq expression in adipocytes and the release of adiponectin from WAT, particularly from epididymal fat. Expression of Lep and the release of leptin from WAT, while being extremely sensitive to caloric restriction, was unaltered by EPA/DHA. Intake of diets rich in EPA and DHA leads to elevated systemic concentrations of adiponectin, largely independent of food intake or adiposity and explain, to some extent, their anti-diabetic effects.

Gene expression of leptin, resistin, and adiponectin in the white adipose tissue of obese patients with non-alcoholic fatty liver disease and insulin resistance.

PubMed

Baranova, Ancha; Gowder, Shobha J; Schlauch, Karen; Elariny, Hazem; Collantes, Rochelle; Afendy, Arian; Ong, Janus P; Goodman, Zachary; Chandhoke, Vikas; Younossi, Zobair M

2006-09-01

Adipose tissue is an active endocrine organ that secretes a variety of metabolically important substances including adipokines. These factors affect insulin sensitivity and may represent a link between obesity, insulin resistance, type 2 diabetes (DM), and nonalcoholic fatty liver disease (NAFLD). This study uses real-time polymerase chain reaction (PCR) quantification of mRNAs encoding adiponectin, leptin, and resistin on snap-frozen samples of intra-abdominal adipose tissue of morbidly obese patients undergoing bariatric surgery. Morbidly obese patients undergoing bariatric surgery were studied. Patients were classified into two groups: Group A (with insulin resistance) (N=11; glucose 149.84 +/- 40.56 mg/dL; serum insulin 8.28 +/- 3.52 microU/mL), and Group B (without insulin resistance) (N=10; glucose 102.2 +/- 8.43 mg/dL; serum insulin 3.431 +/- 1.162 microU/mL). Adiponectin mRNA in intra-abdominal adipose tissue and serum adiponectin levels were significantly lower in Group A compared to Group B patients (P<0.016 and P<0.03, respectively). Although serum resistin was higher in Group A than in Group B patients (P<0.005), resistin gene expression was not different between the two groups. Finally, for leptin, neither serum level nor gene expression was different between the two groups. Serum adiponectin level was the only predictor of nonalcoholic steatohepatitis (NASH) in this study (P=0.024). Obese patients with insulin resistance have decreased serum adiponectin and increased serum resistin. Additionally, adiponectin gene expression is also decreased in the adipose tissue of these patients. This low level of adiponectin expression may predispose patients to the progressive form of NAFLD or NASH.

Adiponectin limits monocytic microparticle-induced endothelial activation by modulation of the AMPK, Akt and NFκB signaling pathways.

PubMed

Ehsan, Mehroz; Singh, Krishna K; Lovren, Fina; Pan, Yi; Quan, Adrian; Mantella, Laura-Eve; Sandhu, Paul; Teoh, Hwee; Al-Omran, Mohammed; Verma, Subodh

2016-02-01

Monocyte-derived microparticles (mono-MPs) are emerging as critical transducers of inflammatory signals, and have been suggested to link cardiovascular risk factors to vascular injury. Since adiponectin has been proposed to exert multiple anti-inflammatory and vasculoprotective effects, we hypothesized that it might serve to limit the production and/or action of mono-MPs. Flow cytometry and western blot studies were conducted on THP-1 cells, THP-1-derived MPs, human umbilical vein endothelial cells (HUVECs), peripheral blood CD14+ monocytes and mice to evaluate the effects of adiponectin on mono-MPs. Adiponectin attenuated lipopolysaccharide (LPS)-evoked MP release from THP-1 monocytes (30% difference) and peripheral blood monocytes (both P < 0.05) as well as dampened LPS-induced mono-MP generation in vivo. Furthermore, peritoneal monocytes from Adipoq(-/-) mice generated significantly greater MPs than those from Adipoq(+/+) littermates in the absence (2.3 fold difference, P < 0.05) and presence (1.6 fold difference, P < 0.05) of LPS. LPS-induced MP expression of NLRP3 inflammasome and its key components, namely cleaved ASC, caspase-1 and IL-1β (pro- and cleaved), were markedly attenuated by adiponectin. HUVECs incubated with MPs from LPS-treated THP-1 cells exhibited increased VCAM-1 levels and adhesion to THP-1 cells. Adiponectin abrogated these effects. From a mechanistic standpoint, the effects of adiponectin on MP release and molecular signaling occurred at least in part through the AMPK, Akt and NFκB pathways. Adiponectin exerts novel effects to limit the production and action of mono-MPs, underscoring yet another pleiotropic effect of this adipokine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of Body Fat on the Associations of High-Molecular-Weight Adiponectin, Leptin and Soluble Leptin Receptor with Metabolic Syndrome in Chinese

PubMed Central

Yu, Danxia; Yu, Zhijie; Sun, Qi; Sun, Liang; Li, Huaixing; Song, Jun; Mi, Ming; Wu, Hongyu; Lu, Ling; Liu, Chen; Zhang, Geng; Hu, Frank B.; Lin, Xu

2011-01-01

Background Little is known regarding the associations between high-molecular-weight (HMW-) adiponectin, leptin and soluble leptin receptor (sOB-R) and metabolic syndrome (MetS) in Chinese. Also few studies elucidate the effects of inflammation and body fat mass on the relations. Methods Plasma HMW-adiponectin, leptin and sOB-R were measured among 1055 Chinese men and women (35∼54 yrs). Whole body and trunk fat mass were determined by Dual-energy X-ray absorptiometry. MetS was defined by the updated NCEP/ATPIII criterion for Asian-Americans. Results HMW-adiponectin was inversely associated with MetS in multivariate model including fat mass index (FMI), inflammatory markers, leptin and sOB-R (OR in the highest quartile  = 0.30, 95%CI 0.18∼0.50, P<.0001). Plasma sOB-R was also inversely associated with MetS independent of body fatness and inflammatory markers, whereas the association was somewhat attenuated after adjusting HMW-adiponectin (OR for the highest quartile  = 0.78, 95%CI 0.47∼1.32, P = 0.15). In contrast, leptin was associated with increased odds of MetS independent of inflammatory markers, HMW-adiponectin, and sOB-R (OR for the highest quartile  = 2.64, 95%CI 1.35∼5.18, P = 0.006), although further adjustment for FMI abolished this association. Conclusions HMW-adiponectin exhibited strong inverse associations with MetS independent of body composition, inflammation, leptin and sOB-R; while the associations of leptin and sOB-R were largely explained by fat mass or HMW-adiponectin, respectively. PMID:21347230

Adiponectin, Leptin and Objectively Measured Physical Activity in Adults: A Narrative Review

PubMed Central

Nurnazahiah, Ali; Lua, Pei Lin; Shahril, Mohd Razif

2016-01-01

The objective of this study was to compile and analyse existing scientific evidences reporting the effects of objectively measured physical activity on the levels of adiponectin and leptin. Articles related to the effects of objectively measured physical activity on the levels of adiponectin and leptin were searched from the Medline and PubMed databases. The search was limited to ‘objectively measured’ physical activity, and studies that did not objectively measure the physical activity were excluded. Only English articles were included in the search and review. A total of 18 articles encompassing 2,026 respondents met the inclusion criteria. The eligible articles included all forms of evidence (e.g., cross-sectional and intervention). Seventeen and 11 studies showed the effects of objectively measured physical activity on adiponectin and leptin, respectively. Five and four cross-sectional studies showed the effects of objectively measured physical activity on adiponectin and leptin, respectively. Two out of five studies showed a weak to moderate positive association between adiponectin and objectively measured physical activity, while three out of four studies showed a weak to moderate inverse association between leptin and objectively measured physical activity. For intervention studies, six out of 12 studies involving adiponectin and five out of seven studies involving leptin showed a significant effect between the proteins and objectively measured physical activity. However, a definitive conclusion could not be drawn due to several methodological flaws in the existing articles and the acute lack of additional research in this area. In conclusion, the existing evidences are encouraging but yet not compelling. Hence, further well-designed large trials are needed before the effectiveness of objectively measured physical activity in elevating adiponectin levels and in decreasing leptin levels could be strongly confirmed. PMID:28090175

Triiodothyronine modulates the expression of leptin and adiponectin in 3T3-L1 adipocytes

PubMed Central

de Oliveira, Miriane; Síbio, Maria Teresa De; Olimpio, Regiane Marques Castro; Moretto, Fernanda Cristina Fontes; Luvizotto, Renata de Azevedo Melo; Nogueira, Celia Regina

2015-01-01

Objective To study the effect of different doses of triiodothyronine on gene expression of the adipokines leptin and adiponectin, at different times, and to evaluate the difference in expression between the two adipokines in each group. Methods 3T3-L1 adipocytes were incubated with triiodothyronine at physiological dose (10nM) and supraphysiological doses (100nM or 1,000nM), or without triiodothyronine (control, C) for 0.5, 6, or 24 hours. Leptin and adiponectin mRNA was detected using real-time polymerase chain reaction (RT-PCR). One-way analyses of variance, Tukey’s test or Student’s t test, were used to analyze data, and significance level was set at 5%. Results Leptin levels decreased in the 1,000nM-dose group after 0.5 hour. Adiponectin levels dropped in the 10nM-dose group, but increased at the 100nM dose. After 6 hours, both genes were suppressed in all hormone concentrations. After 24 hours, leptin levels increased at 10, 100 and 1,000nM groups as compared to the control group; and adiponectin levels increased only in the 100nM group as compared to the control group. Conclusion These results demonstrated fast actions of triiodothyronine on the leptin and adiponectin expression, starting at 0.5 hour, at a dose of 1,000nM for leptin and 100nM for adiponectin. Triiodothyronine stimulated or inhibited the expression of adipokines in adipocytes at different times and doses which may be useful to assist in the treatment of obesity, assuming that leptin is increased and adiponectin is decreased, in obesity cases. PMID:25993072

Triiodothyronine modulates the expression of leptin and adiponectin in 3T3-L1 adipocytes.

PubMed

Oliveira, Miriane de; de Síbio, Maria Teresa; Olimpio, Regiane Marques Castro; Moretto, Fernanda Cristina Fontes; Luvizotto, Renata de Azevedo Melo; Nogueira, Celia Regina

2015-01-01

To study the effect of different doses of triiodothyronine on gene expression of the adipokines leptin and adiponectin, at different times, and to evaluate the difference in expression between the two adipokines in each group. 3T3-L1 adipocytes were incubated with triiodothyronine at physiological dose (10nM) and supraphysiological doses (100nM or 1,000nM), or without triiodothyronine (control, C) for 0.5, 6, or 24 hours. Leptin and adiponectin mRNA was detected using real-time polymerase chain reaction (RT-PCR). One-way analyses of variance, Tukey's test or Student's t test, were used to analyze data, and significance level was set at 5%. Leptin levels decreased in the 1,000nM-dose group after 0.5 hour. Adiponectin levels dropped in the 10nM-dose group, but increased at the 100nM dose. After 6 hours, both genes were suppressed in all hormone concentrations. After 24 hours, leptin levels increased at 10, 100 and 1,000nM groups as compared to the control group; and adiponectin levels increased only in the 100nM group as compared to the control group. These results demonstrated fast actions of triiodothyronine on the leptin and adiponectin expression, starting at 0.5 hour, at a dose of 1,000nM for leptin and 100nM for adiponectin. Triiodothyronine stimulated or inhibited the expression of adipokines in adipocytes at different times and doses which may be useful to assist in the treatment of obesity, assuming that leptin is increased and adiponectin is decreased, in obesity cases.

Serum adiponectin concentration in relation to macronutrient and food intake in young Japanese women.

PubMed

Murakami, Kentaro; Sasaki, Satoshi; Uenishi, Kazuhiro

2013-01-01

Little is known about the relation of modifiable dietary factors to circulating adiponectin concentrations, particularly in young adults and non-Western populations. The aim of this study was to determine the association between macronutrient and food intake and serum adiponectin concentration in a group of young Japanese women. This cross-sectional study included 1047 female Japanese dietetic students aged 18 to 22 y. Using a validated, self-administered, comprehensive diet history questionnaire, we assessed intake of nutrients (protein, total fat, saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids, carbohydrates, and dietary fiber) and foods (rice, bread, noodles, potatoes, confectioneries, fats and oils, pulses, fish and shellfish, meats, eggs, dairy products, vegetables, fruits, coffee, green and oolong tea, black tea, and soft drinks) and glycemic index and load. Fasting blood samples were collected and serum adiponectin concentrations were measured. Adjustment was made for survey year, region, municipality level, current smoking, current alcohol drinking, physical activity, body mass index, energy intake, and intakes of other nutrients or foods. After adjustment for potential confounding factors, none of the nutrients examined was a significant determinant of serum adiponectin concentration. There was no association for glycemic index or load. Coffee was the only food significantly and independently associated with serum adiponectin concentration. Mean (SE) values of serum adiponectin concentration for each quartile of coffee intake were 12.4 (0.2), 12.4 (0.5), 12.5 (0.3), and 13.2 (0.3) μg/mL, respectively (P for trend = 0.04). In a group of young Japanese women, higher coffee intake was independently associated with higher serum adiponectin concentration. Copyright © 2013 Elsevier Inc. All rights reserved.

Lower total and percent of high-molecular-weight adiponectin concentration in South Asian kidney transplant recipients

PubMed Central

Vorobeichik, Leon; Nash, Michelle M.; Huang, Michael; Rapi, Lindita; Maguire, Graham; Mamdani, Muhammad; Yan, Andrew T.; Connelly, Philip W.

2012-01-01

Background. Ethnicity is an important determinant of post-renal transplant outcomes. Limited data are available on cardiovascular risk differences in kidney transplant recipients (KTR) based on ethnicity. Methods. A group of 129 clinically stable age-matched KTR [43 South Asian (SA), 86 Caucasian]) were assessed for plasma total and high-molecular-weight (HMW) adiponectin, cystatin C, apolipoproteins A1 and B, C-reactive protein, uric acid, urine albumin-to-creatinine ratio, estimated glomerular filtration rate (eGFR) and transplant-specific plus traditional Framingham risk factors. SA and Caucasians were compared by t-tests, Wilcoxon rank-sum or chi-square testing. Accounting for the matched design, multivariable linear regression was performed to determine predictors of adiponectin concentrations. Results. SA did not differ from Caucasians in background cardiac disease or cardioprotective medication use or risk factors other than smoking (26 versus 56%, P = 0.001). Total adiponectin (9.5 ± 3.5 versus 12.9 ± 6.7 μmg/mL, P < 0.001) and HMW adiponectin (22 ± 9 versus 29 ± 11%, P < 0.001) were significantly lower in SA. Determinants of total adiponectin included SA ethnicity (P = 0.02), cystatin C-eGFR (P < 0.001), high-density lipoprotein (HDL) cholesterol (P < 0.0001) and waist-to-hip ratio (P < 0.001), while those of HMW adiponectin included SA ethnicity (P < 0.001), cystatin C-eGFR (P = 0.03) and HDL cholesterol (P = 0.001). There were no important differences in the other measured biomarkers. Conclusion. Total and HMW adiponectin concentrations are lower in SA KTR and may be promising exploratory biomarkers of post-transplant cardiovascular risk. PMID:24744849

Oxidative stress and inflammatory markers in relation to circulating levels of adiponectin.

PubMed

Gustafsson, Stefan; Lind, Lars; Söderberg, Stefan; Zilmer, Mihkel; Hulthe, Johannes; Ingelsson, Erik

2013-07-01

Previous epidemiological studies together with animal studies have suggested an association between adiponectin and oxidative stress and inflammation, but community-based studies are lacking. Our objective was to investigate the relative importance of oxidative stress and inflammatory markers, representing different pathways in relation to adiponectin. In a cross-sectional sample of 929 70-year-old individuals (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors study, relations between serum adiponectin and oxidative stress [conjugated dienes (CD), homocysteine, total antioxidant capacity, oxidized low-density lipoprotein (OxLDL), OxLDL antibodies, baseline CD of LDL, glutathione (GSH), total glutathione (TGSH), glutathione disulfide], circulation interleukins (IL-6, IL-8), other cytokines [tumor necrosis factor α, monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor], cell adhesion molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, P-selectin, L-selectin), and systemic inflammatory markers [C-reactive protein (CRP), leukocyte count] in separate models were investigated. In age- and sex-adjusted, as well as multivariable-adjusted models, adiponectin was significantly and positively associated with GSH, log TGSH, whereas an inverse association was observed for CD and log EGF. An inverse association between adiponectin and MCP-1, log E-selectin, and log CRP was significant in age- and sex-adjusted models, but not in multivariable-adjusted models. Our results imply that higher levels of adiponectin are associated with a more beneficial oxidative stress profile, with higher levels of principal anti-oxidative GSH and total GSH together with lower levels of lipid peroxidation, possibly through shared pathways. Further studies are needed to investigate whether changes in the oxidative stress profile may be a mechanism linking adiponectin with type 2 diabetes and/or cardiovascular disease. Copyright © 2012 The Obesity Society.

Leptin, adiponectin, leptin to adiponectin ratio and insulin resistance in depressive women.

PubMed

Zeman, Miroslav; Jirak, Roman; Jachymova, Marie; Vecka, Marek; Tvrzicka, Eva; Zak, Ales

2009-01-01

Depressive disorder (DD) is associated with an increased risk of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD). It was suggested, that metabolic syndrome (MetS), cluster of metabolic and hormonal changes, such as insulin resistence (IR), abdominal obesity, dyslipidemia, arterial hypertension and elevated fasting glycaemia, could stand behind the connection. Recent findings have shown, that adipocytokines leptin and adiponectin might play a role in both depression and MetS. The aim of this pilot study was to observe the plasma concentrations of leptin, adiponectin, leptin-to-adiponectin ratio and indices of IR in women with depressive disorder. The plasma leptin, adiponectin, parameters of lipid and glucose homeostasis and indices of IR were investigated in a group of 38 women with DD. The results were compared with those of 38 healthy women of the control group, matched for age. Depressive women differed significantly from the controls in higher concentrations of plasma leptin (p <0.05), insulin (p <0.01), C-peptide (p <0.01), value of HOMA-IR (p <0.01), and the leptin-to-adiponectin ratio (p <0.05).The QUICKI index of insulin sensitivity was lower (p <0.01). HAM-D score of DD cases correlated negatively with adiponectin (r = - 0.3505; p < 0.05), independently of HOMA-IR. We have not found in DD group any differences between the drug free patients and those treated either with escitaloprame alone or in the combination with mirtazapine. The results of the pilot study presented support the hypothesis that at least part of DD cases has increased leptin serum levels and certain features of MetS. It could be the factor connecting depression with an increased risk of either DM2 or CVD.

Adiponectin and resistin gene polymorphisms in association with their respective adipokine levels.

PubMed

Lau, Cia-Hin; Muniandy, Sekaran

2011-05-01

Single nucleotide polymorphisms (SNPs) at the adiponectin and resistin loci are strongly associated with hypoadiponectinemia and hyperresistinemia, which may eventually increase risk of insulin resistance, type 2 diabetes (T2DM), metabolic syndrome (MS), and cardiovascular disease. Real-time PCR was used to genotype SNPs of the adiponectin (SNP+45T>G, SNP+276G>T, SNP+639T>C, and SNP+1212A>G) and resistin (SNP-420C>G and SNP+299G>A) genes in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS) whose ages ranged between 40 and 70 years old. The genotyping results for each SNP marker was verified by sequencing. The anthropometric clinical and metabolic parameters of subjects were recorded. None of these SNPs at the adiponectin and resistin loci were associated with T2DM and MS susceptibility in Malaysian men. SNP+45T>G, SNP+276G>T, and SNP+639T>C of the adiponectin gene did not influence circulating levels of adiponectin. However, the G-allele of SNP+1212A>G at the adiponectin locus was marginally associated (P= 0.0227) with reduced circulating adiponectin levels. SNP-420C>G (df = 2; F= 16.026; P= 1.50×10(-7) ) and SNP+299G>A (df = 2; F= 22.944; P= 2.04×10(-10) ) of the resistin gene were strongly associated with serum resistin levels. Thus, SNP-420C>G and SNP+299G>A of the resistin gene are strongly associated with the risk of hyperresistinemia in Malaysian men. © 2011 The Authors Annals of Human Genetics © 2011 Blackwell Publishing Ltd/University College London.

Short-term effects of fish and fish oil consumption on total and high molecular weight adiponectin levels in overweight and obese adults.

PubMed

Neale, Elizabeth P; Muhlhausler, Beverly; Probst, Yasmine C; Batterham, Marijka J; Fernandez, Francesca; Tapsell, Linda C

2013-05-01

Fish or fish oil consumption may increase levels of total and high molecular weight (HMW) adiponectin, a hormone associated with anti-inflammatory and insulin-sensitising effects, however it is not known if the effects of the food and supplement are the same. The aim of this study was to compare the effect of consuming fish and fish oil supplements on plasma total and HMW adiponectin concentrations in overweight human participants. 29 overweight and obese participants underwent a two week run-in period, followed by a four week isocaloric dietary intervention which provided 1.8 g of long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) in the form of either fish or fish oil supplements. Primary outcomes were changes in plasma total and HMW adiponectin. Secondary outcomes were changes in anthropometric variables, plasma insulin and glucose levels, and dietary intakes. Changes in plasma HMW adiponectin during the intervention period were significantly different between groups (p=0.009). Mean HMW adiponectin increased by 0.29 μg/mL in the 'fish' group and decreased by 0.60 μg/mL in the 'supplement' group. There were no significant changes in other anthropometric and biochemical variables. Dietary data suggested the 'fish' group significantly increased their fish (p=0.001) and dietary LC n-3 PUFA (p=0.001) consumption over the course of the study. Short-term consumption of fish and fish oil supplements did not have the same effects on HMW adiponectin levels. The impact of fish intake on HMW adiponectin levels may not be mediated by its LC n-3 PUFA content alone. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of SCFA on the DNA methylation pattern of adiponectin and resistin in high-fat-diet-induced obese male mice.

PubMed

Lu, Yuanyuan; Fan, Chaonan; Liang, Aimin; Fan, Xiuqin; Wang, Rui; Li, Ping; Qi, Kemin

2018-06-21

Specific adipokines, such as adiponectin and resistin, are secreted from adipose tissue and are associated with the development of obesity. Supplementation of dietary SCFA can prevent and reverse high-fat-diet (HFD)-induced obesity. However, it is not clear whether SCFA ameliorate abnormal expression of adiponectin and resistin in the obese state. The aim of this study was to investigate the effects of SCFA on adiponectin and resistin's expressions in diet-induced obese mice, as well as the potential mechanisms associated with DNA methylation. C57BL/6J male mice were fed for 16 weeks with five types of HFD (34·9 % fat by wt., 60 % kJ) - a control HFD and four HFD with acetate (HFD-A), propionate (HFD-P), butyrate (HFD-B) and their admixture (HFD-SCFA). Meanwhile, a low-fat diet (4·3 % fat by wt., 10 % kJ) was used as the control group. The reduced mRNA levels of adiponectin and resistin in the adipose tissue of the HFD-fed mice were significantly reversed by dietary supplementation of acetate, propionate, butyrate or their admixture to the HFD. Moreover, the expressional changes of adiponectin and resistin induced by SCFA were associated with alterations in DNA methylation at their promoters, which was mediated by reducing the expressions of enzyme-catalysed DNA methyltransferase (DNMT1, 3a, 3b) and the methyl-CpG-binding domain protein 2 (MBD2) and suppressing the binding of these enzymes to the promoters of adiponectin and resistin. Our results indicate that SCFA may correct aberrant expressions of adiponectin and resistin in obesity by epigenetic regulation.

Adiponectin complexes composition in Japanese-Brazilians regarding their glucose tolerance status.

PubMed

Crispim, Felipe; Vendramini, Marcio F; Moisés, Regina S

2013-04-09

Adiponectin circulates in different multimer complexes comprised of low molecular weight trimeric form (LMW), hexamer of middle molecular weight (MMW) and high molecular weight multimers (HMW). In Japanese-Brazilians, a population with high prevalence of glucose metabolism disturbances, we examined the associations of total adiponectin and its multimers with diabetes mellitus. Two study groups were examined: 26 patients with diabetes mellitus (DM,14 women and 12 men, aged 55.3 ± 8.6 years) and 27 age-matched control subjects with normal glucose tolerance (NGT,12 women and 15 men, aged 54.0 ± 9.2 years). We found no significant differences in total [NGT: 6.90 ug/ml (4.38-13.43); DM: 5.38 ug/ml (3.76-8.56), p = 0.35], MMW [NGT:2.34 ug/ml (1.38-3.25); DM: 1.80 ug/ml (1.18-2.84), p = 0.48] or LMW adiponectin [NGT: 2.07 ug/ml (1.45-3.48), DM: 2.93 ug/ml (1.78-3.99), p = 0.32] between groups. In contrast, HMW adiponectin levels were significantly lower in patients with DM [TGN: 2.39 ug/ml (1.20-4.75); DM: 1.04 ug/ml (0.42-1.60), p = 0.001]. A logistic regression analysis was done to identify independent associations with diabetes mellitus. The results showed that HOMA-IR and HMW adiponectin in women were independently associated with diabetes mellitus. The current investigation demonstrates that in Japanese-Brazilians HMW adiponectin is selectively reduced in individuals with type 2 diabetes, while no differences were found in MMW and LMW adiponectin isoforms.

Adiponectin complexes composition in Japanese-Brazilians regarding their glucose tolerance status

PubMed Central

2013-01-01

Background Adiponectin circulates in different multimer complexes comprised of low molecular weight trimeric form (LMW), hexamer of middle molecular weight (MMW) and high molecular weight multimers (HMW). In Japanese-Brazilians, a population with high prevalence of glucose metabolism disturbances, we examined the associations of total adiponectin and its multimers with diabetes mellitus. Methods Two study groups were examined: 26 patients with diabetes mellitus (DM,14 women and 12 men, aged 55.3 ± 8.6 years) and 27 age-matched control subjects with normal glucose tolerance (NGT,12 women and 15 men, aged 54.0 ± 9.2 years). Results We found no significant differences in total [NGT: 6.90 ug/ml (4.38-13.43); DM: 5.38 ug/ml (3.76-8.56), p = 0.35], MMW [NGT:2.34 ug/ml (1.38-3.25); DM: 1.80 ug/ml (1.18-2.84), p = 0.48] or LMW adiponectin [NGT: 2.07 ug/ml (1.45-3.48), DM: 2.93 ug/ml (1.78-3.99), p = 0.32] between groups. In contrast, HMW adiponectin levels were significantly lower in patients with DM [TGN: 2.39 ug/ml (1.20-4.75); DM: 1.04 ug/ml (0.42-1.60), p = 0.001]. A logistic regression analysis was done to identify independent associations with diabetes mellitus. The results showed that HOMA-IR and HMW adiponectin in women were independently associated with diabetes mellitus. Conclusion The current investigation demonstrates that in Japanese-Brazilians HMW adiponectin is selectively reduced in individuals with type 2 diabetes, while no differences were found in MMW and LMW adiponectin isoforms. PMID:23570346

The Impact of CDH13 Polymorphism and Statin Administration on TG/HDL Ratio in Cardiovascular Patients

PubMed Central

Choi, Jung Ran; Kim Yoon, Sungjoo; Park, Jong Keun; Sorn, Sungbin Richard; Park, Mi-Young

2015-01-01

Purpose Adiponectin is expressed in adipose tissue, and is affected by smoking, obesity, and genetic factors, such as CDH13 polymorphism, contributing to the development of coronary vascular diseases (CVDs). Materials and Methods We investigated the effect of genetic variations of CDH13 (rs3865188) on blood chemistry and adiponectin levels in 345 CVD patients undergoing statin-free or statin treatment. Results Genetic variation in CDH13 was significantly correlated with several clinical factors, including adiponectin, diastolic blood pressure, triglyceride (TG), and insulin levels. Subjects with the T allele (mutant form) had significantly lower adiponectin levels than those with the A allele. Total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), TG/high-density lipoprotein cholesterol (HDLc) ratio, and HDL3b subtype were markedly decreased in statin treated subjects regardless of having the A or T allele. TG and TG/HDL in the statin-free group with TT genotype of the rs3865188 was higher than in the others but they were not different in the statin-treated subjects. We observed a significant difference in adiponectin levels between patients with the A and T alleles in the statin-free group; meanwhile, no difference in adiponectin levels was noted in the statin group. Plasma levels of other cytokines, leptin, visfatin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), were not different among the CDH13 genotypes according to statin administration. Body mass index (BMI), TG, insulin, HDL3b, and TG/HDL ratio showed negative correlations with adiponectin levels. Conclusion Plasma adiponectin levels and TG/HDL ratio were significantly different according to variants of CDH13 and statin administration in Korean patients with CVD. PMID:26446643

The Impact of CDH13 Polymorphism and Statin Administration on TG/HDL Ratio in Cardiovascular Patients.

PubMed

Choi, Jung Ran; Jang, Yangsoo; Kim Yoon, Sungjoo; Park, Jong Keun; Sorn, Sungbin Richard; Park, Mi-Young; Lee, Myoungsook

2015-11-01

Adiponectin is expressed in adipose tissue, and is affected by smoking, obesity, and genetic factors, such as CDH13 polymorphism, contributing to the development of coronary vascular diseases (CVDs). We investigated the effect of genetic variations of CDH13 (rs3865188) on blood chemistry and adiponectin levels in 345 CVD patients undergoing statin-free or statin treatment. Genetic variation in CDH13 was significantly correlated with several clinical factors, including adiponectin, diastolic blood pressure, triglyceride (TG), and insulin levels. Subjects with the T allele (mutant form) had significantly lower adiponectin levels than those with the A allele. Total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), TG/high-density lipoprotein cholesterol (HDLc) ratio, and HDL3b subtype were markedly decreased in statin treated subjects regardless of having the A or T allele. TG and TG/HDL in the statin-free group with TT genotype of the rs3865188 was higher than in the others but they were not different in the statin-treated subjects. We observed a significant difference in adiponectin levels between patients with the A and T alleles in the statin-free group; meanwhile, no difference in adiponectin levels was noted in the statin group. Plasma levels of other cytokines, leptin, visfatin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), were not different among the CDH13 genotypes according to statin administration. Body mass index (BMI), TG, insulin, HDL3b, and TG/HDL ratio showed negative correlations with adiponectin levels. Plasma adiponectin levels and TG/HDL ratio were significantly different according to variants of CDH13 and statin administration in Korean patients with CVD.

Effects of sleep restriction on adiponectin levels in healthy men and women.

PubMed

Simpson, Norah S; Banks, Siobhan; Arroyo, Sylmarie; Dinges, David F

2010-12-02

Population studies have consistently found that shorter sleep durations are associated with obesity and cardiovascular disease, particularly among women. Adiponectin is an adipocyte-derived, anti-inflammatory hormone that is related to cardiovascular disease risk. We hypothesized that sleep restriction would reduce adiponectin levels in healthy young adults. 74 healthy adults (57% men, 63% African American, mean age 29.9years) completed 2 nights of baseline sleep at 10h time in bed (TIB) per night followed by 5 nights of sleep restricted to 4h TIB per night. An additional 8 participants were randomized to a control group that received 10h TIB per night throughout the study. Plasma adiponectin levels were measured following the second night of baseline sleep and the fifth night of sleep restriction or control sleep. Sleep restriction resulted in a decrease in plasma adiponectin levels among Caucasian women (Z=-2.19, p=0.028), but an increase among African American women (Z=-2.73, p=0.006). No significant effects of sleep restriction on adiponectin levels were found among men. A 2×2 between-group analysis of covariance on adiponectin change scores controlling for BMI confirmed significant interactions between sleep restriction and race/ethnicity [F(1,66)=13.73, p<0.001], as well as among sleep restriction, race/ethnicity and sex [F(1,66)=4.27, p=0.043)]. Inflammatory responses to sleep loss appear to be moderated by sex and race/ethnicity; observed decreases in adiponectin following sleep restriction may be one avenue by which reduced sleep duration promotes cardiovascular risk in Caucasian women. Copyright © 2010 Elsevier Inc. All rights reserved.

Plasma adiponectin and depressive symptoms during pregnancy and the postpartum period: A prospective cohort study.

PubMed

Rebelo, Fernanda; Farias, Dayana R; Struchiner, Claudio J; Kac, Gilberto

2016-04-01

Some authors have described an inverse association between adiponectin and depression, but this association has not yet been investigated during the perinatal period. To evaluate the association between the plasma adiponectin levels and symptoms of depression in women from early pregnancy to 30-45 days postpartum. A prospective cohort of 235 women was analyzed, with four waves of follow-up: 5-13th, 22-26th, and 30-36th gestational weeks and 30-45 days postpartum. Depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS; cutoff ≥ 11). The plasma adiponectin concentrations were measured using an enzyme-linked immunosorbent assay. The statistical analyses included linear mixed effects regressions to model the association between these time-dependent variables. The prevalence of depressive symptoms was 35.5%, 22.8%, 21.8%, and 16.9% and the median (µg/mL) adiponectin levels were 4.8, 4.7, 4.4, and 7.5 in the 1st, 2nd, and 3rd trimesters and the postpartum period, respectively. Women who remained non-depressed throughout the study tended to have higher values of adiponectin throughout pregnancy and the postpartum period compared to those who had depressive symptoms at least once, but this difference was not statistically significant (β=-0.14; p=0.071). There was no statistically significant association between the plasma adiponectin levels and the EPDS scores in the multiple model (β=-0.07; p=0.320). Losses to follow-up, different procedures for the blood draws at the prenatal and postpartum visits, and the presence of a nested clinical trial with omega-3 supplementation. The plasma adiponectin levels were not associated with depressive symptoms during the perinatal period. Copyright © 2016 Elsevier B.V. All rights reserved.

Dietary Japanese millet protein ameliorates plasma levels of adiponectin, glucose, and lipids in type 2 diabetic mice.

PubMed

Nishizawa, Naoyuki; Togawa, Tubasa; Park, Kyung-Ok; Sato, Daiki; Miyakoshi, Yo; Inagaki, Kazuya; Ohmori, Norimasa; Ito, Yoshiaki; Nagasawa, Takashi

2009-02-01

Millet is an important food crop in Asia and Africa, but the health benefits of dietary millet are little known. This study defined the effects of dietary Japanese millet on diabetic mice. Feeding of a high-fat diet containing Japanese millet protein concentrate (JMP, 20% protein) to type 2 diabetic mice for 3 weeks significantly increased plasma levels of adiponectin and high-density lipoprotein cholesterol (HDL cholesterol) and decreased the levels of glucose and triglyceride as compared to control. The starch fraction of Japanese millet had no effect on glucose or adiponectin levels, but the prolamin fraction beneficially modulated plasma glucose and insulin concentrations as well as adiponectin and tumor necrosis factor-alpha gene expression. Considering the physiological significance of adiponectin and HDL cholesterol levels in type 2 diabetes, insulin resistance, and cardiovascular disease, our findings imply that dietary JMP has the potential to ameliorate these diseases.

Elevated Adiponectin Antibody Levels in Sera of Patients with Atherosclerosis-Related Coronary Artery Disease, Cerebral Infarction and Diabetes Mellitus

PubMed Central

Hiwasa, Takaki; Zhang, Xiao-Meng; Kimura, Risa; Ohno, Mikiko; Chen, Po-Min; Nishi, Eiichiro; Ono, Koh; Kimura, Takeshi; Kamitsukasa, Ikuo; Wada, Takeshi; Aotsuka, Akiyo; Mine, Seiichiro; Takizawa, Hirotaka; Kashiwado, Koichi; Takemoto, Minoru; Kobayashi, Kazuki; Kawamura, Harukiyo; Ishibashi, Ryoichi; Yokote, Koutaro; Nakamura, Rika; Tomiyoshi, Go; Shinmen, Natsuko; Kuroda, Hideyuki

2016-01-01

Adiponectin secreted from the adipocytes plays pleiotropic, anti-atherosclerotic roles, such as enhancement of insulin secretion and an increase in energy expenditure. The measurement of levels of circulating adiponectin is useful to evaluate the progression of atherosclerosis-related diseases, such as coronary artery disease (CAD), cerebral infarction (CI) and diabetes mellitus (DM). We examined the serum antibody levels against recombinant adiponectin protein via the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) method. The results revealed that the antibody levels were significantly higher in patients with CAD, CI and type 2 DM, than in healthy donors. Receiver operating curve analysis showed that the sensitivity was in a range of 41–48% for CAD, CI and DM. Thus, the serum anti-adiponectin antibody levels could be a common marker for atherosclerosis-related diseases. PMID:28936256

Effect of anti-TNF treatment on body composition and serum adiponectin levels of women with rheumatoid arthritis.

PubMed

Serelis, John; Kontogianni, Meropi D; Katsiougiannis, Stergios; Bletsa, Maria; Tektonidou, Maria G; Skopouli, Fotini N

2008-06-01

The aim of this study was to investigate the effect of anti-tumor necrosis factor alpha (anti-TNF) treatment on body composition and serum adiponectin levels of women with rheumatoid arthritis (RA). Nineteen women with RA starting anti-TNF treatment were included in the study. Disease activity, body composition, lumbar spine bone mineral density (BMD) and serum adiponectin concentrations were measured at baseline and after 1 year of follow-up. No important changes on body composition and lumbar spine BMD were observed, while the serum levels of adiponectin levels increased after 1 year of anti-TNF treatment (p = 0.02). Anti-TNF treatment in women with RA does not have any significant effect on body composition; however, it is associated with increase in adiponectin levels which may ameliorate the systemic inflammatory response state associated with RA.

Effects of febuxostat on platelet-derived microparticles and adiponectin in patients with hyperuricemia.

PubMed

Nishizawa, Tohru; Taniura, Takehito; Nomura, Shosaku

2015-12-01

Platelet-derived microparticles (PDMPs) and adiponectin play an important role in the development of atherothrombosis. We investigated the effect of febuxostat on circulating PDMP levels and adiponectin in hyperuricemic patients. Levels of PDMP and biomarkers were measured using an ELISA at baseline and after 2 and 6 months of treatment. Plasma levels of PDMPs and biomarkers were higher, while those of adiponectin were lower in hyperuricemic patients than in normouricemic controls. Uric acid and interleukin (IL)-6 levels decreased significantly in hyperuricemic patients after 2 months of febuxostat treatment. However, PDMP and biomarkers decreased significantly in hyperuricemic patients after only 6 months of febuxostat treatment and adiponectin increased significantly. These results suggest that the effects of febuxostat for PDMPs seen may be the effect on xanthine oxidase but not the decrease of uric acid, and febuxostat may be beneficial for primary prevention of atherothrombosis in hyperuricemic patients.

Effects of febuxostat on platelet-derived microparticles and adiponectin in patients with hyperuricema

PubMed Central

Nishizawa, Tohru; Taniura, Takehito; Nomura, Shosaku

2015-01-01

Platelet-derived microparticles (PDMPs) and adiponectin play an important role in the development of atherothrombosis. We investigated the effect of febuxostat on circulating PDMP levels and adiponectin in hyperuricemic patients. Levels of PDMP and biomarkers were measured using an ELISA at baseline and after 2 and 6 months of treatment. Plasma levels of PDMPs and biomarkers were higher, while those of adiponectin were lower in hyperuricemic patients than in normouricemic controls. Uric acid and interleukin (IL)-6 levels decreased significantly in hyperuricemic patients after 2 months of febuxostat treatment. However, PDMP and biomarkers decreased significantly in hyperuricemic patients after only 6 months of febuxostat treatment and adiponectin increased significantly. These results suggest that the effects of febuxostat for PDMPs seen may be the effect on xanthine oxidase but not the decrease of uric acid, and febuxostat may be beneficial for primary prevention of atherothrombosis in hyperuricemic patients. PMID:26164850

An In Vivo Screen of Secreted Proteins Identifies Adiponectin as a Regulator of Murine Cutaneous Wound Healing

PubMed Central

Salathia, Neeraj S; Shi, Jian; Zhang, Jay; Glynne, Richard J

2013-01-01

Skin wounds comprise a serious medical issue for which few pharmacological interventions are available. Moreover, the inflammatory, angiogenic, and proliferative facets of a typical response to a wound each have broader relevance in other pathological conditions. Here we describe a genomics-driven approach to identify secreted proteins that modulate wound healing in a mouse ear punch model. We show that adiponectin, when injected into the wound edge, accelerates wound healing. Notably, adiponectin injection causes upregulation of keratin gene transcripts within hours of treatment, and subsequently promotes collagen organization, formation of pilosebaceous units, and proliferation of cells in the basal epithelial cell layer and pilosebaceous units of healing tissue. The globular domain of adiponectin is sufficient to mediate accelerated dorsal skin wound closure, and the effects are lost in mice that are homozygous null for the adiponectin receptor 1 gene. These findings extend recent observations of a protective role of adiponectin in other tissue injury settings, suggest modulation of AdipoR1 for the clinical management of wounds, and demonstrate a new approach to the identification of regulators of a wound healing response. PMID:23096717

Association between carotid intima-media thickness and adiponectin in participants without diabetes or cardiovascular disease of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

PubMed

de Almeida-Pititto, Bianca; Ribeiro-Filho, Fernando Flexa; Santos, Itamar S; Lotufo, Paulo A; Bensenor, Isabela M; Ferreira, Sandra Rg

2017-01-01

Objective The study assessed the association of adiponectin concentration with carotid intima-media thickness (CIMT) in middle-aged participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) without diabetes or cardiovascular disease. Design Cross-sectional analyses. Methods A sample of 687 individuals (35-54 years old) without diabetes or cardiovascular disease was stratified into two categories according to CIMT (< or ≥ 75th percentile). Traditional risk factors, C-reactive protein and adiponectin values were compared between categories by Student's t-test and frequencies by chi-square test. In linear regression models, associations of CIMT with adiponectin, adjusted for adiposity, blood pressure, C-reactive protein and homeostasis model assessment-insulin resistance were tested. Mean CIMT values were compared across quartiles of adiponectin concentrations using analysis of variance. Results Three hundred and forty-one individuals (49.6%) were women and 130 (19.0%) had three traditional cardiovascular risk factors. Those with elevated CIMT (21.8%) had greater mean values of body mass index (26.2(3.8) vs. 27.7(4.0)kg/m 2 , p < 0.001), waist circumference (86.9(10.1) vs. 90.1(10.8) cm, p = 0.001), systolic blood pressure (116.2(13.6) vs.121.2(16.1) mmHg, p < 0.001), homeostasis model assessment index (1.4(0.9-2.4) vs. 1.8(1.1-2.9), p = 0.011), C-reactive protein (1.2 (0.6-2.6) vs. 1.4(0.8-3.2) mg/l, p = 0.054) and adiponectin (9.9 (6.0-14.7) vs. 8.9 (5.3-13.8) µg/ml, p = 0.002) levels than the counterpart, while plasma glucose and lipids were not different between groups. In the adjusted model, blood pressure (directly) and adiponectin (inversely) persisted associated with high CIMT. Mean CIMT was greater in the first quartile of adiponectin when compared with the other three quartiles ( p = 0.019). Conclusions Lower adiponectin levels together with higher blood pressure were independently associated with elevated CIMT. Adiponectin concentration may be an independent marker of early structural damage in individuals at low-to-moderate cardiovascular risk.

The concentrations of adipokines in goat milk: relation to plasma levels, inflammatory status, milk quality and composition.

PubMed

Guzel, Saime; Yibar, Artun; Belenli, Deniz; Cetin, Ismail; Tanriverdi, Meltem

2017-03-23

The main objectives of our study were to measure the major adipokines adiponectin, leptin and resistin in goat milk, to assess their interrelationships and to assess their relationships with the plasma and serum concentrations of total protein, cholesterol, total lipids, plasma C-reactive protein (CRP), milk somatic cell count (SCC), milk total aerobic colony and lactobacillus count, and milk components in lactating Saanen goats. The study was performed on eighteen lactating Saanen goats. Milk and blood samples were collected on days 20, 35, 50, 65 and 80 of lactation postpartum. The milk and plasma adiponectin levels on days 50, 65 and 80 postpartum were significantly higher than those on day 20. The milk and plasma leptin levels were lower on day 20 than on days 35, 50, 65 and 80. The milk concentrations of these major adipokines were positively intercorrelated. The milk and plasma concentrations of these three adipokines were also positively correlated. The plasma CRP concentrations correlated positively with milk leptin and resistin concentrations and inversely with milk adiponectin concentration. Milk adiponectin concentration was inversely related with its SCC. These data confirm that adiponectin, leptin and resistin are present in goat milk. The milk concentrations of these three adipokines were interrelated and interacted with the general inflammatory marker, CRP. The inverse relationship between milk adiponectin concentrations and its SCC suggests that variations in milk adiponectin might be involved in the udder health of lactating goats, but clinical trials are needed to support this hypothesis.

Developmental programming: effect of prenatal steroid excess on intraovarian components of insulin signaling pathway and related proteins in sheep.

PubMed

Ortega, Hugo H; Rey, Florencia; Velazquez, Melisa M L; Padmanabhan, Vasantha

2010-06-01

Prenatal testosterone (T) excess increases ovarian follicular recruitment, follicular persistence, insulin resistance, and compensatory hyperinsulinemia. Considering the importance of insulin in ovarian physiology, in this study, using prenatal T- and dihydrotestosterone (DHT, a nonaromatizable androgen)-treated female sheep, we tested the hypothesis that prenatal androgen excess alters the intraovarian insulin signaling cascade and metabolic mediators that have an impact on insulin signaling. Changes in ovarian insulin receptor (INSRB), insulin receptor substrate 1 (IRS1), mammalian target of rapamycin (MTOR), phosphatidylinositol 3-kinase (PIK3), peroxisome proliferator-activated receptor-gamma (PPARG), and adiponectin proteins were determined at fetal (Days 90 and 140), postpubertal (10 mo), and adult (21 mo) ages by immunohistochemistry. Results indicated that these proteins were expressed in granulosa, theca, and stromal compartments, with INSRB, IRS1, PPARG, and adiponectin increasing in parallel with advanced follicular differentiation. Importantly, prenatal T excess induced age-specific changes in PPARG and adiponectin expression, with increased PPARG expression evident during fetal life and decreased antral follicular adiponectin expression during adult life. Comparison of developmental changes in prenatal T and DHT-treated females found that the effects on PPARG were programmed by androgenic actions of T, whereas the effects on adiponectin were likely by its estrogenic action. These results suggest a role for PPARG in the programming of ovarian disruptions by prenatal T excess, including a decrease in antral follicular adiponectin expression and a contributory role for adiponectin in follicular persistence and ovulatory failure.

PI3K-resistant GSK3 controls adiponectin formation and protects from metabolic syndrome.

PubMed

Chen, Hong; Fajol, Abul; Hoene, Miriam; Zhang, Bingbing; Schleicher, Erwin D; Lin, Yun; Calaminus, Carsten; Pichler, Bernd J; Weigert, Cora; Häring, Hans U; Lang, Florian; Föller, Michael

2016-05-17

Metabolic syndrome is characterized by insulin resistance, obesity, and dyslipidemia. It is the consequence of an imbalance between caloric intake and energy consumption. Adiponectin protects against metabolic syndrome. Insulin-induced signaling includes activation of PI3 kinase and protein kinase B (PKB)/Akt. PKB/Akt in turn inactivates glycogen synthase kinase (GSK) 3, a major regulator of metabolism. Here, we studied the significance of PI3K-dependent GSK3 inactivation for adiponectin formation in diet-induced metabolic syndrome. Mice expressing PI3K-insensitive GSK3 (gsk3(KI)) and wild-type mice (gsk3(WT)) were fed a high-fat diet. Compared with gsk3(WT) mice, gsk3(KI) mice were protected against the development of metabolic syndrome as evident from a markedly lower weight gain, lower total body and liver fat accumulation, better glucose tolerance, stronger hepatic insulin-dependent PKB/Akt phosphorylation, lower serum insulin, cholesterol, and triglyceride levels, as well as higher energy expenditure. Serum adiponectin concentration and the activity of transcription factor C/EBPα controlling the expression of adiponectin in adipose tissue was significantly higher in gsk3(KI) mice than in gsk3(WT) mice. Treatment with GSK3 inhibitor lithium significantly decreased the serum adiponectin concentration of gsk3(KI) mice and abrogated the difference in C/EBPα activity between the genotypes. Taken together, our data demonstrate that the expression of PI3K-insensitive GSK3 stimulates the production of adiponectin and protects from diet-induced metabolic syndrome.

Adiponectin and waist circumference as predictors of insulin-resistance in women.

PubMed

Bonneau, Graciela A; Pedrozo, Williams R; Berg, Gabriela

2014-01-01

The initial disturbance of insulin resistance seems to focus on adipose tissue is a dynamic organ involved in many physiological and metabolic processes. Expresses and secretes a variety of active peptides, adipocytokines. To evaluate the prevalence of insulin-resistance in an healthy urban middle age population and to explore the role of adiponectin, inflammatory biomarkers (hs-CRP) and traditional cardiovascular risk factors as predictors of the insulin-resistance state. We studied of 176 participants (117 women and 59 men, 25-74 years), individuals with diabetes, hypothyroidism or hyperthyroidism, infectious disease, renal, or hepatic neoplasms and pregnant women were excluded. We evaluated glucose, insulin, adiponectin and hs-CRP. We found that 17.2% of individuals presented insulin-resistance. Correlation was found between waist circumference, body mass index, blood pressure and HOMA index (p<0.01). Adiponectin was associated with the insulin-resistance (p<0.001) but not hs-CRP. Adiponectin (β=0.385, p=0.004) and waist circumference (β=0.116, p=0.02) were predictors of IR only in women, meanwhile none of the analyzed biomarkers predicted insulin-resistance in men. Besides, postmenopausal women presented higher adiponectin levels than premenopausal 7.63 (4.46-9.58) vs 5.50 (3.83-7.40) μg/ml, p=0.01. Adiponectin and waist circumference are important predictors of insulin-resistance even in healthy non-diabetic women, they may open a new opportunity to improve current risk estimation. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Dietary factors associated with subclinical inflammation among girls.

PubMed

Del Mar Bibiloni, M; Maffeis, C; Llompart, I; Pons, A; Tur, J A

2013-12-01

Dietary patterns and biomarkers of inflammation have been scarcely associated. The aim was to assess dietary factors associated with subclinical inflammation among girls. Fasting blood samples were collected from 12- to 17-year old girls (n=219) to measure adiponectin, leptin, tumor necrosis factor-alpha, plasminogen activator inhibitor 1 (PAI-1), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) levels. Body mass index (BMI) and waist-to-height ratio (WHtR), and food intake were also measured. Western (WDP) and Mediterranean (MDP) dietary patterns were identified. BMI and WHtR were associated with adiponectin, leptin and hs-CRP (the last, only associated with BMI). Intakes of β-carotene equivalents and vitamin C were associated with adiponectin; saturated fatty acids (SFA), vitamin A, manganese and selenium with leptin; linoleic acid with PAI-1; and oleic acid and vitamin E with IL-6. Selenium was inversely associated with adiponectin, whereas magnesium was positively associated with IL-6. MDP was associated with higher plasma concentrations of adiponectin (β=0.174, P<0.05); after adjustment for BMI, associations were not significant (β=0.144, P=0.076). WDP was negatively associated with adiponectin (β=-0.177, P<0.05) and positively with IL-6 (β=0.183, P<0.05). Subclinical inflammation is detectable with increasing BMI and also WHtR. Measures of adiposity (BMI and WHtR) are significant predictors of adiponectin, leptin and hs-CRP. Dietary patterns per se have a small role in affecting inflammatory markers among adolescents.

Plasma adiponectin levels and incident glucose intolerance in Japanese-Brazilians: a seven-year follow-up study.

PubMed

Vendramini, Marcio F; Ferreira, Sandra R G; Gimeno, Suely G A; Kasamatsu, Teresa S; Miranda, Walkiria L; Moisés, Regina S

2006-09-01

The objective of this study was to investigate whether decreased baseline adiponectin levels are an independent risk factor for development of glucose intolerance in a population-based study of Japanese-Brazilians, a group with one of the highest prevalence rates of diabetes worldwide. We examined 210 Japanese-Brazilians (97 male and 113 female, aged 56.7+/-10.1 years) with normal glucose tolerance (NGT). Plasma adiponectin, insulin, fasting and 2-h plasma glucose and lipid profile were evaluated at baseline and also at 7-year follow-up. Plasma adiponectin levels were significantly lower in glucose intolerance progressors compared with subjects who remained NGT. By increasing tertiles of adiponectin, the frequencies of subjects who progressed to glucose intolerance were 40%, 33% and 27% and the frequencies of subjects who remained NGT were 13%, 35% and 52% (chi2=15.8, p=0.001). Logistic regression analyses showed that adiponectin levels (OR for the highest versus lowest tertile: 0.31; 95% CI: 0.12-0.84, p=0.021), male sex (OR: 2.61, 95% CI: 1.21-5.65, p=0.015), fasting plasma glucose (0R: 3.05, 95% CI: 1.35-6.91, p=0.008) and waist circumference (OR: 1.04, 95% CI: 1.00-1.08, p=0.046) were independent risk factors for the progression to glucose intolerance. In conclusion, low plasma levels of adiponectin is one of several independent predictors of glucose intolerance in a Japanese-Brazilian population.

High Fiber and Low Starch Intakes Are Associated with Circulating Intermediate Biomarkers of Type 2 Diabetes among Women.

PubMed

AlEssa, Hala B; Ley, Sylvia H; Rosner, Bernard; Malik, Vasanti S; Willett, Walter C; Campos, Hannia; Hu, Frank B

2016-02-01

Carbohydrate quality has been consistently related to the risk of type 2 diabetes (T2D). However, limited information is available about the effect of carbohydrate quality on biomarkers related to T2D. We examined the associations of carbohydrate quality measures (CQMs) including carbohydrate intake; starch intake; glycemic index; glycemic load; total, cereal, fruit, and vegetable fiber intakes; and different combinations of these nutrients with plasma concentrations of adiponectin, C-reactive protein (CRP), and glycated hemoglobin (HbA1c). This is a cross-sectional analysis of 2458 diabetes-free women, ages 43-70 y, in the Nurses Health Study. CQMs were estimated from food-frequency questionnaires, and averages from 1984, 1986, and 1990 were used. Plasma biomarkers were collected in 1990. Multiple linear regression models were used to assess the associations between CQMs and biomarkers. After age, body mass index, lifestyle, and dietary variables were adjusted, 1) total fiber intake was positively associated with adiponectin (P-trend = 0.004); 2) cereal fiber intake was positively associated with adiponectin and inversely associated with CRP, and fruit fiber intake was negatively associated with HbA1c concentrations (all P-trend < 0.03); 3) starch intake was inversely associated with adiponectin (P-trend = 0.02); 4) a higher glycemic index was associated with lower adiponectin and higher HbA1c (both P-trend < 0.05); 5) a higher carbohydrate-to-total fiber intake ratio was associated with lower adiponectin (P-trend = 0.005); 6) a higher starch-to-total fiber intake ratio was associated with lower adiponectin and higher HbA1c (both P-trend < 0.05); and 7) a higher starch-to-cereal fiber intake ratio was associated with lower adiponectin (P-trend = 0.002). A greater fiber intake and a lower starch-to-fiber intake ratio are favorably associated with adiponectin and HbA1c, but only cereal fiber intake was associated with CRP in women. Further research is warranted to understand the potential mechanism of these associations in early progression of T2D. © 2016 American Society for Nutrition.

Short communication: The association of adiponectin and leptin concentrations with prepartum dietary energy supply, parity, body condition, and postpartum hyperketonemia in transition dairy cows.

PubMed

Mann, S; Urh, C; Sauerwein, H; Wakshlag, J J; Yepes, F A Leal; Overton, T R; Nydam, D V

2018-01-01

Adipokines-hormones produced by adipose tissue-have important regulatory functions, and their concentrations can change around the time of calving when energy balance rapidly decreases. Hence, energy balance may be an important factor in determining the circulating concentrations of adipokines, particularly adiponectin and leptin. The objective of our study was to investigate the association between the level of energy fed to prepartum Holstein cows and circulating concentrations of adiponectin and leptin before and after calving. Holstein dairy cows entering second or greater lactation were fed either a controlled-energy diet formulated to supply approximately 100% of energy requirements (n = 28) or a high-energy diet formulated to supply approximately 150% of energy requirements throughout the entire dry period (n = 28). Serum samples were analyzed for adiponectin and leptin concentrations at 56, 28, 10, and 1 d prepartum as well as on d 1, 10, 21, and 42 postpartum using ELISA. Parity was dichotomized into cows entering second versus higher parity. Average peripartum body condition score (BCS) was computed from weekly measurements and dichotomized into animals with an average BCS of ≤3.25 and >3.25. In addition, cows were classified according to the occurrence of hyperketonemia (β-hydroxybutyrate concentrations ≥1.2 mmol/L at any time between 3 and 21 d in milk). Data were analyzed using repeated-measures ANOVA. Serum leptin but not adiponectin concentrations were associated with prepartum feeding level such that leptin concentrations increased transiently during the dry period in cows overfed energy, but concentrations were not different postpartum. Cows entering second parity had higher adiponectin and lower leptin concentrations compared with cows in higher parities. Cows that developed hyperketonemia postpartum had consistently lower adiponectin concentrations during the study period. Cows with average BCS >3.25 had higher leptin concentrations during the dry period only, but adiponectin concentrations were not associated with BCS. In conclusion, prepartum energy level had only transient effects on leptin concentrations and did not lead to changes in adiponectin concentrations. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Globular adiponectin ameliorates metabolic insulin resistance via AMPK-mediated restoration of microvascular insulin responses

PubMed Central

Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

2015-01-01

Abstract Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance, and microvasculature plays a critical role in the regulation of insulin action in muscle. Here we tested whether adiponectin replenishment could improve metabolic insulin sensitivity in male rats fed a high-fat diet (HFD) via the modulation of microvascular insulin responses. Male Sprague–Dawley rats were fed either a HFD or low-fat diet (LFD) for 4 weeks. Small resistance artery myograph changes in tension, muscle microvascular recruitment and metabolic response to insulin were determined. Compared with rats fed a LFD, HFD feeding abolished the vasodilatory actions of globular adiponectin (gAd) and insulin on pre-constricted distal saphenous arteries. Pretreatment with gAd improved insulin responses in arterioles isolated from HFD rats, which was blocked by AMP-activated protein kinase (AMPK) inhibition. Similarly, HFD abolished microvascular responses to either gAd or insulin and decreased insulin-stimulated glucose disposal by ∼60%. However, supplementing gAd fully rescued insulin’s microvascular action and significantly improved the metabolic responses to insulin in HFD male rats and these actions were abolished by inhibition of either AMPK or nitric oxide production. We conclude that HFD induces vascular adiponectin and insulin resistance but gAd administration can restore vascular insulin responses and improve insulin’s metabolic action via an AMPK- and nitric oxide-dependent mechanism in male rats. Key points Adiponectin is an adipokine with anti-inflammatory and anti-diabetic properties. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance in obesity and diabetes. Insulin resistance is present in muscle microvasculature and this may contribute to decreased insulin delivery to, and action in, muscle. In this study we examined whether adiponectin ameliorates metabolic insulin resistance by affecting muscle microvascular recruitment. We demonstrated that a high-fat diet induces vascular adiponectin and insulin resistance but globular adiponectin administration can restore vascular insulin responses and improve insulin’s metabolic action via an AMPK- and nitric oxide-dependent mechanism. This suggests that globular adiponectin might have a therapeutic potential for improving insulin resistance and preventing cardiovascular complications in patients with diabetes via modulation of microvascular insulin responses. PMID:26108677

Adiponectin and pro-inflammatory cytokines are modulated in Vietnamese patients with type 2 diabetes mellitus.

PubMed

Tong, Hoang Van; Luu, Nguyen Kim; Son, Ho Anh; Hoan, Nguyen Van; Hung, Trinh Thanh; Velavan, Thirumalaisamy P; Toan, Nguyen Linh

2017-05-01

Adipose tissue-derived hormones are associated with metabolic disorders including type 2 diabetes mellitus. The present study investigated the levels of adiponectin and pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β) and IL-10 in Vietnamese patients with type 2 diabetes mellitus, and their correlations with clinical parameters of overweight and type 2 diabetes mellitus. Based on body mass index, 73 patients with type 2 diabetes mellitus were categorized either as overweight or non-overweight. As healthy controls, 57 overweight and non-overweight individuals without type 2 diabetes mellitus were included. The adiponectin, TNF-α, IL-1β and IL-10 levels were measured in the sera samples in all study participants by enzyme-linked immunosorbent assay and were correlated with clinical parameters. The adiponectin levels were lower in patients with type 2 diabetes mellitus (2.5 ± 1.5 μg/mL) compared with controls (16 ± 18.6 μg/mL; P < 0.0001), and were decreased in overweight individuals compared with those who were not overweight. The TNF-α and IL-1β levels were increased, whereas the IL-10 levels were decreased in patients with type 2 diabetes mellitus and in overweight controls compared with non-overweight controls (P < 0.0001). The adiponectin levels were correlated with the TNF-α, IL-1β, IL-10 levels, and the clinical parameters of overweight and type 2 diabetes mellitus. The quantitative insulin sensitivity check index and homeostasis model assessment insulin resistance indexes were correlated with the relative ratios of adiponectin/TNF-α, adiponectin/IL-1β, adiponectin/IL-10, TNF-α/IL-10 and IL-1β/IL-10. Adiponectin and pro-inflammatory cytokines are associated with type 2 diabetes mellitus, and might serve as a prognostic marker and a therapeutic intervention for overweight-related type 2 diabetes mellitus. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Predict value of adiponectin for coronary atherosclerosis plaques according to computed tomography angiography in an asymptomatic population.

PubMed

Gan, Lu; Yang, Li; Yan, Guangtao

2018-05-25

The association between serum adiponectin levels and coronary atherosclerosis plaque characteristics in asymptomatic populations is unclear. To examine the predictive value of serum adiponectin levels for coronary high risk plaques as detected by computed tomography angiography (CTA). This was a cross-sectional study. All patients were divided into high risk plaque group and non high risk plaque group. The FRS was calculated for each patient. CTA was performed for each patient. Adiponectin levels were measured by flow fluorescence immunmicrobead assay (FFIA). Receiver-operating characteristic (ROC) curves and multivariate analysis was used to determine the predictive value of adiponectin for high risk plaques. The high risk plaque group showed lower adiponectin levels than non high risk plaque group (median, 7.27 vs. 8.51 μg/ml, P = 0.003). The multivariate analysis showed that age (OR = 2.62, 95%CI: 1.51-4.56, P = 0.001), hyperlipidemia (OR = 1.89, 95%CI: 1.07-3.36, P = 0.029), high-density lipoprotein cholesterol (HDL-C) (OR = 0.46, 95%CI: 0.24-0.87, P = 0.02), the ratio of total cholesterol to high-density lipoproteincholesterol (TC/HDL-C) (OR = 0.69, 95%CI: 0.50-0.94, P = 0.02), apolipoprotein B (apoB) (OR = 3.08, 95%CI: 1.50-6.32, P = 0.002), and adiponectin (OR = 0.37, 95%CI: 0.19-0.74, P = 0.005) were independently associated with the presence of high risk plaques. AUC of the multivariate model for high-risk plaques was 0.728 (95%CI: 0.627-0.783). Sensitivity was 74.9%, specificity was 60.2%, the positive predictive value was 65.3%, and the negative predictive value was 70.6%. Decreased adiponectin levels were associated with the presence of high-risk plaques in asymptomatic populations at low to intermediate FRS. Adiponectin can play an important role in plaque screening before coronary CTA. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of berberine on the ratio of high-molecular weight adiponectin to total adiponectin and adiponectin receptors expressions in high-fat diet fed rats.

PubMed

Wu, Yue-Yue; Zha, Ying; Liu, Jun; Wang, Fang; Xu, Jiong; Chen, Zao-Ping; Ding, He-Yuan; Sheng, Li; Han, Xiao-Jie

2016-11-17

To assess the effects of berberine (BBR) on high-molecular weight (HMW) adiponectin and adiponectin receptors (adipoR1/adipoR2) expressions in high-fat (HF) diet fed rats. Forty Wistar male rats were randomly assigned into a normal diet fed group and three HF diet (fat for 45% calories) fed groups (n=10 for each group). All rats underwent 12 weeks of feeding. After 4 weeks feeding, rats in the two of three HF diet fed groups were treated with 150 mg·kg -1 ·day -1 BBR (HF+LBBR group) and 380 mg·kg -1 ·day -1 BBR (HF+HBBR group) by gavage once a day respectively for the next 8 weeks while the rats in other groups treated with vehicle (NF+Veh and HF+Veh). Body weight and food intake were observed and recorded on daily basis. At the end of 12 weeks, the blood, liver, epididymal fat tissues and quadriceps femoris muscles were collected. Fasting insulin, plasma fasting glucose, serum free fatty acid (FFA), total adiponectin and HMW adiponectin levels were measured by enzyme linked immunosorbent assay method. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine the insulinsensitizing. Meanwhile the homeostasis model assessment (HOMA) method was used to determine insulin resistance (HOMA-IR). The expressions of adipoR1, adipoR2 and adenosine monophophate activated protein kinase (AMPK) phosphorylation level in skeletal muscle and liver tissue were detected by Western blot. Liver and kidney toxicity were evaluated during treatment. The body weight of rats in high- or low-dose BBR group reduced as well as HOMA-IR, FFA concentrations and fasting insulin levels decreased compared with HF+Veh group (P<0.05). BBR also increased the ratio of HMW to total adiponectin in high fat-fed rats compared with rats in the HF+Veh group. High- and low-dose BBR increased adipoR1 expression in skeletal muscle by over 6- and 2-fold (P<0.05), respectively, and high-dose BBR also increased adipoR2 expression in liver tissue by over 2-fold (P<0.05). BBR significantly increased AMPK phosphorylation in HF diet rats compared with normal diet rats (P<0.05). The ratio of HMW to total adiponectin was inversely correlated with HOMA-IR (r=-0.52, P=0.001). Meantime, no liver and kidney toxicity was found in high fat-fed rats that treated by BBR. Berberine may improve insulin resistance by increasing the expression of adiponectin receptors and the ratio of HMW to total adiponectin.

Adiponectin gene polymorphisms: Association with childhood obesity

PubMed Central

Fraga, Vanêssa Gomes; Gomes, Karina Braga

2014-01-01

The current childhood obesity epidemic represents a particular challenge for public health. Understanding of the etiological mechanisms of obesity remains integral in treating this complex disorder. In recent years, studies have elucidated the influence of hormones secreted by adipose tissue named adipokines. Adiponectin is a adipokine that exhibits important anti-inflammatory, insulin-sensitizing and anti-atherogenic properties and it is strongly associated to obesity development. It is well known that adiponectin levels decrease with obesity. Furthermore, studies show that some single nucleotide polymorphisms in the gene encoding adiponectin, ADIPOQ, may influence the expression of this protein. The objective of this paper is to provide an up-to-date review of ADIPOQ polymorphisms in the context of childhood obesity. PMID:27625863

Effects of Simvastatin Treatment on Serum Adiponectin Concentrations in Patients With Dislipidemia

PubMed Central

Moezzi, Atefeh; Parizadeh, Seyyed Mohammad Reza; Tavallaie, Shima; Mazidi, Mohsen; Afzali, Fariba; Adab, Afrouz; Ferns, Gordon; Ghayour Mobarhan, Majid

2014-01-01

Background: Adiponectin is an adipose tissue-derived protein with anti-inflammatory properties. Statins are a class of cholesterol-lowering drugs, widely used for treatment of cardiovascular diseases. Objectives: In the current study, we aimed to assess the effects of simvastatin on serum levels of adiponectin in patients with dyslipidemia, recruited from Ghaem Hospital, Mashhad, Iran. Materials and Methods: A total of 102 patients with dyslipidemia were treated with simvastatin or placebo during a double-blind, cross-over, placebo-controlled trial. The adiponectin levels were measured before and after each treatment period. Seventy seven participants completed the study. Results: There was a significant reduction in serum total cholesterol (approxmately 21%), low density lipoprotein-cholesterol (LDL-C) (approxmately 28%), and triglycerides (approxmately 11%), after four weeks of treatment with simvastatin (P < 0.001). Conclusions: No significant change in serum adiponectin concentrations was observed after treatment with simvastatin. This may be because of the relatively short duration of treatment and longer treatment duration may be necessary to investigation in future studies. PMID:25389496

Effects of simvastatin treatment on serum adiponectin concentrations in patients with dislipidemia.

PubMed

Moezzi, Atefeh; Parizadeh, Seyyed Mohammad Reza; Tavallaie, Shima; Mazidi, Mohsen; Afzali, Fariba; Adab, Afrouz; Ferns, Gordon; Ghayour Mobarhan, Majid

2014-08-01

Adiponectin is an adipose tissue-derived protein with anti-inflammatory properties. Statins are a class of cholesterol-lowering drugs, widely used for treatment of cardiovascular diseases. In the current study, we aimed to assess the effects of simvastatin on serum levels of adiponectin in patients with dyslipidemia, recruited from Ghaem Hospital, Mashhad, Iran. A total of 102 patients with dyslipidemia were treated with simvastatin or placebo during a double-blind, cross-over, placebo-controlled trial. The adiponectin levels were measured before and after each treatment period. Seventy seven participants completed the study. There was a significant reduction in serum total cholesterol (approxmately 21%), low density lipoprotein-cholesterol (LDL-C) (approxmately 28%), and triglycerides (approxmately 11%), after four weeks of treatment with simvastatin (P < 0.001). No significant change in serum adiponectin concentrations was observed after treatment with simvastatin. This may be because of the relatively short duration of treatment and longer treatment duration may be necessary to investigation in future studies.

Betaine Attenuates Alcohol-Induced Pancreatic Steatosis.

PubMed

Yang, Wenjuan; Gao, Jinhang; Tai, Yang; Chen, Meng; Huang, Luming; Wen, Shilei; Huang, Zhiyin; Liu, Rui; Li, Jing; Tang, Chengwei

2016-07-01

To explore the effect of betaine on alcoholic pancreatic steatosis and its mechanism. Rats were randomly assigned to control, ethanol, or ethanol + betaine groups. Changes in pancreatic morphology; serum lipid levels; and pancreatic lipid, amylase and lipase levels were determined. The serum and adipose tissue adiponectin level was measured by an enzyme-linked immunoassay. Adiponectin receptor-1 (AdipoR1), AdipoR2, sterol regulatory element binding protein-1c (SREBP-1c), SREBP-2, and fatty acid synthetase expression levels were quantified. The SREBP-1c expression in SW1990 cells treated with various concentrations of ethanol or ethanol plus betaine and/or adiponectin was assessed. Alcohol-induced changes in pancreatic morphology were attenuated by betaine. Pancreatic triglyceride, free fatty acid and expression levels of SREBP-1c and fatty acid synthetase were elevated after ethanol feeding but remained at control levels after betaine supplementation. Alcohol-induced decreases in serum and adipose tissue adiponectin, pancreatic AdipoR1, amylase, and lipase were attenuated by betaine. Serum triglyceride and free fatty acid levels were elevated after alcohol consumption and remained higher after betaine supplementation compared with controls. Betaine and/or adiponectin suppressed alcohol-induced SREBP-1c upregulation in vitro. Betaine attenuated alcoholic-induced pancreatic steatosis most likely by suppressing pancreatic SREBP-1c both directly and through the restoration of adiponectin signaling.

Molecular evolution of adiponectin in Carnivora and its mRNA expression in relation to hepatic lipidosis.

PubMed

Nieminen, Petteri; Rouvinen-Watt, Kirsti; Kapiainen, Suvi; Harris, Lora; Mustonen, Anne-Mari

2010-09-15

Adiponectin is a novel adipocyte-derived hormone with low circulating concentrations and/or mRNA expression in obesity and non-alcoholic fatty liver disease (NAFLD). The adiponectin mRNA of several Carnivora species was sequenced to enable further gene expression studies in this clade with potential experimental species to examine the connections of hypoadiponectinemia to hepatic lipidosis. In addition, adiponectin mRNA expression was studied in the retroperitoneal fat of the American mink (Neovison vison), as hepatic lipidosis with close similarities to NAFLD can be rapidly induced to the species by fasting. The mRNA expression was determined after overnight-7d of food deprivation and 28d of re-feeding and correlated to the liver fat %. The homologies between the determined carnivoran mRNA sequences and that of the domestic dog were 92.2-99.1%. As the mRNA expression was not affected by short-term fasting and did not correlate with the liver fat %, there seems to be no clear connection between adiponectin and the development of lipidosis in the American mink. In the future, the obtained sequences can be utilized in further studies of adiponectin expression in comparative endocrinology. Copyright (c) 2010 Elsevier Inc. All rights reserved.

ADIPOQ single nucleotide polymorphism: Association with adiponectin and lipoproteins levels restricted to men

PubMed Central

Tureck, Luciane Viater; Leite, Neiva; Souza, Ricardo Lehtonen Rodrigues; da Silva Timossi, Luciana; Osiecki, Ana Claudia Vecchi; Osiecki, Raul; Alle, Lupe Furtado

2015-01-01

Adiponectin is an adipokine inversely correlated with obesity, which has beneficial effect on insulin resistance and lipid metabolism. Considering its potential as a therapeutic target in the metabolic disorder contexts, and in order to add knowledge in the area, our study evaluated the ADIPOQ 276G > T polymorphism effect on adiponectin levels, and on lipoproteins of clinical interest in a population sample composed of 211 healthy individuals. Significant effects were observed only among men: the carriers of heterozygous genotype (GT) showed high levels of adiponectin (p = 0.018), while the rare homozygous genotype (TT) gave its carriers a negative phenotype, represented by higher levels of low density lipoprotein cholesterol (LDL-C) (p = 0.004 and p = 0.005) and total cholesterol (TC) (p = 0.010 and p = 0.005) compared to carriers of other genotypes (GG and GT respectively), the independent effect of SNP on LDL-C and TC levels was confirmed by multiple regression analysis (p = 0.008 and p = 0.044). We found no evidence of correlation between circulating adiponectin levels and biochemical markers, which suggests, therefore, an SNP 276G > T independent effect on adiponectin levels and on lipoprotein metabolism in men enrolled in this study. PMID:26137445

Impact of Weight Loss on Plasma Leptin and Adiponectin in Overweight-to-Obese Post Menopausal Breast Cancer Survivors.

PubMed

Thompson, Henry J; Sedlacek, Scot M; Wolfe, Pamela; Paul, Devchand; Lakoski, Susan G; Playdon, Mary C; McGinley, John N; Matthews, Shawna B

2015-06-26

Women who are obese at the time of breast cancer diagnosis have higher overall mortality than normal weight women and some evidence implicates adiponectin and leptin as contributing to prognostic disadvantage. While intentional weight loss is thought to improve prognosis, its impact on these adipokines is unclear. This study compared the pattern of change in plasma leptin and adiponectin in overweight-to-obese post-menopausal breast cancer survivors during weight loss. Given the controversies about what dietary pattern is most appropriate for breast cancer control and regulation of adipokine metabolism, the effect of a low fat versus a low carbohydrate pattern was evaluated using a non-randomized, controlled study design. Anthropometric data and fasted plasma were obtained monthly during the six-month weight loss intervention. While leptin was associated with fat mass, adiponectin was not, and the lack of correlation between leptin and adiponectin concentrations throughout weight loss implies independent mechanisms of regulation. The temporal pattern of change in leptin but not adiponectin was affected by magnitude of weight loss. Dietary pattern was without effect on either adipokine. Mechanisms not directly related to dietary pattern, weight loss, or fat mass appear to play dominant roles in the regulation of circulating levels of these adipokines.

Impact of Weight Loss on Plasma Leptin and Adiponectin in Overweight-to-Obese Post Menopausal Breast Cancer Survivors

PubMed Central

Thompson, Henry J.; Sedlacek, Scot M.; Wolfe, Pamela; Paul, Devchand; Lakoski, Susan G.; Playdon, Mary C.; McGinley, John N.; Matthews, Shawna B.

2015-01-01

Women who are obese at the time of breast cancer diagnosis have higher overall mortality than normal weight women and some evidence implicates adiponectin and leptin as contributing to prognostic disadvantage. While intentional weight loss is thought to improve prognosis, its impact on these adipokines is unclear. This study compared the pattern of change in plasma leptin and adiponectin in overweight-to-obese post-menopausal breast cancer survivors during weight loss. Given the controversies about what dietary pattern is most appropriate for breast cancer control and regulation of adipokine metabolism, the effect of a low fat versus a low carbohydrate pattern was evaluated using a non-randomized, controlled study design. Anthropometric data and fasted plasma were obtained monthly during the six-month weight loss intervention. While leptin was associated with fat mass, adiponectin was not, and the lack of correlation between leptin and adiponectin concentrations throughout weight loss implies independent mechanisms of regulation. The temporal pattern of change in leptin but not adiponectin was affected by magnitude of weight loss. Dietary pattern was without effect on either adipokine. Mechanisms not directly related to dietary pattern, weight loss, or fat mass appear to play dominant roles in the regulation of circulating levels of these adipokines. PMID:26132992

Inhibition of Angiotensin II-Induced Cardiac Fibrosis by Atorvastatin in Adiponectin Knockout Mice.

PubMed

Choi, Sun Young; Park, Jong Sung; Roh, Mee Sook; Kim, Chong-Rak; Kim, Moo Hyun; Serebruany, Victor

2017-05-01

Adiponectin is a polypeptide known to inhibit cardiac fibrosis via the activation of ‎adenosine monophosphate-activated protein kinase (AMPK). Statins can also activate AMPK, resulting in the secretion of adiponectin. We determined whether atorvastatin inhibits angiotensin II-induced cardiac fibrosis (AICF) in the presence or absence of adiponectin. Adiponectin knockout (APN-KO, n = 44) and wild type (WT, n = 44) mice were received subcutaneous angiotensin II (1.5 mg/kg/day), and atorvastatin (10 mg/kg/day) was administered orally for 15 days. The mRNA expression levels of collagen type I and III, as well as AMPK phosphorylation levels in cardiac tissue were then measured. In the APN-KO mice, collagen type I (p < 0.001) and type III (p = 0.001) expression was significantly greater when treated with angiotensin II, while their expression was significantly reduced in the presence of angiotensin II and atorvastatin. Relative AMPK phosphorylation levels in APN-KO mice were also significantly higher in the angiotensin II + atorvastatin group when compared with angiotensin II group alone. We conclude that atorvastatin attenuates AICF independently from adiponectin by activating AMPK. These data suggest potential cardioprotection beyond lipid modulation potentially supporting statin pleiotropic hypothesis.

Effect of adiponectin and sex steroid hormones on bone mineral density and bone formation markers in postmenopausal women with subclinical hyperthyroidism.

PubMed

Ahn, Ki Hoon; Lee, Seung Hyeun; Park, Hyun Tae; Kim, Tak; Hur, Jun Young; Kim, Young Tae; Kim, Sun Haeng

2010-04-01

The relationship between adiponectin and sex hormones with bone mineral density (BMD) and bone formation markers was investigated in postmenopausal women with subclinical hyperthyroidism (SCH). Seventy-five postmenopausal women were selected among the patients who participated in a health screening program in 2007. Thirty-seven control women with normal thyroid function were matched to 38 women with SCH by age, body mass index (BMI), and years since menopause (YSM). The associations between adiponectin and sex hormones with lumbar spine BMD and bone turnover markers were investigated. Adiponectin, testosterone (T; total and free forms), and thyroid-stimulating hormone were significantly different between the women with SCH and euthyroid. After adjusting for age, BMI, and YSM, free T (r = 0.351; P = 0.029) and estradiol (E2; r = -0.368; P = 0.024) had significant associations with bone alkaline phosphatase (B-ALP). Total T (r = 0.388; P = 0.021) and E2 (r = -0.376; P = 0.026) had significant associations with osteocalcin. However, there were no significant associations between adiponectin and sex hormones with the BMD levels in the SCH subjects. There were correlations between sex hormones with B-ALP and osteocalcin, but no associations between adiponectin and sex hormones with the lumbar spine BMD in postmenopausal SCH patients.

Effects of eicosapentaenoic acid on endothelial cell-derived microparticles, angiopoietins and adiponectin in patients with type 2 diabetes.

PubMed

Nomura, Shosaku; Shouzu, Akira; Omoto, Seitarou; Inami, Norihito; Ueba, Tetsuya; Urase, Fumiaki; Maeda, Yasuhiro

2009-04-01

The aim of this study was to evaluate the significance of endothelial cell-derived microparticles (EDMP), angiopoietin-2 (Ang-2) and adiponectin in hyperlipidemic patients with and without type 2 diabetes mellitus, and to compare the two for the effects of eicosapentaenoic acid (EPA) on these markers. One hundred and twenty-six hyperlipidemic patients with and without type 2 diabetes mellitus received EPA 1,800 mg daily, and 50 of the patients were non-diabetic. EDMP and Ang-2 levels prior to treatment were higher in diabetic patients than in non-diabetic patients, whereas adiponectin levels were lower in diabetics. When diabetic patients were classified into two groups on the basis of Ang-2 levels, the levels of all markers remained unchanged in those without a high Ang-2 level after EPA treatment. In contrast, all markers except for adiponectin were decreased significantly in diabetic patients with high Ang-2 levels after 6 months of EPA treatment. These diabetic patients with high Ang-2 levels displayed a more significant increase in adiponectin levels after EPA treatment than those who did not. These results suggest that EPA possesses an adiponectin-dependent anti-atherosclerotic effect and may be beneficial for the prevention of vascular complications in diabetic patients with high Ang-2 levels.

Leptin and adiponectin in patients with systemic lupus erythematosus: clinical and laboratory correlations.

PubMed

Barbosa, Vitalina de Souza; Francescantônio, Paulo Luiz; Silva, Nílzio Antônio da

2015-01-01

To evaluate the serum levels of leptin and adiponectin in patients with systemic lupus erythematosus (SLE) and correlate their levels with disease activity, presence of autoantibodies and clinical manifestations. 52 women with SLE and 33 healthy women were evaluated. The patients were divided into two groups, the first with active SLE and the second with inactive SLE. Patients with SLEDAI ≥3 were considered active. Serum levels of leptin (ng/ml) and adiponectin (μg/ml) were measured by enzyme immunoassay. There was a significant difference in leptin levels between SLE and controls (20.7 ± 17.1 vs. 8.0 ± 5.0 ng/mL, P <0.001), but no significant difference in adiponectin levels (87.5 ± 69.7 vs. 118.1 ± 70.6 pg/ml, P = 0.053). No significant difference in levels of leptin and adiponectin was noted between inactive and active SLE groups. There was a significant association between low levels of leptin and positivity for anticardiolipin (aCL) (P = 0.025) and lupus anticoagulant (LA) (p = 0.003) and a significant association between high levels of leptin and the presence of renal disease (p <0.001). However, there was no association between adiponectin levels with autoantibodies and clinical features in SLE patients. Patients with SLE had elevated leptin levels, with association with renal involvement. Leptin and adiponectin were not correlated with disease activity. Low levels of leptin have been associated with the presence of LA and aCL. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Effect of Green Tea on Plasma Adiponectin Levels: A Systematic Review and Meta-analysis of Randomized Controlled Clinical Trials.

PubMed

Haghighatdoost, Fahimeh; Nobakht M Gh, B Fatemeh; Hariri, Mitra

2017-01-01

Our objective was to perform a systematic review and meta-analysis on randomized controlled trials (RCTs) assessing the effect of green tea on serum adiponectin concentration. We searched PubMed, ISI Web of Science, Scopus, and the Google Scholar databases up to November 2016. RCTs conducted among human adults studied the effects of green tea and green tea extract on serum adiponectin concentrations as an outcome variable was included. The weighted mean differences and standard deviations (SD) of change in serum adiponectin levels were calculated. The random effects model was used for deriving a summary of mean estimates with their corresponding SDs. The protocol was registered with PROSPERO (No. CRD42017057716). Fourteen RCTs were eligible to be included in the systematic review and the meta-analysis. Our analysis showed that green tea did not significantly affect adiponectin concentrations in comparison with placebo (weighted mean difference = -0.02 µg/ml, 95% confidence interval [CI], -0.41, 0.38; p = 0.936). There was a substantial heterogeneity between studies (I 2 = 91.7%; p < 0.0001). Subgroup analyses based on sex, type of intervention, continent, and body mass index (BMI) could not explain the sources of heterogeneity. Metaregression analyses revealed that the dose and duration of green tea ingestion did not have any effect on adiponectin concentrations. Green tea could not change the circulatory adiponectin levels. The dose and duration of green tea could not change the result. RCTs with longer follow-up periods and higher doses are needed to replicate our results.

Adiponectin, insulin resistance, and left ventricular structure in dipper and nondipper essential hypertensive patients.

PubMed

Della Mea, Paolo; Lupia, Mario; Bandolin, Valentina; Guzzon, Samuele; Sonino, Nicoletta; Vettor, Roberto; Fallo, Francesco

2005-01-01

Adiponectin is an adipocyte-derived protein with insulin-sensitizing and antiatherogenic properties. Failure to decrease blood pressure (BP) normally during night in hypertensive patients has been independently associated with left ventricular hypertrophy. We examined the relationship between adiponectin levels, insulin sensitivity, and left ventricular structure in 40 newly diagnosed never-treated patients with essential hypertension, including 20 patients with a normal night-time pressure decrease (ie, dippers) and 20 patients with BP persistently elevated throughout the 24-h period (ie, nondippers). All subjects had grade 1-2 hypertension, aged 18 to 65 years, no diabetes mellitus, no obesity, no hyperlipidemia, and no cardiopulmonary, renal, or hepatic disease. The two groups of patients were similar for age, sex, body mass index, and had no differences for clinic, 24-h, and diurnal BP, and 24-h, diurnal, and nocturnal heart rate, as well as glucose, total cholesterol, and triglyceride levels. Plasma insulin and homeostasis model assessment (HOMA index) were higher (P < .01), and adiponectin levels were lower (P < .005) in nondippers than in dippers. Adiponectin correlated inversely with HOMA index and insulin levels (r = -0.58, and r = -0.62, respectively, P < .001) in the entire population. Nondippers showed left ventricular mass, relative wall thickness, and measure of early and late diastolic peak flow velocity ratio similar to those of dippers. In the absence of major cardiovascular risk factors, nondipper essential hypertensive patients show more prominent insulin resistance and lower adiponectin compared to dippers. Therapeutic modulation of adiponectin or insulin resistance might provide additional benefit to the conventional antihypertensive treatment.

Second trimester amniotic fluid adiponectin level is affected by maternal tobacco exposure, insulin, and PAPP-A level.

PubMed

De Leon-Luis, Juan; Perez, Ricardo; Pintado Recarte, Pilar; Avellaneda Fernandez, Alfredo; Romero Roman, Carlos; Antolin Alvarado, Eugenia; Ortiz-Quintana, Luis; Izquierdo Martinez, Maravillas

2012-12-01

Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and antiatherosclerotic properties. The objectives of the present study were to determine the amniotic fluid (AF) concentration of adiponectin during the second trimester of pregnancy and to demonstrate its association with maternal and fetal variables and AF concentrations of insulin, leptin, and pregnancy-associated-plasma-protein A (PAPP-A). We performed a cross-sectional study of 222 pregnant women who underwent amniocentesis at 15-18 weeks for genetic reasons. No malformation or chromosomal disorder was found in the newborn after birth. AF adiponectin, leptin, PAPP-A, and insulin concentrations were measured using commercially available assays. All maternal, fetal, and biochemical variables were studied using univariate and multivariate linear regression analysis to determine their association with the AF concentration of adiponectin. Adiponectin concentration was negatively correlated with maternal smoking status (β=-5.208; p<0.001) and positively correlated with levels of insulin (β=0.621; p=0.002) and PAPP-A (β=40.150; p<0.001). Non-significant correlations were found between adiponectin concentration and maternal age, maternal body mass index, gestational age at amniocentesis, fetal gender, and AF level of leptin. These findings suggest that the fetus and its membrane adipocytokines, in relationship with maternal and other fetal variables, play a dynamic role in the regulation of energy and oxidative stress homeostasis due to its insulin-sensitizing and antiatherosclerotic effects. The association of these molecules with maternal tobacco consumption during pregnancy could have perinatal implications. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Melatonin modulates adiponectin expression on murine colitis with sleep deprivation.

PubMed

Kim, Tae Kyun; Park, Young Sook; Baik, Haing-Woon; Jun, Jin Hyun; Kim, Eun Kyung; Sull, Jae Woong; Sung, Ho Joong; Choi, Jin Woo; Chung, Sook Hee; Gye, Myung Chan; Lim, Ju Yeon; Kim, Jun Bong; Kim, Seong Hwan

2016-09-07

To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation. The following five groups of C57BL/6 mice were used in this study: (1) group I, control; (2) group II, 2% DSS induced colitis for 7 d; (3) group III, 2% DSS induced colitis and melatonin treatment; (4) group IV, 2% DSS induced colitis with sleep deprivation (SD) using specially designed and modified multiple platform water baths; and (5) group V, 2% DSS induced colitis with SD and melatonin treatment. Melatonin (10 mg/kg) or saline was intraperitoneally injected daily to mice for 4 d. The body weight was monitored daily. The degree of colitis was evaluated histologically after sacrificing the mice. Immunohistochemical staining and Western blot analysis was performed using anti-adiponectin antibody. After sampling by intracardiac punctures, levels of serum cytokines were measured by ELISA. Sleep deprivation in water bath exacerbated DSS induced colitis and worsened weight loss. Melatonin injection not only alleviated the severity of mucosal injury, but also helped survival during stressful condition. The expression level of adiponectin in mucosa was decreased in colitis, with the lowest level observed in colitis combined with sleep deprivation. Melatonin injection significantly (P < 0.05) recovered the expression of adiponectin. The expression levels of IL-6 and IL-17 were increased in the serum of mice with DSS colitis but decreased after melatonin injection. This study suggested that melatonin modulated adiponectin expression in colonic tissue and melatonin and adiponectin synergistically potentiated anti-inflammatory effects on colitis with sleep deprivation.

Effects of individual and combined dietary weight loss and exercise interventions in postmenopausal women on adiponectin and leptin levels

PubMed Central

Abbenhardt, Clare; McTiernan, Anne; Alfano, Catherine M.; Wener, Mark H.; Campbell, Kristin L.; Duggan, Catherine; Foster-Schubert, Karen E.; Kong, Angela; Toriola, Adetunji T; Potter, John D.; Mason, Caitlin; Xiao, Liren; Blackburn, George L.; Bain, Carolyn; Ulrich, Cornelia M.

2013-01-01

Background Excess body weight and a sedentary lifestyle are associated with the development of several diseases, including cardiovascular disease, diabetes, and cancer in women. One proposed mechanism linking obesity to chronic diseases is an alteration in adipose-derived adiponectin and leptin levels. We investigated the effects of 12-month reduced calorie, weight loss and exercise interventions on adiponectin and leptin concentrations. Methods Overweight/obese postmenopausal women (n=439) were randomized as follows: 1) a reduced calorie, weight loss diet (diet; N=118); 2) moderate-to-vigorous intensity aerobic exercise (exercise; N=117); 3) a combination of a reduced calorie, weight loss diet and moderate-to-vigorous intensity aerobic exercise (diet+exercise; N=117); or 4) control (N=87). The reduced calorie diet had a 10% weight loss goal. The exercise intervention consisted of 45 minutes of moderate-to-vigorous aerobic activity 5 days/week. Adiponectin and leptin levels were measured at baseline and after 12 months of intervention using a radioimmunoassay. Results Adiponectin increased by 9.5 % in the diet group and 6.6 % in the diet+exercise group (both p≤0.0001 vs. control). Compared with controls, leptin decreased with all interventions (diet+exercise, −40.1%, p<0.0001; diet, −27.1%, p<0.0001; exercise, −12.7%, p=0.005). The results were not influenced by the baseline body mass index (BMI). The degree of weight loss was inversely associated with concentrations of adiponectin (diet, p-trend=0.0002; diet+exercise, p-trend=0.0005) and directly associated with leptin (diet, p-trend<0.0001; diet+exercise, p-trend<0.0001). Conclusion Weight loss through diet or diet+exercise increased adiponectin concentrations. Leptin concentrations decreased in all of the intervention groups, but the greatest reduction occurred with diet+exercise. Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin. PMID:23432360

Effect of Persea americana (avocado) fruit extract on the level of expression of adiponectin and PPAR-γ in rats subjected to experimental hyperlipidemia and obesity.

PubMed

Padmanabhan, Monika; Arumugam, Geetha

2014-06-01

Persea americana, commonly known as avocado, is traditionally consumed fruit which possesses body fat lowering capacity. Adiponectin plays an important role in regulating obesity. In this study, the effect of hydro-alcoholic fruit extract of P. americana (HAEPA) on the level of blood lipids, glutathione, lipid peroxidation products, adiponectin and peroxisome proliferator activated receptor (PPAR)-γ expressions was investigated in rats fed a high-fat diet (HFD). Male Sprague Dawley rats were divided into four groups: groups 1 and 2 were fed normal rat chow (5% fat) and groups 3 and 4 were fed HFD (23% fat) for a period of 14 weeks. In addition, groups 2 and 4 rats were administered orally with 100 mg/kg body weight of HAEPA from third week. After 14 weeks, rats were sacrificed, and serum/plasma levels of total cholesterol, phospholipids, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and adiponectin were determined. The mRNA expression of adiponectin, PPAR-γ and protein expression of PPAR-γ were also evaluated. The body mass index (BMI), total fat pad mass and adiposity index were significantly decreased in HAEPA co-administered rats than in HFD-fed rats. The levels of LDL and lipid peroxides were significantly higher in HFD group than in HFD+HAEPA group. Levels of reduced glutathione, adiponectin, mRNA expression of adiponectin, PPAR-γ and protein expression of PPAR-γ were found to be increased in HFD+HAEPA group than in HFD group. The hypolipidemic effect of HAEPA is also evidenced by the histological observations in liver, heart and adipose tissue. The results indicate that HAEPA exhibits hypolipidemic activity probably by increasing the mRNA expression of adiponectin and PPAR-γ, which reduce the risk of hyperlipidemia and obesity.

Serum Concentrations of Leptin and Adiponectin in Dogs with Myxomatous Mitral Valve Disease.

PubMed

Kim, H-S; Kang, J-H; Jeung, E-B; Yang, M-P

2016-09-01

The concentrations of circulating adipokines in dogs with myxomatous mitral valve disease (MMVD) have not been investigated in detail. To determine whether serum concentrations of adipokines differ between healthy dogs and dogs with MMVD and whether circulating concentrations depend on the severity of heart failure resulting from MMVD. In the preliminary study, 30 healthy dogs and 17 client-owned dogs with MMVD, and in the subsequent study, 30 healthy dogs and 46 client-owned dogs with MMVD. Prospective case-controlled observational study. In the preliminary study, serum concentrations of leptin, adiponectin, resistin, visfatin, interleukin (IL)-1β, IL-6, IL-10, IL-18, and tumor necrosis factor-α were measured. In the subsequent study, MMVD dogs were divided into three groups according to the International Small Animal Cardiac Health Council (ISACHC) classification, and serum concentrations of leptin and adiponectin were measured. In the preliminary study, serum leptin and adiponectin concentrations differed significantly between dogs with MMVD and healthy dogs. Serum leptin (P = .0013) concentrations were significantly higher in dogs with MMVD than in healthy dogs, whereas adiponectin (P = .0009) concentrations were significantly lower in dogs with MMVD. However, we observed no significant differences in the other variables. In the subsequent study, dogs classified as ISACHC class 3 had higher serum concentrations of leptin (P = .0022) than healthy dogs but ISACHC class 1 or 2 dogs did not. Serum adiponectin concentrations were significantly lower in ISACHC class 1 (P < .0001) dogs than in healthy dogs, whereas adiponectin concentrations in ISACHC class 3 dogs were significantly higher than in ISACHC class 1 dogs (P = .0081). Circulating concentrations of leptin and adiponectin might be altered in dogs with MMVD. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Effects of adrenal hormones on the expression of adiponectin and adiponectin receptors in adipose tissue, muscle and liver.

PubMed

de Oliveira, Cristiane; Iwanaga-Carvalho, Carla; Mota, João F; Oyama, Lila M; Ribeiro, Eliane B; Oller do Nascimento, Cláudia M

2011-11-01

Adiponectin, an insulin-sensitive hormone that is primarily synthesized in adipose tissue, exerts its effects by binding to two receptors, adipoR1 and adipoR2. Little is known regarding the effects of glucocorticoids on the expression of adiponectin receptors. Male Wistar rats were bilaterally adrenalectomized and treated with dexamethasone (0.2 mg/100 g) twice daily for 3 days. To analyze the potential effects of glucocorticoids, rats received two daily injections of the glucocorticoid receptor antagonist (RU-486, 5.0 mg) over the course of 3 days. Additionally, 3T3-L1 adipocytes and C2C12 myotubes were treated with dexamethasone, adrenaline or RU-486. The gene expression of adiponectin, adipoR1 and adipoR2 was determined by real-time PCR, and protein secretion was examined by Western blotting using lysates from retroperitoneal, epididymal and subcutaneous adipose tissue depots, liver and muscle. In rats, excess glucocorticoids increased the levels of insulin in serum and decreased serum adiponectin concentrations, whereas adrenalectomy decreased the mRNA expression of adiponectin (3-fold) and adipoR2 (7-fold) in epididymal adipose tissue and increased adipoR2 gene expression in muscle (3-fold) compared to control group sham-operated. Dexamethasone treatment did not reverse the effects of adrenalectomy, and glucocorticoid receptor blockade did not reproduce the effects of adrenalectomy. In 3T3-L1 adipocytes, dexamethasone and adrenaline both increased adipoR2 mRNA levels, but RU-486 reduced adipoR2 gene expression in vitro. Dexamethasone treatment induces a state of insulin resistance but does not affect adiponectin receptor expression in adipose tissue. However, the effects of catecholamines on insulin resistance may be due to their effects on adipoR2. Copyright © 2011 Elsevier Inc. All rights reserved.

Adiponectin Provides Additional Information to Conventional Cardiovascular Risk Factors for Assessing the Risk of Atherosclerosis in Both Genders

PubMed Central

Yoon, Jin-Ha; Kim, Sung-Kyung; Choi, Ho-June; Choi, Soo-In; Cha, So-Youn; Koh, Sang-Baek

2013-01-01

Background This study evaluated the relation between adiponectin and atherosclerosis in both genders, and investigated whether adiponectin provides useful additional information for assessing the risk of atherosclerosis. Methods We measured serum adiponectin levels and other cardiovascular risk factors in 1033 subjects (454 men, 579 women) from the Korean Genomic Rural Cohort study. Carotid intima–media-thickness (CIMT) was used as measure of atherosclerosis. Odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated using multiple logistic regression, and receiver operating characteristic curves (ROC), the category-free net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. Results After adjustment for conventional cardiovascular risk factors, such as age, waist circumference, smoking history, low-density and high-density lipoprotein cholesterol, triglycerides, systolic blood pressure and insulin resistance, the ORs (95%CI) of the third tertile adiponectin group were 0.42 (0.25–0.72) in men and 0.47 (0.29–0.75) in women. The area under the curve (AUC) on the ROC analysis increased significantly by 0.025 in men and 0.022 in women when adiponectin was added to the logistic model of conventional cardiovascular risk factors (AUC in men: 0.655 to 0.680, p = 0.038; AUC in women: 0.654 to 0.676, p = 0.041). The NRI was 0.32 (95%CI: 0.13–0.50, p<0.001), and the IDI was 0.03 (95%CI: 0.01–0.04, p<0.001) for men. For women, the category-free NRI was 0.18 (95%CI: 0.02–0.34, p = 0.031) and the IDI was 0.003 (95%CI: −0.002–0.008, p = 0.189). Conclusion Adiponectin and atherosclerosis were significantly related in both genders, and these relationships were independent of conventional cardiovascular risk factors. Furthermore, adiponectin provided additional information to conventional cardiovascular risk factors regarding the risk of atherosclerosis. PMID:24116054

Adiponectin provides additional information to conventional cardiovascular risk factors for assessing the risk of atherosclerosis in both genders.

PubMed

Yoon, Jin-Ha; Kim, Sung-Kyung; Choi, Ho-June; Choi, Soo-In; Cha, So-Youn; Koh, Sang-Baek; Kang, Hee-Taik; Ahn, Song Vogue

2013-01-01

This study evaluated the relation between adiponectin and atherosclerosis in both genders, and investigated whether adiponectin provides useful additional information for assessing the risk of atherosclerosis. We measured serum adiponectin levels and other cardiovascular risk factors in 1033 subjects (454 men, 579 women) from the Korean Genomic Rural Cohort study. Carotid intima-media-thickness (CIMT) was used as measure of atherosclerosis. Odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated using multiple logistic regression, and receiver operating characteristic curves (ROC), the category-free net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. After adjustment for conventional cardiovascular risk factors, such as age, waist circumference, smoking history, low-density and high-density lipoprotein cholesterol, triglycerides, systolic blood pressure and insulin resistance, the ORs (95%CI) of the third tertile adiponectin group were 0.42 (0.25-0.72) in men and 0.47 (0.29-0.75) in women. The area under the curve (AUC) on the ROC analysis increased significantly by 0.025 in men and 0.022 in women when adiponectin was added to the logistic model of conventional cardiovascular risk factors (AUC in men: 0.655 to 0.680, p = 0.038; AUC in women: 0.654 to 0.676, p = 0.041). The NRI was 0.32 (95%CI: 0.13-0.50, p<0.001), and the IDI was 0.03 (95%CI: 0.01-0.04, p<0.001) for men. For women, the category-free NRI was 0.18 (95%CI: 0.02-0.34, p = 0.031) and the IDI was 0.003 (95%CI: -0.002-0.008, p = 0.189). Adiponectin and atherosclerosis were significantly related in both genders, and these relationships were independent of conventional cardiovascular risk factors. Furthermore, adiponectin provided additional information to conventional cardiovascular risk factors regarding the risk of atherosclerosis.

Comparison of plasma adiponectin & certain inflammatory markers in angiographically proven coronary artery disease patients with & without diabetes – A study from India

PubMed Central

Kumpatla, Satyavani; Karuppiah, Kirubakaran; Immaneni, Sathyamurthy; Muthukumaran, Parthiban; Krishnan, Jayanthi; Narayanamoorthy, Srinivasan Kanthallu; Viswanathan, Vijay

2014-01-01

Background & objectives: The association between adiponectin and risk of cardiovascular disease is well known. The aim of the present study was to evaluate adiponectin and certain inflammatory markers and to determine the correlations between them in angiographically proven coronary artery disease (CAD) in subjects with and without diabetes. Methods: A total of 180 subjects who underwent coronary angiography for symptoms suggestive of CAD were categorised into groups based on their diabetes and/or CAD status: group1 (non-diabetic non-CAD); group2 (non-diabetic CAD); group3 (diabetic non-CAD) and group4 (diabetic CAD). Adiponectin, tumour necrosis factor α (TNF-α) and soluble form of E-selectin (sE-selectin) were estimated using quantitative sandwich enzyme immunoassay and high sensitive C-reactive protein (hsCRP) by particle enhanced immunoturbidimetric method. Results: Adiponectin levels were significantly lower in subjects with either diabetes or CAD and were much lower in subjects who had both. hsCRP was elevated in CAD and diabetes but did not differ significantly between groups. sE-selectin and TNF-α levels were elevated in CAD. Adiponectin negatively correlated with age, glucose, sE-selectin, total and LDL cholesterol. hsCRP correlated with BMI, sE-selectin and urea. sE-selectin correlated with BMI, triglycerides and VLDL cholesterol, whereas TNF-α correlated with fasting plasma glucose. In the logistic regression analysis, adiponectin had a significant inverse association with CAD. sE-selectin and TNF-α also showed significant independent association with CAD. Interpretation & conclusions: Adiponectin and other inflammatory markers such as sE-selectin and TNF-α showed a significant association with CAD. Hence, early assessment of such markers can help to identify high risk patients, and to reduce the inflammatory component of diabetes and CAD. PMID:25109718

Adiponectin and vitamin D-binding protein are independently associated at birth in both mothers and neonates.

PubMed

Karras, Spyridon N; Polyzos, Stergios A; Newton, Danforth A; Wagner, Carol L; Hollis, Bruce W; Ouweland, Jody van den; Dursun, Erdinc; Gezen-Ak, Duygu; Kotsa, Kalliopi; Annweiler, Cedric; Naughton, Declan P

2018-01-01

Adult body fat is associated with birth anthropometry, suggesting a role for metabolic regulators including vitamin D and the adipokines-adiponectin and irisin-which have been reported to interact but, as yet, data remain controversial. To study (i) the relationship between vitamin D, its binding protein (VDBP) and the adipokines, adiponectin, and irisin in mothers and neonates at birth and (ii) their effects on neonate anthropometric outcomes. Cross-sectional study for healthy mothers with full-term and uncomplicated births. Primary care. Seventy pairs of newly delivered neonates and their mothers. Biochemical markers from maternal and cord: VDBP, adiponectin, irisin, calcium, albumin, parathyroid hormone, 25OHD, 1,25(OH) 2 D. Maternal demographic and social characteristics and neonate anthropometric parameters were recorded. Maternal VDBP levels (364.1 ± 11.9 μg/ml) demonstrated a strong positive correlation with maternal adiponectin (4.4 ± 0.4 μg/ml) and irisin (308.8 ± 50.8 ng/ml) concentrations, which remained significant (p < 0.001 and p < 0.041, respectively) after adjustment with multiple parameters, including weeks of gestation, maternal age, and BMI. The finding of a strong association of VDBP (355.3 ± 29.2 μg/ml) and adiponectin (11.9 ± 2.0 μg/ml) but not irisin (174.4 ± 26.0 ng/ml) was also evident in neonates (p = 0.03 and p = 0.94, respectively). No association was observed in both maternal and neonatal vitamin D, adiponectin, and irisin. The main findings of this study are (i) the perspective of a potential independent interaction of VDBP and adiponectin in both mothers and neonates and (ii) the lack of a causative model effect of both maternal/neonatal vitamin D status and adipokine profile on neonatal anthropometry at birth, as a surrogate marker of future metabolic health of the offspring.

Psoriasis is associated with decreased plasma adiponectin levels independently of cardiometabolic risk factors

PubMed Central

Li, R. C.; Krishnamoorthy, P.; DerOhannessian, S.; Doveikis, J.; Wilcox, M.; Thomas, P.; Rader, D. J.; Reilly, M. P.; Voorhees, A. Van; Gelfand, J. M.; Mehta, N. N.

2013-01-01

Summary Background Psoriasis is an inflammatory skin disease that may be associated with an adverse cardiometabolic profile including modulated plasma adiponectin and leptin levels. Whether these levels are independent of cardiometabolic risk factors, which are also prevalent in psoriasis, is not known. Methods A consecutive sample of 122 participants with varying degrees of psoriasis severity, and a random sample of 134 participants without psoriasis were recruited for this case–control study. Cardiometabolic risk factors including traditional cardiovascular risk factors, waist circumference, insulin resistance, and total plasma adiponectin and leptin were measured. Total plasma adiponectin and leptin levels were compared in unadjusted and adjusted analyses by psoriasis status. Results Participants with psoriasis had mostly mild disease and were mainly on topical therapies, but still had a more adverse cardiometabolic profile compared with those without psoriasis. Furthermore, plasma adiponectin levels were significantly lower in participants with psoriasis than those without {7.13 µg/mL [interquartile range (IQR) 4.9–11.3) vs. 14.5 µg/mL (IQR 8.4–24.1); P < 0.001]}. Plasma leptin (ng/mL) levels were higher in the psoriasis group but this did not reach statistical significance [11.3 (IQR 6.4–21.8) vs. 9.8 (IQR 4.9–20.5); P = 0.07]. In multivariable modelling, plasma adiponectin levels were still negatively associated with psoriasis status after adjusting for waist size (% difference = −41.2%, P < 0.001), insulin resistance (% difference = −39.5%, P < 0.001) and both waist size and insulin resistance (% difference = −38.5%, P < 0.001) Conclusion Plasma levels of adiponectin were lower in psoriasis, and this relationship persisted after adjusting for cardiometabolic risk factors known to decrease adiponectin levels. These findings suggest that inflammation present in psoriasis may be associated with adipose tissue dysfunction; however, direct studies of adipose tissue are needed to confirm this. PMID:24341476

Branched Chain Amino Acids Are Associated with Insulin Resistance Independent of Leptin and Adiponectin in Subjects with Varying Degrees of Glucose Tolerance.

PubMed

Connelly, Margery A; Wolak-Dinsmore, Justyna; Dullaart, Robin P F

2017-05-01

Branched chain amino acids (BCAA) may be involved in the pathogenesis of insulin resistance and are associated with type 2 diabetes mellitus (T2DM) development. Adipokines such as leptin and adiponectin influence insulin resistance and reflect adipocyte dysfunction. We examined the extent to which the association of BCAA with insulin resistance is attributable to altered leptin and adiponectin levels in individuals with varying degrees of glucose tolerance. BCAA were measured by nuclear magnetic resonance, whereas leptin and adiponectin were measured by immunoassay, in subjects with normal fasting glucose (n = 30), impaired fasting glucose (n = 25), and T2DM (n = 15). Insulin resistance was estimated by homeostasis model assessment (HOMAir). BCAA were higher in men than in women (P < 0.001) and tended to be higher in T2DM subjects (P = 0.10) compared to subjects with normal or impaired fasting glucose. In univariate regression analysis, BCAA were correlated with HOMAir (r = 0.46; P < 0.001) and inversely with adiponectin (r = -0.53; P < 0.001) but not with leptin (r = -0.08; P > 0.05). Multivariable linear regression analysis, adjusting for age, sex, T2DM, and body mass index (BMI), demonstrated that BCAA were positively associated with HOMAir (β = 0.242, P = 0.023). When BCAA, leptin, and adiponectin were included together, the positive relationship of HOMAir with BCAA (β = 0.275, P = 0.012) remained significant. Insulin resistance was associated with BCAA. This association remained after adjusting for age, sex, T2DM, BMI, as well as leptin and adiponectin. It is unlikely that the relationship of insulin resistance with BCAA is to a major extent attributable to effects of leptin and adiponectin.

Lower Adiponectin Levels at First Trimester of Pregnancy Are Associated With Increased Insulin Resistance and Higher Risk of Developing Gestational Diabetes Mellitus

PubMed Central

Lacroix, Marilyn; Battista, Marie-Claude; Doyon, Myriam; Ménard, Julie; Ardilouze, Jean-Luc; Perron, Patrice; Hivert, Marie-France

2013-01-01

OBJECTIVE To evaluate the associations between adiponectin levels and 1) the risk of developing gestational diabetes mellitus (GDM), and 2) insulin resistance/sensitivity, β-cell function, and compensation indices in a prospective cohort representative of the general population of pregnant women. RESEARCH DESIGN AND METHODS We performed anthropometric measurements and collected blood samples at 1st (6–13 weeks) and 2nd (24–28 weeks) trimesters. Diagnosis of GDM was made at 2nd trimester based on a 75-g oral glucose tolerance test (International Association of the Diabetes and Pregnancy Study Groups criteria). Insulin was measured (ELISA; Luminex) to estimate homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUCinsulin/glucose), and β-cell compensation (insulin secretion sensitivity index-2). Adiponectin was measured by radioimmunoassay. RESULTS Among the 445 participants included in this study, 38 women developed GDM. Women who developed GDM had lower 1st-trimester adiponectin levels (9.67 ± 3.84 vs. 11.92 ± 4.59 µg/mL in women with normal glucose tolerance). Lower adiponectin levels were associated with higher risk of developing GDM (OR, 1.12 per 1 µg/mL decrease of adiponectin levels; P = 0.02, adjusted for BMI and HbA1c at 1st trimester). Adiponectin levels at 1st and 2nd trimesters were associated with HOMA-IR (both: r = −0.22, P < 0.0001) and Matsuda index (r = 0.28, P < 0.0001, and r = 0.29, P < 0.0001). After adjustment for confounding factors, we found no significant association with HOMA-B and AUCinsulin/glucose. CONCLUSIONS Pregnant women with lower adiponectin levels at 1st trimester have higher levels of insulin resistance and are more likely to develop GDM independently of adiposity or glycemic measurements. PMID:23300287

Lower adiponectin levels at first trimester of pregnancy are associated with increased insulin resistance and higher risk of developing gestational diabetes mellitus.

PubMed

Lacroix, Marilyn; Battista, Marie-Claude; Doyon, Myriam; Ménard, Julie; Ardilouze, Jean-Luc; Perron, Patrice; Hivert, Marie-France

2013-06-01

To evaluate the associations between adiponectin levels and 1) the risk of developing gestational diabetes mellitus (GDM), and 2) insulin resistance/sensitivity, β-cell function, and compensation indices in a prospective cohort representative of the general population of pregnant women. We performed anthropometric measurements and collected blood samples at 1st (6-13 weeks) and 2nd (24-28 weeks) trimesters. Diagnosis of GDM was made at 2nd trimester based on a 75-g oral glucose tolerance test (International Association of the Diabetes and Pregnancy Study Groups criteria). Insulin was measured (ELISA; Luminex) to estimate homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUC(insulin/glucose)), and β-cell compensation (insulin secretion sensitivity index-2). Adiponectin was measured by radioimmunoassay. Among the 445 participants included in this study, 38 women developed GDM. Women who developed GDM had lower 1st-trimester adiponectin levels (9.67 ± 3.84 vs. 11.92 ± 4.59 µg/mL in women with normal glucose tolerance). Lower adiponectin levels were associated with higher risk of developing GDM (OR, 1.12 per 1 µg/mL decrease of adiponectin levels; P = 0.02, adjusted for BMI and HbA1c at 1st trimester). Adiponectin levels at 1st and 2nd trimesters were associated with HOMA-IR (both: r = -0.22, P < 0.0001) and Matsuda index (r = 0.28, P < 0.0001, and r = 0.29, P < 0.0001). After adjustment for confounding factors, we found no significant association with HOMA-B and AUC(insulin/glucose). Pregnant women with lower adiponectin levels at 1st trimester have higher levels of insulin resistance and are more likely to develop GDM independently of adiposity or glycemic measurements.

The association of SNP276G>T at adiponectin gene with insulin resistance and circulating adiponectin in response to two different hypocaloric diets.

PubMed

de Luis, Daniel Antonio; Izaola, Olatz; Primo, David; Aller, R; Ortola, A; Gómez, E; Lopez, J J

2018-03-01

Several adiponectin gene (ADIPOQ) single nucleotide polymorphisms (SNPS) have been related with adiponectin levels and risk for obesity. The aim of our study was to analyze the effect of rs1501299 ADIPOQ gene polymorphism and dietary intake on total adiponectin levels and insulin resistance after two hypocaloric diets in obese subjects. A Caucasian population of 284 obese patients was enrolled in a randomized clinical trial with two hypocaloric diets (I: moderate carbohydrates vs II: low fat). Before and after 12 weeks on each hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were realized. The statistical analysis was performed for the combined GT and TT as a group (mutant) and GG as second group (wild) (dominant model). The genotype distribution was 149 GG, 124 GT and 21 TT. With caloric restriction strategies, body weight, body mass index (BMI), fat mass, waist circumference, systolic blood pressure, total LDL cholesterol, LDL cholesterol and leptin levels decreased. Only in subjects with GG genotype, diet I and II decreased fasting insulin levels, HOMA-IR and adiponectin levels. The improvement was similar with both diets; insulin concentrations (Diet I: -4.7 ± 1.4 mUI/L vs. Diet II: -5.9 ± 1.9 mUI/L: p = .76), HOMA-IR (Diet I: -1.4 ± 0.6 units vs. Diet II: -2.0 ± 0.7 units: p = .56) and adiponectin levels (Diet I: -10.2 ± 3.4 ng/dl vs. Diet II: -14.0 ± 2.9 ng/dl: p = .33). The GG genotype of ADIPOQ gene variant (rs1501299) is associated with an increase in adiponectin levels and a decrease of insulin and HOMA-IR after weight loss. Copyright © 2018 Elsevier B.V. All rights reserved.

Adiponectin, in contrast to leptin, is not associated with body mass index, waist circumference and HOMA-IR in subjects of a west-African population.

PubMed

Awede, Bonaventure; Adovoekpe, Diane; Adehan, Grace; MacFarlane, Niall G; Azonbakin, Simon; Dossou, Emmanuel; Amoussou-Guenou, Marcellin; Djrolo, François

2018-06-01

Factors associated with plasma levels of adiponectin and leptin were studied in adult subjects without diabetes from Cotonou in Benin (West-Africa). Seventy (70) men and 45 women were included in the study. Anthropometric variables were measured and a venous blood sample was drawn from each subject, after an overnight fasting period, for measurement of plasma glucose, insulin, leptin, and adiponectin levels. HOMA-IR was determined to assess insulin resistance. Adiponectin and leptin levels were higher in women than in men (with adiponectin 18.48 ± 12.77 vs.7.8 ± 10.39 μg/mL, P < 0.0001, and leptin 30.77 ± 19.16 vs. 8.66 ± 8.24 ng/mL, P < 0.0001). Fasting insulin level and HOMA-IR were also higher in the females. Hyperleptinemia was observed in 66,96% of subjects and hypoadiponectinemia was present in 44.35% of subjects. In both men and women, leptin correlated with age (r = 0.2; P = 0.02), BMI (r = 0.572; P < 0.0001), waist circumference (r = 0.534; P < 0.0001), fasting insulin (r = 0.461; P < 0.001), and HOMA-IR (r = 0.430; P < 0.0001). No significant correlation was observed for adiponectin levels with these variables. Only in women, adiponectin was inversely correlated with fasting glucose (r = -0.423; P < 0.004). These data confirm previous descriptions of leptin but suggest that variations in factors determining serum adiponectin levels observed between ethnicities could also been seen between populations from the same ethnicity. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Deletion of AMPKα1 attenuates the anticontractile effect of perivascular adipose tissue (PVAT) and reduces adiponectin release.

PubMed

Almabrouk, Tarek A M; Ugusman, Azizah B; Katwan, Omar J; Salt, Ian P; Kennedy, Simon

2017-10-01

Perivascular adipose tissue (PVAT) surrounds most blood vessels and secretes numerous active substances, including adiponectin, which produce a net anticontractile effect in healthy individuals. AMPK is a key mediator of cellular energy balance and may mediate the vascular effects of adiponectin. In this study, we investigated the role of AMPK within PVAT in mediating the anticontractile effect of PVAT. Endothelium-denuded aortic rings from wild-type (WT; Sv129) and α 1 AMPK knockout (KO) mice were mounted on a wire myograph. Dose-response curves to the AMPK-independent vasodilator cromakalim were studied in vessels with and without PVAT, and effect of pre-incubation with conditioned media and adiponectin on relaxation was also studied. The effect of AMPKα1 KO on the secretory profile of PVAT was assessed by elisa. Thoracic aortic PVAT from KO mice was morphologically indistinct from that of WT and primarily composed of brown adipose tissue. PVAT augmented relaxation to cromakalim in WT but not KO aortic rings. Addition of WT PVAT augmented relaxation in KO aortic rings but KO PVAT had no effect in WT rings. PVAT from KO mice secreted significantly less adiponectin and addition of adiponectin to either KO or WT aortic rings without PVAT augmented relaxation to cromakalim. An adiponectin blocking peptide significantly attenuated relaxation in WT rings with PVAT but not in KO rings. AMPKα1 has a critical role in maintaining the anticontractile actions of PVAT; an effect independent of the endothelium but likely mediated through altered adiponectin secretion or sensitivity. This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc. © 2016 The British Pharmacological Society.

ADIPONECTIN IN AMNIOTIC FLUID IN NORMAL PREGNANCY, SPONTANEOUS LABOR AT TERM, AND PRETERM LABOR: A NOVEL ASSOCIATION WITH SUBCLINICAL INTRAUTERINE INFECTION/INFLAMMATION

PubMed Central

Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Kusanovic, Juan Pedro; Erez, Offer; Mittal, Pooja; Gotsch, Francesca; Chaiworapongsa, Tinnakorn; Than, Nandor Gabor; Kim, Sun Kwon; Pacora, Percy; Yeo, Lami; Dong, Zhong; Hassan, Sonia S.

2012-01-01

Objective Adiponectin, an anti-inflammatory and anti-diabetogenic adipokine, has an important regulatory effect on both the innate and adaptive limbs of the immune response. The objective of this study was to determine whether adiponectin is present in amniotic fluid (AF) and if its concentration changes with gestational age, in the presence of labor and in the presence of intra-amniotic infection (IAI) in patients with spontaneous preterm labor (PTL) and intact membranes. Study design This cross-sectional study included 468 patients in the following groups: 1) women in the mid-trimester of pregnancy (14–18 weeks) who underwent amniocentesis for genetic indications and delivered a normal neonate at term (n=52); 2) normal pregnant women at term with (n=49) and without (n=41) spontaneous labor; 3) patients with an episode of PTL and intact membranes who were classified into: a) PTL who delivered at term (n=149); b) PTL who delivered preterm (<37 weeks gestation) without IAI (n=108); and c) PTL with IAI (n=69) Adiponectin concentration in AF was determined by ELISA. Results 1) The median AF adiponectin concentration at term was significantly higher than in the mid-trimester (35.6 ng/mL, interquartile range [IQR] 26.4–52.7 vs. 29.9 ng/mL, IQR 19.9–35.2; p=0.01); 2) among women with PTL and intact membranes, the median amniotic fluid adiponectin concentration was significantly higher in patients with IAI than in those without IAI who delivered either at term (54.3 ng/mL, 39.0–91.8 vs. 50.1 ng/mL, 33.2–72.8; p = 0.02) or preterm (47.6 ng/mL, 32.6–74.6; p = 0.01); and 3) among women at term, there was no significant difference in the median amniotic fluid adiponectin concentration between those with and without labor (33.7 ng/mL, IQR 21.7–53.9 vs. 35.6 ng/mL IQR 26.4–52.7; respectively p=0.5). Conclusions 1) Adiponectin is a physiologic constituent of AF; and 2) adiponectin concentrations in AF are increased significantly with advancing gestation and in the presence of IAI. Collectively, these findings suggest that adiponectin plays a dynamic role in normal gestation and in the presence of IAI. PMID:19591073

Adiponectin levels are reduced, independent of polymorphisms in the adiponectin gene, after supplementation with alpha-linolenic acid among healthy adults.

PubMed

Nelson, Tracy L; Stevens, James R; Hickey, Matthew S

2007-09-01

Our first aim was to determine whether an isocaloric intervention using alpha-linolenic acid (ALA) in the form of flaxseed oil would alter adiponectin levels among overweight, otherwise healthy, males and females, and our second aim was to test for any potential modification of this intervention by 2 single nucleotide polymorphisms (276 and 45) in the adiponectin gene. Subjects included healthy adult males and females (approximately 81% female; average age, 38 years) with increased waist circumference (mean, 99 cm) and body mass index (mean, 30 kg/m(2)) who were free of chronic disease, not taking medications, and sedentary. Subjects met weekly with a registered dietician for 8 weeks. The control subjects (n = 27) were instructed not to alter their habitual diet and the ALA group (n = 30) was instructed to follow an enriched ALA diet by using flaxseed oil capsules (increasing ALA to 5% of total energy intake) and to lower their dietary fat consumption by a commensurate amount. Diets were analyzed using the Food Intake and Analysis System (v. 3.0, University of Texas School of Public Health, 1998). Fasting blood samples were obtained before and after the 8-week intervention. We found significant decreases (P = .02) in adiponectin (10.12 microg/mL pre, 9.23 microg/mL post) in the ALA group as compared with the control group (7.93 microg/mL pre, 8.10 microg/mL post) after the intervention. We also saw a decline in adiponectin in all genotype groups with the greatest decline among those carrying the rare T allele of single nucleotide polymorphism 276. There were no significant changes in fasting insulin, glucose, or quantitative insulin sensitivity check index values as a result of this intervention. In conclusion, this study suggests that supplementing with ALA for 8 weeks may lower adiponectin levels among healthy individuals, and this effect appears to be independent of polymorphisms in the adiponectin gene. Although the change in adiponectin in response to the omega-3 fatty acids was not accompanied by any change in glucose, insulin, or quantitative insulin sensitivity check index, long-term implications of such a decrease should be considered in future studies.

Structural and functional similarities between osmotin from Nicotiana tabacum seeds and human adiponectin.

PubMed

Miele, Marco; Costantini, Susan; Colonna, Giovanni

2011-02-02

Osmotin, a plant protein, specifically binds a seven transmembrane domain receptor-like protein to exert its biological activity via a RAS2/cAMP signaling pathway. The receptor protein is encoded in the gene ORE20/PHO36 and the mammalian homolog of PHO36 is a receptor for the human hormone adiponectin (ADIPOR1). Moreover it is known that the osmotin domain I can be overlapped to the β-barrel domain of adiponectin. Therefore, these observations and some already existing structural and biological data open a window on a possible use of the osmotin or of its derivative as adiponectin agonist. We have modelled the three-dimensional structure of the adiponectin trimer (ADIPOQ), and two ADIPOR1 and PHO36 receptors. Moreover, we have also modelled the following complexes: ADIPOQ/ADIPOR1, osmotin/PHO36 and osmotin/ADIPOR1. We have then shown the structural determinants of these interactions and their physico-chemical features and analyzed the related interaction residues involved in the formation of the complexes. The stability of the modelled structures and their complexes was always evaluated and controlled by molecular dynamics. On the basis of these results a 9 residues osmotin peptide was selected and its interaction with ADIPOR1 and PHO36 was modelled and analysed in term of energetic stability by molecular dynamics. To confirm in vivo the molecular modelling data, osmotin has been purified from nicotiana tabacum seeds and its nine residues peptide synthesized. We have used cultured human synovial fibroblasts that respond to adiponectin by increasing the expression of IL-6, TNF-alpha and IL-1beta via ADIPOR1. The biological effect on fibroblasts of osmotin and its peptide derivative has been found similar to that of adiponectin confirming the results found in silico.

Adiponectin Receptors Form Homomers and Heteromers Exhibiting Distinct Ligand Binding and Intracellular Signaling Properties*

PubMed Central

Almabouada, Farid; Diaz-Ruiz, Alberto; Rabanal-Ruiz, Yoana; Peinado, Juan R.; Vazquez-Martinez, Rafael; Malagon, Maria M.

2013-01-01

Adiponectin binds to two widely expressed receptors (AdipoR1 and AdipoR2) that contain seven transmembrane domains but, unlike G-protein coupled receptors, present an extracellular C terminus and a cytosolic N terminus. Recently, AdipoR1 was found to associate in high order complexes. However, it is still unknown whether AdipoR2 may also form homomers or heteromers with AdipoR1 or if such interactions may be functionally relevant. Herein, we have analyzed the oligomerization pattern of AdipoRs by FRET and immunoprecipitation and evaluated both the internalization of AdipoRs in response to various adiponectin isoforms and the effect of adiponectin binding to different AdipoR combinations on AMP-activated protein kinase phosphorylation and peroxisome proliferator-activated receptor α activation. Transfection of HEK293AD cells with AdipoR1 and AdipoR2 showed that both receptors colocalize at both the plasma membrane and the endoplasmic reticulum. Co-transfection with the different AdipoR pairs yielded high FRET efficiencies in non-stimulated cells, which indicates that AdipoR1 and AdipoR2 form homo- and heteromeric complexes under resting conditions. Live FRET imaging suggested that both homo- and heteromeric AdipoR complexes dissociate in response to adiponectin, but heteromers separate faster than homomers. Finally, phosphorylation of AMP-activated protein kinase in response to adiponectin was delayed in cells wherein heteromer formation was favored. In sum, our findings indicate that AdipoR1 and AdipoR2 form homo- and heteromers that present unique interaction behaviors and signaling properties. This raises the possibility that the pleiotropic, tissue-dependent functions of adiponectin depend on the expression levels of AdipoR1 and AdipoR2 and, therefore, on the steady-state proportion of homo- and heteromeric complexes. PMID:23255609

Compensation for obesity-induced insulin resistance in dogs: assessment of the effects of leptin, adiponectin, and glucagon-like peptide-1 using path analysis.

PubMed

Verkest, K R; Fleeman, L M; Morton, J M; Ishioka, K; Rand, J S

2011-07-01

The hormonal mediators of obesity-induced insulin resistance and compensatory hyperinsulinemia in dogs have not been identified. Plasma samples were obtained after a 24-h fast from 104 client-owned lean, overweight, and obese dogs. Plasma glucose and insulin concentrations were used to calculate insulin sensitivity and β-cell function with the use of the homeostasis model assessment (HOMA(insulin sensitivity) and HOMA(β-cell function), respectively). Path analysis with multivariable linear regression was used to identify whether fasting plasma leptin, adiponectin, or glucagon-like peptide-1 concentrations were associated with adiposity, insulin sensitivity, and basal insulin secretion. None of the dogs were hyperglycemic. In the final path model, adiposity was positively associated with leptin (P < 0.01) and glucagon-like peptide-1 (P = 0.04) concentrations. No significant total effect of adiposity on adiponectin in dogs (P = 0.24) was observed. If there is a direct effect of leptin on adiponectin, then our results indicate that this is a positive relationship, which at least partly counters a negative direct relationship between adiposity and adiponectin. Fasting plasma leptin concentration was directly negatively associated with fasting insulin sensitivity (P = 0.01) and positively associated with β-cell function (P < 0.01), but no direct association was observed between adiponectin concentration and either insulin sensitivity or β-cell function (P = 0.42 and 0.11, respectively). We conclude that dogs compensate effectively for obesity-induced insulin resistance. Fasting plasma leptin concentrations appear to be associated with obesity-associated changes in insulin sensitivity and compensatory hyperinsulinemia in naturally occurring obese dogs. Adiponectin does not appear to be involved in the pathophysiology of obesity-associated changes in insulin sensitivity. Copyright © 2011 Elsevier Inc. All rights reserved.

Visceral adiposity and high adiponectin levels are associated with the prevalence of pancreatic cystic lesions.

PubMed

Mizuno, Suguru; Nakai, Yousuke; Isayama, Hiroyuki; Yoshikawa, Takeharu; Saito, Kei; Takahara, Naminatsu; Kogure, Hirofumi; Tada, Minoru; Hayashi, Naoto; Koike, Kazuhiko

2018-05-17

Obesity is increasing in developed countries and is a risk factor for pancreatic cancer (PaC). We previously reported that obesity was associated with pancreatic cystic lesions (PCLs), which are both precursors of, and risk factors for, PaC. In the present study, we further investigated the relationship between visceral adiposity and adiponectin levels and the extent of PCLs. Individuals who underwent comprehensive health screening at our institution between January 2008 and March 2013 were analyzed. PCLs were diagnosed via magnetic resonance imaging using a 3.0 Tesla system. The volumes of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured from computed tomographic volume data. Serum levels of adiponectin were measured using a sandwich enzyme-linked immunosorbent assay. The prevalences of PCLs were 14.2% in males (N = 2683; mean age, 56.4 years) and 16.2% in females (N = 1741; mean age, 57.1 years). The prevalence of PCLs increased gradually as VAT volume increased (P < 0.001). PCLs were more prevalent in individuals with high adiponectin levels (18.7% vs. 13.8%, P = 0.005). VAT volume (odds ratio [OR] for the highest quartiles, 1.52 [1.07-2.16]; P = 0.025) and adiponectin level (OR for the highest quartiles, 1.31 [1.08-1.59]; P = 0.007) but not SAT volume (P = 0.828) was significantly associated with PCLs in multivariate analyses. Visceral adiposity and high adiponectin levels were associated with PCL prevalence. Further work is needed to explore the relationships between visceral adiposity and adiponectin levels, and PCLs and PaC.

Plasma Levels of Fatty Acid-Binding Protein 4, Retinol-Binding Protein 4, High-Molecular Weight Adiponectin, and Cardiovascular Mortality among Men with Type 2 Diabetes: A 22-Year Prospective Study

PubMed Central

Liu, Gang; Ding, Ming; Chiuve, Stephanie E.; Rimm, Eric B.; Franks, Paul W.; Meigs, James B.; Hu, Frank B.; Sun, Qi

2016-01-01

Objective To examine select adipokines, including fatty acid-binding protein 4 (FABP4), retinol-binding protein 4 (RBP4), and high-molecular weight (HMW) adiponectin in relation to cardiovascular disease (CVD) mortality among patients with type 2 diabetes (T2D). Approach and Results Plasma levels of FABP4, RBP4, and HMW adiponectin were measured in 950 men with T2D in the Health Professionals Follow-up Study. After an average of 22 years of follow up (1993–2015), 580 deaths occurred, of whom 220 died of CVD. After multivariate adjustment for covariates, higher levels of FABP4 were significantly associated with a higher CVD mortality: comparing extreme tertiles, the hazard ratio (HR) and 95% confidence interval (CI) of CVD mortality was 1.78 (1.22, 2.59; P trend=0.001). A positive association was also observed for HMW adiponectin: the HR (95% CI) was 2.07 (1.42, 3.06; P trend=0.0002), comparing extreme tertiles, whereas higher RBP4 levels were non-significantly associated with a decreased CVD mortality with an HR (95% CI) of 0.73 (0.50, 1.07; P trend=0.09). A Mendelian randomization (MR) analysis suggested that the causal relationships of HMW adiponectin and RBP4 would be directionally opposite to those observed based on the biomarkers, although none of the MR associations achieved statistical significance. Conclusions These data suggest that higher levels of FABP4 and HMW adiponectin are associated with elevated CVD mortality among men with T2D. Biological mechanisms underlying these observations deserve elucidation, but the associations of HMW adiponectin may partially reflect altered adipose tissue functionality among T2D patients. PMID:27609367

Development of second generation peptides modulating cellular adiponectin receptor responses

NASA Astrophysics Data System (ADS)

Otvos, Laszlo; Knappe, Daniel; Hoffmann, Ralf; Kovalszky, Ilona; Olah, Julia; Hewitson, Tim; Stawikowska, Roma; Stawikowski, Maciej; Cudic, Predrag; Lin, Feng; Wade, John; Surmacz, Eva; Lovas, Sandor

2014-10-01

The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC). In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML) cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399). The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM - low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400) was designed that counteracted 10-1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400) at similar concentrations will be an important target validation tool to study adiponectin functions.

Stinging Nettle (Urtica dioica L.) Attenuates FFA Induced Ceramide Accumulation in 3T3-L1 Adipocytes in an Adiponectin Dependent Manner.

PubMed

Obanda, Diana N; Zhao, Peng; Richard, Allison J; Ribnicky, David; Cefalu, William T; Stephens, Jacqueline M

2016-01-01

Excess dietary lipids result in the accumulation of lipid metabolites including ceramides that can attenuate insulin signaling. There is evidence that a botanical extract of Urtica dioica L. (stinging nettle) improves insulin action, yet the precise mechanism(s) are not known. Hence, we examined the effects of Urtica dioica L. (UT) on adipocytes. We investigated the effects of an ethanolic extract of UT on free fatty acid (palmitic acid) induced inhibition of insulin-stimulated Akt serine phosphorylation and modulation of ceramidase expression in 3T3-L1 adipocytes. Adipocytes were exposed to excess FFAs in the presence or absence of UT. Effects on adiponectin expression, ceramidase expression, ceramidase activity, ceramide accumulation and insulin signaling were determined. As expected, FFAs reduced adiponectin expression and increased the expression of ceramidase enzymes but not their activity. FFA also induced the accumulation of ceramides and reduced insulin-stimulated phosphorylation of Akt in adipocytes. The effects of FFA were partially reversed by UT. UT enhanced adiponectin expression and ceramidase activity in the presence of excess FFAs. UT abated ceramide accumulation and increased insulin sensitivity via enhanced Akt phosphorylation. A siRNA knockdown of adiponectin expression prevented UT from exerting positive effects on ceramidase activity but not Akt phosphorylation. In adipocytes, the ability of UT to antagonize the negative effects of FFA by modulating ceramidase activity and ceramide accumulation is dependent on the presence of adiponectin. However, the ability of UT to enhance Akt phosphorylation is independent of adiponectin expression. These studies demonstrate direct effects of UT on adipocytes and suggest this botanical extract is metabolically beneficial.

Adiponectin Levels and Longitudinal Changes in Metabolic Syndrome: The Healthy Twin Study.

PubMed

Song, Yun-Mi; Lee, Kayoung; Sung, Joohon

2015-09-01

We investigated the association of plasma adiponectin levels with longitudinal changes in metabolic syndrome and the metabolic syndrome-related traits [insulin and homeostasis model assessment of insulin resistance (HOMA-IR)], as well as their genetic and environmental correlations. A total of 1030 Koreans (380 men and 650 women; 44.0 ± 12.7 years old) without diabetes of the Healthy Twin Study visited at baseline (2005-2010) and returned for a follow-up examination 3.7 ± 1.2 years later. Baseline plasma adiponectin, metabolic syndrome components [waist circumference (WC), glucose, blood pressure, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs)] and metabolic syndrome-related traits were measured at baseline and follow-up. After adjusting for age, sex, smoking, alcohol consumption, physical activity, caloric intake, education level, body mass index (BMI), family history of diabetes, and changes in BMI, 1 standard deviation increment in baseline adiponectin levels was associated with 38-63% lower odds of incident and persistent metabolic syndrome. After additionally adjusting for the baseline levels of each trait, baseline adiponectin levels were inversely associated with WC, blood pressure, insulin, HOMA-IR, and TGs values at follow-up. After adjusting for age, sex, and baseline values of each trait or sum of metabolic syndrome components, baseline adiponectin levels exhibited significantly inverse genetic and environmental correlations with insulin, HOMA-IR, and HDL-C values and the sum of metabolic syndrome components at follow-up. High adiponectin levels reduce the risk of developing metabolic syndrome and having persistent metabolic syndrome and increase of metabolic syndrome-related traits over time. These associations may be explained by pleiotropic genetic mechanisms.

Oral administration of γ-aminobutyric acid and γ-oryzanol prevents stress-induced hypoadiponectinemia.

PubMed

Ohara, Kazuyuki; Kiyotani, Yuka; Uchida, Asako; Nagasaka, Reiko; Maehara, Hiroyuki; Kanemoto, Shigeharu; Hori, Masatoshi; Ushio, Hideki

2011-06-15

Metabolic syndrome is a cluster of risk factors including insulin resistance and type 2 diabetes and is found to associate partly with chronic stress at work in human. Adiponectin circulates in mammal blood mainly as a low molecular weight (LMW) trimer, hexamer, and a high molecular weight (HMW) multimers. Low circulating levels of adiponectin are related to metabolic syndrome. We have then investigated the influence of immobilization stress on plasma adiponectin concentrations in mice. Relative LMW and HMW adiponectin levels were markedly reduced by immobilization stress (0.66±0.07 and 0.59±0.06 after 102 h, respectively), significantly different from the control values (p<0.01 and 0.05, respectively). γ-Aminobutyric acid (GABA) and γ-oryzanol abundantly contained in germinated brown rice have some physiological functions. We further investigated the effect of GABA, γ-oryzanol, GABA plus γ-oryzanol on adiponectin levels in mice subjected to immobilization stress. GABA and γ-oryzanol significantly increased the relative LMW and HMW adiponectin levels under immobilization stress (1.10±0.11 and 0.99±0.19 after 102 h, respectively, for GABA; 1.08±0.17 and 1.15±0.17 after 102 h, respectively, for γ-oryzanol). Additionally, the co-administration of GABA and γ-oryzanol also increased both relative LMW and HMW adiponectin levels (1.02±0.07 and 0.99±0.10 after 102 h, respectively) and was effective in an earlier phase from 30 to 54 h. The results indicate that the co-administration of GABA and γ-oryzanol might be effective in preventing stress-induced hypoadiponectinemia in mice and be also a promising tool for improving metabolic syndrome aggravated by chronic stress. Copyright © 2011 Elsevier GmbH. All rights reserved.

Adiponectin receptors form homomers and heteromers exhibiting distinct ligand binding and intracellular signaling properties.

PubMed

Almabouada, Farid; Diaz-Ruiz, Alberto; Rabanal-Ruiz, Yoana; Peinado, Juan R; Vazquez-Martinez, Rafael; Malagon, Maria M

2013-02-01

Adiponectin binds to two widely expressed receptors (AdipoR1 and AdipoR2) that contain seven transmembrane domains but, unlike G-protein coupled receptors, present an extracellular C terminus and a cytosolic N terminus. Recently, AdipoR1 was found to associate in high order complexes. However, it is still unknown whether AdipoR2 may also form homomers or heteromers with AdipoR1 or if such interactions may be functionally relevant. Herein, we have analyzed the oligomerization pattern of AdipoRs by FRET and immunoprecipitation and evaluated both the internalization of AdipoRs in response to various adiponectin isoforms and the effect of adiponectin binding to different AdipoR combinations on AMP-activated protein kinase phosphorylation and peroxisome proliferator-activated receptor α activation. Transfection of HEK293AD cells with AdipoR1 and AdipoR2 showed that both receptors colocalize at both the plasma membrane and the endoplasmic reticulum. Co-transfection with the different AdipoR pairs yielded high FRET efficiencies in non-stimulated cells, which indicates that AdipoR1 and AdipoR2 form homo- and heteromeric complexes under resting conditions. Live FRET imaging suggested that both homo- and heteromeric AdipoR complexes dissociate in response to adiponectin, but heteromers separate faster than homomers. Finally, phosphorylation of AMP-activated protein kinase in response to adiponectin was delayed in cells wherein heteromer formation was favored. In sum, our findings indicate that AdipoR1 and AdipoR2 form homo- and heteromers that present unique interaction behaviors and signaling properties. This raises the possibility that the pleiotropic, tissue-dependent functions of adiponectin depend on the expression levels of AdipoR1 and AdipoR2 and, therefore, on the steady-state proportion of homo- and heteromeric complexes.

Sex dimorphism in late gestational sleep fragmentation and metabolic dysfunction in offspring mice.

PubMed

Khalyfa, Abdelnaby; Carreras, Alba; Almendros, Isaac; Hakim, Fahed; Gozal, David

2015-04-01

Excessive sleep fragmentation (SF) is common in pregnant women. Adult-onset metabolic disorders may begin during early development and exhibit substantial sex dimorphism. We hypothesized that metabolic dysfunction induced by gestational SF in male mice would not be apparent in female littermates. Body weight and food consumption were measured weekly in male and female offspring after late gestational SF or control sleep (SC). At 20 weeks, plasma leptin, adiponectin, lipid profiles, and insulin and glucose tolerance tests were assessed. Leptin and adiponectin, M1, and M2 macrophage messenger RNA expression and polarity were examined. Adiponectin gene promoter methylation levels in several tissues were assessed. Food intake, body weight, visceral fat mass, and insulin resistance were higher, and adiponectin levels lower in male but not female offspring exposed to gestational SF. However, dyslipidemia was apparent in both male and female offspring exposed to SF, albeit of lesser magnitude. In visceral fat, leptin messenger RNA expression was selectively increased and adiponectin expression was decreased in male offspring exposed to gestational SF, but adiponectin was increased in exposed female offspring. Differences in adipokine expression also emerged in liver, subcutaneous fat, and muscle. Increased M1 macrophage markers were present in male offspring exposed to SF (SFOM) while increased M2 markers emerged in SF in female offspring (SFOF). Similarly, significant differences emerged in the methylation patterns of adiponectin promoter in SFOM and SFOF. Gestational sleep fragmentation increases the susceptibility to obesity and metabolic syndrome in male but not in female offspring, most likely via epigenetic changes. Thus, sleep perturbations impose long-term detrimental effects to the fetus manifesting as sex dimorphic metabolic dysfunction in adulthood. © 2015 Associated Professional Sleep Societies, LLC.

Stinging Nettle (Urtica dioica L.) Attenuates FFA Induced Ceramide Accumulation in 3T3-L1 Adipocytes in an Adiponectin Dependent Manner

PubMed Central

Obanda, Diana N.; Zhao, Peng; Richard, Allison J.; Ribnicky, David; Cefalu, William T.; Stephens, Jacqueline M.

2016-01-01

Objective Excess dietary lipids result in the accumulation of lipid metabolites including ceramides that can attenuate insulin signaling. There is evidence that a botanical extract of Urtica dioica L. (stinging nettle) improves insulin action, yet the precise mechanism(s) are not known. Hence, we examined the effects of Urtica dioica L. (UT) on adipocytes. Research Design We investigated the effects of an ethanolic extract of UT on free fatty acid (palmitic acid) induced inhibition of insulin-stimulated Akt serine phosphorylation and modulation of ceramidase expression in 3T3-L1 adipocytes. Adipocytes were exposed to excess FFAs in the presence or absence of UT. Effects on adiponectin expression, ceramidase expression, ceramidase activity, ceramide accumulation and insulin signaling were determined. Results As expected, FFAs reduced adiponectin expression and increased the expression of ceramidase enzymes but not their activity. FFA also induced the accumulation of ceramides and reduced insulin-stimulated phosphorylation of Akt in adipocytes. The effects of FFA were partially reversed by UT. UT enhanced adiponectin expression and ceramidase activity in the presence of excess FFAs. UT abated ceramide accumulation and increased insulin sensitivity via enhanced Akt phosphorylation. A siRNA knockdown of adiponectin expression prevented UT from exerting positive effects on ceramidase activity but not Akt phosphorylation. Conclusions In adipocytes, the ability of UT to antagonize the negative effects of FFA by modulating ceramidase activity and ceramide accumulation is dependent on the presence of adiponectin. However, the ability of UT to enhance Akt phosphorylation is independent of adiponectin expression. These studies demonstrate direct effects of UT on adipocytes and suggest this botanical extract is metabolically beneficial. PMID:26939068

Accumulation of subcutaneous fat, but not visceral fat, is a predictor of adiponectin levels in preterm infants at term-equivalent age.

PubMed

Nakano, Yuya; Itabashi, Kazuo; Sakurai, Motoichiro; Aizawa, Madoka; Dobashi, Kazushige; Mizuno, Katsumi

2014-05-01

Preterm infants have altered fat tissue development, including a higher percentage of fat mass and increased volume of visceral fat. They also have altered adiponectin levels, including a lower ratio of high-molecular-weight adiponectin (HMW-Ad) to total adiponectin (T-Ad) at term-equivalent age, compared with term infants. The objective of this study was to investigate the association between adiponectin levels and fat tissue accumulation or distribution in preterm infants at term-equivalent age. Cross-sectional clinical study. Study subjects were 53 preterm infants born at ≤34weeks gestation with a mean birth weight of 1592g. Serum levels of T-Ad and HMW-Ad were measured and a computed tomography (CT) scan was performed at the level of the umbilicus at term-equivalent age to analyze how fat tissue accumulation or distribution was correlated with adiponectin levels. T-Ad (r=0.315, p=0.022) and HMW-Ad levels (r=0.338, p=0.013) were positively associated with subcutaneous fat area evaluated by performing CT scan at term-equivalent age, but were not associated with visceral fat area in simple regression analyses. In addition, T-Ad (β=0.487, p=0.003) and HMW-Ad levels (β=0.602, p<0.001) were positively associated with subcutaneous fat tissue area, but they were not associated with visceral fat area also in multiple regression analyses. Subcutaneous fat accumulation contributes to increased levels of T-Ad and HMW-Ad, while visceral fat accumulation does not influence adiponectin levels in preterm infants at term-equivalent age. Copyright © 2014 Elsevier Ltd. All rights reserved.

Disturbed adiponectin – AMPK system in skeletal muscle of patients with metabolic syndrome.

PubMed

Van Berendoncks, An M; Stensvold, Dorthe; Garnier, Anne; Fortin, Dominique; Sente, Tahnee; Vrints, Christiaan J; Arild, Slørdahl Stig; Ventura-Clapier, Renee; Wisløff, Ulrik; Conraads, Viviane M

2015-02-01

Patients with metabolic syndrome are characterized by low circulating adiponectin levels and reduced adiponectin sensitivity in skeletal muscles. Through binding on its main skeletal muscle receptor AdipoR1, adiponectin activates AMP-activated protein kinase (AMPK), a key player in energy homeostasis. Fourteen metabolic syndrome patients and seven healthy control subjects were included. Blood samples were taken to determine insulin resistance, adiponectin, lipoproteins, and C-reactive protein. Muscle biopsies (m. vastus lateralis) were obtained to assess mRNA expression of AdipoR1 and both AMPKα1 and AMPKα2 subunits, as well as downstream targets in lipid and glucose metabolism. Skeletal muscle mRNA expression of AMPKα1 and AMPKα2 was lower in metabolic syndrome patients (100 ± 6 vs. 122 ± 8 AU, p = 0.030 and 64 ± 4 vs. 85 ± 9 AU, p = 0.044, respectively), whereas the expression of AdipoR1 was upregulated (138 ± 9 vs. 105 ± 7, p = 0.012). AMPKα1 and AdipoR1 correlated positively in both the control (r = 0.964, p < 0.001) and the metabolic syndrome group (r = 0.600, p = 0.023). However, this relation was shifted upwards in metabolic syndrome patients, indicating increased AdipoR1mRNA expression for a similar AMPKα1 expression. Previously, a blunted stimulatory effect of adiponectin on AMPK activation has been shown in metabolic syndrome patients. The present data suggest that the disturbed interaction of adiponectin with AMPK is located downstream of the AdipoR1 receptor. © The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Two-year changes in circulating adiponectin, ectopic fat distribution and body composition in response to weight-loss diets: the POUNDS Lost Trial.

PubMed

Ma, W; Huang, T; Wang, M; Zheng, Y; Wang, T; Heianza, Y; Sun, D; Smith, S R; Bray, G A; Sacks, F M; Qi, L

2016-11-01

Adiponectin has a pivotal role in linking fat distribution with cardiometabolic disorders. We investigated the associations of long-term changes in circulating adiponectin with body composition and fat distribution at different abdominal depots in response to weight-loss dietary interventions, as well as the modification effect of sex. In the 2-year Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) Trial, 811 overweight or obese adults were randomly assigned to one of four diets varying in macronutrient intakes. Circulating concentrations of adiponectin were repeatedly measured at baseline, 6 months and 2 years. Body composition and fat distribution were repeatedly measured by dual-energy X-ray absorptiometry scan (n=424) and computed tomography (n=195). Over the 2-year intervention, after adjustment for age, sex, ethnicity, follow-up time, diet group, baseline body mass index and baseline level of respective outcome trait, increase of adiponectin was significantly associated with reduction of total fat mass (FM), total fat-free mass (FFM), whole body total percentage of fat mass (FM%), percentage of trunk fat (TF%), total adipose tissue (TAT), and adipose tissue mass at different depots including visceral (VAT), deep subcutaneous (DSAT) and superficial subcutaneous (SSAT; P<0.03 for each). The relations with FM, FM%, TF%, VAT and DSAT were significantly modified by sex (P for interaction=0.02, 0.005 and <0.001, 0.002, 0.03, respectively) with greater reductions associated with increase of adiponectin in men than in women. Long-term changes in circulating adiponectin were differentially associated with improvement of body composition and abdominal fat distribution in men and women.

Association of ADIPOQ gene with obesity and adiponectin levels in Malaysian Malays.

PubMed

Apalasamy, Yamunah Devi; Rampal, Sanjay; Salim, Agus; Moy, Foong Ming; Bulgiba, Awang; Mohamed, Zahurin

2014-05-01

Studies have shown that single-nucleotide polymorphisms (SNPs) on the ADIPOQ gene have been linked with obesity and with adiponectin levels in various populations. Here, we aimed to investigate the association of ADIPOQ rs17366568 and rs3774261 SNPs with obesity and with adiponectin levels in Malaysian Malays. Obesity parameters and adiponectin levels were measured in 574 subjects. Genotyping was performed using real-time polymerase chain reaction and Sequenom MassARRAY. A significant genotypic association was observed between ADIPOQ rs17366568 and obesity. The frequencies of AG and AA genotypes were significantly higher in the obese group (11%) than in the non-obese group (5%) (P=0.024). The odds of A alleles occurring among the obese group were twice those among the non-obese group (odds ratio 2.15; 95% confidence interval 1.13-4.09). However, no significant association was found between allelic frequencies of ADIPOQ rs17366568 and obesity after Bonferroni correction (P>0.025) or between ADIPOQ rs3774261 and obesity both at allelic and genotypic levels. ADIPOQ SNPs were not significantly associated with log-adiponectin levels. GA, GG, and AG haplotypes of the ADIPOQ gene were not associated with obesity. We confirmed the previously reported association of ADIPOQ rs17366568 with the risk of obesity. ADIPOQ SNPs are not important modulators of adiponectin levels in this population.

Leukocyte Telomere Length and Serum Levels of High-Molecular-Weight Adiponectin and Dehydroepiandrosterone-Sulfate Could Reflect Distinct Aspects of Longevity in Japanese Centenarians.

PubMed

Aoki, Yuji; Aoki, Masato; Yamada, Kazuya

2017-01-01

Leukocyte telomere length and serum levels of high-molecular-weight adiponectin and dehydroepiandrosterone-sulfate (DHEA-S) were assessed in association with nutrition and performance status (PS) in Japanese centenarians. Twenty-three centenarians (five men, 18 women) were classified according to their PS 1 (nearly fully ambulatory, n = 2), 2 (in bed less than 50% of daytime, n = 10), 3 (in bed greater than 50%, n = 6), and 4 (completely bedridden, n = 5). Leukocyte telomere length was determined by the hybridization protection assay, and the adiponectin and DHEA-S levels were measured by chemiluminescent enzyme immunoassay. Among variables of PS, body mass index (BMI), albumin, adiponectin, DHEA-S, and telomere length, there were significant correlations between PS and albumin ( r = -.694, p < .01), between telomere length and BMI ( r = .522, p < .05), between adiponectin and BMI ( r = -.574, p < .01), and between DHEA-S and albumin ( r = .530, p < .01). When excluding two cancer-bearing centenarians with short telomere, telomere length significantly correlated with PS ( r = -.632, p < .01). It was indicated that the short leukocyte telomere was associated with poor PS and cancer development and that the adiponectin or DHEA-S was associated with adiposity or nutritional status. Despite a small number of subjects, these biomarkers seemed to reflect distinct aspects of longevity in Japanese centenarians.

Relationship Between Retinal Blood Flow and Serum Adiponectin Concentrations in Patients With Type 2 Diabetes Mellitus.

PubMed

Omae, Tsuneaki; Nagaoka, Taiji; Yoshida, Akitoshi

2015-06-01

To study the relationship between retinal microcirculation and serum adiponectin, an important adipocytokine secreted by adipocytes, concentrations in patients with type 2 diabetes mellitus. Using a laser Doppler velocimetry system, we simultaneously measured the retinal blood flow (RBF) values and retinal vessel diameter and blood velocity in 64 consecutive Japanese patients (mean age ± SD, 59.8 ± 10.4 years) with type 2 diabetes with no or mild nonproliferative diabetic retinopathy. We compared the values with the RBF and serum adiponectin concentrations in these patients. The patients were divided into two groups based on sex (33 males, 31 females). The plasma adiponectin concentrations were correlated positively with the retinal vessel diameter (r = 0.480; P = 0.005), retinal blood velocity (r = 0.399; P = 0.02), and RBF (r = 0.518; P = 0.002) and correlated negatively with the retinal arterial vascular resistance (r = -0.598; P = 0.0002) in males, but not females, with type 2 diabetes with early-stage diabetic retinopathy. Multiple regression analysis showed that the plasma adiponectin level was independently and positively correlated with RBF and negatively correlated with retinal arterial vascular resistance. Our results indicated that a high concentration of serum adiponectin may be associated with increased RBF, probably via the increased blood velocity and dilated vessel diameter in males with type 2 diabetes with early-phase diabetic retinopathy.

Elevated Adiponectin Serum Levels in Women with Systemic Autoimmune Diseases

PubMed Central

Toussirot, Éric; Gaugler, Béatrice; Bouhaddi, Malika; Nguyen, Nhu Uyen; Saas, Philippe; Dumoulin, Gilles

2010-01-01

Adipose tissue produces a wide range of proteins that may influence the immune system. In this study, we assessed the serum levels of leptin, adiponectin, and ghrelin, in association with the measurements of body composition, in 15 female patients with various autoimmune diseases (systemic lupus erythematosus, primary Sjögren's syndrome, sarcoidosis, mixed connective tissue disease, vasculitis, CREST syndrome, and polymyositis) and in 15 healthy female controls. There were no statistically significant differences between the patients and controls with regard to serum leptin, serum ghrelin, global fat mass, adiposity, and fat mass in the android or gynoid regions, whereas serum adiponectin levels were higher in patients than controls (16.3 ± 1.6 μg/mL versus 9.7 ± 0.6 μg/mL; P = .01). As adiponectin is known to exhibit potent anti-inflammatory properties, a high adiponectinemia in patients with systemic autoimmune disease may mitigate the inflammatory response. However, the precise consequences of these elevated serum adiponectin levels on the metabolic syndrome development and atherosclerotic cardiovascular risk in this patient population still needs to be determined. PMID:21234350

Does dietary iodine regulate oxidative stress and adiponectin levels in human breast milk?

PubMed

Gutiérrez-Repiso, Carolina; Velasco, Inés; Garcia-Escobar, Eva; Garcia-Serrano, Sara; Rodríguez-Pacheco, Francisca; Linares, Francisca; Ruiz de Adana, Maria Soledad; Rubio-Martin, Elehazara; Garrido-Sanchez, Lourdes; Cobos-Bravo, Juan Francisco; Priego-Puga, Tatiana; Rojo-Martinez, Gemma; Soriguer, Federico; García-Fuentes, Eduardo

2014-02-10

Little is known about the association between iodine and human milk composition. In this study, we investigated the association between iodine and different markers of oxidative stress and obesity-related hormones in human breast milk. This work is composed of two cross-sectional studies (in lactating women and in the general population), one prospective and one in vitro. In the cross-sectional study in lactating women, the breast milk iodine correlated negatively with superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) activities, and with adiponectin levels. An in vitro culture of human adipocytes with 1 μM potassium iodide (KI, dose similar to the human breast milk iodine concentration) produced a significant decrease in adiponectin, GSH-Px, SOD1, and SOD2 mRNA expression. However, after 2 months of treatment with KI in the prospective study, a positive correlation was found between 24-h urinary iodine and serum adiponectin. Our observations lead to the hypothesis that iodine may be a factor directly involved in the regulation of oxidative stress and adiponectin levels in human breast milk.

The impact of follicular fluid adiponectin and ghrelin levels based on BMI on IVF outcomes in PCOS.

PubMed

Inal, H A; Yilmaz, N; Gorkem, U; Oruc, A S; Timur, H

2016-04-01

This study aimed at evaluating the effects of polycystic ovary syndrome (PCOS) and body mass index (BMI) on follicular fluid (FF) adiponectin and ghrelin levels, and on in vitro fertilization outcomes in patients who underwent controlled ovarian hyperstimulation. This prospective cross-sectional study was performed with a total of 120 primary infertile women [group 1; non-PCOS = 60 (BMI <25 = 30, BMI ≥25 = 30) and group 2; PCOS = 60 (BMI <25 = 30, BMI ≥25 = 30)]. On the day of oocyte pickup, FF samples were collected. The FF adiponectin levels were lower in the lean PCOS group than the lean non-PCOS group (p = 0.001), and these levels were lower in the overweight non-PCOS group compared to lean non-PCOS group (0.001). However, there was no difference in the FF ghrelin levels between the groups. Additionally, we could not find a relationship between clinical pregnancy and adiponectin and ghrelin levels. The FF adiponectin and ghrelin levels have no effects on clinical pregnancy in PCOS. Therefore, further studies are needed to elucidate this issue.

Comparison of cytokines and prooxidants/antioxidants markers among adults with refractory versus well-controlled epilepsy: A cross-sectional study.

PubMed

Ethemoglu, Ozlem; Ay, Halil; Koyuncu, Ismail; Gönel, Ataman

2018-06-15

This study aims to investigate the serum adiponectin, interleukin (IL)-6 and oxidative stress in epilepsy patients who are refractory or non-refractory to treatments. The study comprised 31 refractory epilepsy, 29 well-controlled epilepsy patients and control group including 29 healthy individuals. The serum adiponectin, IL-6, total antioxidant status (TAS), total oxidant status levels (TOS) and oxidative stress index (OSİ) were determined. The mean serum adiponectin and TAS levels were significantly lower in the refractory epilepsy patients than in the healty controls, and mean IL-6, TOS and OSİ levels were significantly higher. The serum adiponectin, IL-6, TAS, TOS and OSI levels were not significantly different between the well-controlled epilepsy patients and the healthy controls. The mean serum IL-6 and oxidative stress levels in refractory epilepsy patients were higher and the serum adiponectin level was lower than the healthy control group. These findings may be associated with an increased risk of seizures, atherosclerosis and cardiovascular disease in refractory epilepsy patients. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Roles of leptin, adiponectin and resistin in the transcriptional regulation of steroidogenic genes contributing to decreased Leydig cells function in obesity.

PubMed

Roumaud, Pauline; Martin, Luc J

2015-10-01

The increase in obesity rate is a major public health issue associated with increased pathological conditions such as type 2 diabetes or cardiovascular diseases. Obesity also contributes to decreased testosterone levels in men. Indeed, the adipose tissue is an endocrine organ which produces hormones such as leptin, adiponectin and resistin. Obesity results in pathological accumulations of leptin and resistin, whereas adiponectin plasma levels are markedly reduced, all having a negative impact on testosterone synthesis. This review focuses on current knowledge related to transcriptional regulation of Leydig cells' steroidogenesis by leptin, adiponectin and resistin. We show that there are crosstalks between the regulatory mechanisms of these hormones and androgen production which may result in a dramatic negative influence on testosterone plasma levels. Indeed leptin, adiponectin and resistin can impact expression of different steroidogenic genes such as Star, Cyp11a1 or Sf1. Further investigations will be required to better define the implications of adipose derived hormones on regulation of steroidogenic genes expression within Leydig cells under physiological as well as pathological conditions.

Serum adiponectin and resistin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome.

PubMed

Pangaribuan, Bertha; Yusuf, Irawan; Mansyur, Muchtaruddin; Wijaya, Andi

2011-12-01

The role of insulin resistance in polycystic ovary syndrome (PCOS) has been established. However the role of adiponectin and resistin in the relationship between insulin resistance as markers of obesity and PCOS has not been conclusive. This study aims to determine the influence of the serum levels of adiponectin and resistin on PCOS, and assess possible correlations with the hormonal and metabolic parameters of the syndrome and obesity. This study continued a case control study that had finished recruiting 24 subjects of reproductive women with PCOS as a case group, and 24 subjects of normal ovulatory reproductive women without hyperandrogenism as a control group. Further, only 18 subjects of the control group had a body mass index (BMI) <25 kg/m(2) and were included the data analysis, whereas others were excluded. Therefore, these study data were divided into three groups. Twenty-four PCOS patients from the case group were allocated to two groups, A (n = 14) patients had PCOS + BMI ≥25 kg/m(2); B (n = 10) patients had PCOS + BMI <25 kg/m(2). Group C was the control group of 18 reproductive women without PCOS + BMI <25 kg/m(2). Blood samples were collected between day 3 and 5 of a spontaneous menstrual cycle, at 07:00 to 09:00, after overnight fasting. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, prolactin, sex hormone-binding globulin (SHBG), glucose, insulin, adiponectin and resistin were measured. Serum adiponectin levels were significantly decreased in group A compared with group B and group C. No significant difference existed in adiponectin between group B and group C. Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR) value in group A was found to be significantly higher than group C, but no significant differences were found between group B and group C or between group A and group B. There was no significant difference in serum resistin between all groups, nevertheless the resistin-to-adiponectin (R:A) ratio was significantly decreased in group A compared with groups B and C. In a multiple regression model, BMI, testosterone and insulin resistance were the major determinants of hypoadiponectinemia. However, only BMI was the major determinant of the resistin represented by the R:A ratio. Serum adiponectin levels and the ratio of resistin to adiponectin levels are reduced in obese women with PCOS. These results suggest that, by reducing adiponectin serum level, hyperandrogenemia, together with nutritional status of obesity, might contribute to insulin resistance in the pathogenesis of PCOS.

Serum adiponectin helps to differentiate type 1 and type 2 diabetes among young Asian Indians.

PubMed

Gokulakrishnan, Kuppan; Aravindhan, Vivekanandhan; Amutha, Anandakumar; Abhijit, Shiny; Ranjani, Harish; Anjana, Ranjit Mohan; Unnikrishnan, Ranjith; Miranda, Priya; Narayan, K M Venkat; Mohan, Viswanathan

2013-08-01

This study assessed whether serum adiponectin could be used as a biochemical marker to differentiate type 1 diabetes mellitus (T1DM) from type 2 diabetes mellitus (T2DM) among young Asian Indians. We recruited age- and sex-matched individuals with physician-diagnosed T1DM (n=70) and T2DM (n=72). All were 12-27 years of age with a duration of diabetes of >2 years, at a large tertiary-care diabetes center in Chennai, southern India. Age- and sex-matched individuals with normal glucose tolerance (NGT) (n=68) were selected from an ongoing population study. NGT was defined using World Health Organization criteria. Serum total adiponectin was measured by enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curves were used to identify adiponectin cut points for discriminating T1DM from T2DM. Adiponectin levels were higher in T1DM and lower in T2DM compared with the NGT group (9.89, 3.88, and 6.84 μg/mL, respectively; P<0.001). In standardized polytomous regression models, adiponectin was associated with T1DM (odds ratio [OR]=1.131 per SD; 95% confidence interval [CI], 1.025-1.249) and T2DM (OR=0.628 per SD; 95% CI, 0.504-0.721) controlled for age, gender, waist circumference, body mass index, hypertension, glycated hemoglobin, total cholesterol, serum triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, family history of T2DM, and estimated glomerular filtration rate. Using ROC analysis, an adiponectin cut point of 5.1 μg/mL had a C statistic of 0.886 (95% CI, 0.836-0.953), sensitivity of 80.6%, and specificity of 80.6% to differentiate T1DM from T2DM. Using the 5.1 μg/mL cut point, 80.6% of T1DM and 81.8% of T2DM would be correctly classified. Serum adiponectin is a useful biochemical marker for differentiating T1DM and T2DM among young Asian Indians.

Effects of individual and combined dietary weight loss and exercise interventions in postmenopausal women on adiponectin and leptin levels.

PubMed

Abbenhardt, C; McTiernan, A; Alfano, C M; Wener, M H; Campbell, K L; Duggan, C; Foster-Schubert, K E; Kong, A; Toriola, A T; Potter, J D; Mason, C; Xiao, L; Blackburn, G L; Bain, C; Ulrich, C M

2013-08-01

Excess body weight and a sedentary lifestyle are associated with the development of several diseases, including cardiovascular disease, diabetes and cancer in women. One proposed mechanism linking obesity to chronic diseases is an alteration in adipose-derived adiponectin and leptin levels. We investigated the effects of 12-month reduced calorie, weight loss and exercise interventions on adiponectin and leptin concentrations. Overweight/obese postmenopausal women (n = 439) were randomized as follows: (i) a reduced calorie, weight-loss diet (diet; N = 118), (ii) moderate-to-vigorous intensity aerobic exercise (exercise; N = 117), (iii) a combination of a reduced calorie, weight-loss diet and moderate-to-vigorous intensity aerobic exercise (diet + exercise; N = 117), and (iv) control (N = 87). The reduced calorie diet had a 10% weight-loss goal. The exercise intervention consisted of 45 min of moderate-to-vigorous aerobic activity 5 days per week. Adiponectin and leptin levels were measured at baseline and after 12 months of intervention using a radioimmunoassay. Adiponectin increased by 9.5% in the diet group and 6.6% in the diet + exercise group (both P ≤ 0.0001 vs. control). Compared with controls, leptin decreased with all interventions (diet + exercise, -40.1%, P < 0.0001; diet, -27.1%, P < 0.0001; exercise, -12.7%, P = 0.005). The results were not influenced by the baseline body mass index (BMI). The degree of weight loss was inversely associated with concentrations of adiponectin (diet, P-trend = 0.0002; diet + exercise, P-trend = 0.0005) and directly associated with leptin (diet, P-trend < 0.0001; diet + exercise, P-trend < 0.0001). Weight loss through diet or diet + exercise increased adiponectin concentrations. Leptin concentrations decreased in all of the intervention groups, but the greatest reduction occurred with diet + exercise. Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin. © 2013 The Association for the Publication of the Journal of Internal Medicine.

Adiponectin, Leptin, IGF-1, and Tumor Necrosis Factor Alpha As Potential Serum Biomarkers for Non-Invasive Diagnosis of Colorectal Adenoma in African Americans.

PubMed

Ashktorab, Hassan; Soleimani, Akbar; Nichols, Alexandra; Sodhi, Komal; Laiyemo, Adeyinka O; Nunlee-Bland, Gail; Nouraie, Seyed Mehdi; Brim, Hassan

2018-01-01

The potential role of adiponectin, leptin, IGF-1, and tumor necrosis factor alpha (TNF-α) as biomarkers in colorectal adenoma is not clear. Therefore, we aimed to investigate the blood serum levels of these biomarkers in colorectal adenoma. The case-control study consisted of serum from 180 African American patients with colon adenoma (cases) and 198 healthy African Americans (controls) at Howard University Hospital. We used ELISA for adiponectin, leptin, IGF-1, and TNF-α detection and quantification. Statistical analysis was performed by t -test and multivariate logistic regression. The respective differences in median leptin, adiponectin, IGF-1, and TNF-α levels between control and case groups (13.9 vs. 16.4), (11.3 vs. 46.0), (4.5 vs. 12.9), and (71.4 vs. 130.8) were statistically significant ( P  < 0.05). In a multivariate model, the odds ratio for adiponectin, TNF-α, and IGF-1 were 2.0 (95% CI = 1.6-2.5; P  < 0.001), 1.5 (95% CI = 1.5(1.1-2.0); P  = 0.004), and 1.6 (95% CI = 1.3-2.0; P  < 0.001), respectively. There was a positive correlation between serum adiponectin and IGF-1 concentrations with age ( r  = 0.17, P  < 0.001 and r  = 0.13, P  = 0.009), TNF-α, IGF-1, and leptin concentration with body mass index (BMI) ( r  = 0.44, P  < 0.001; r  = 0.11, P  = 0.03; and r  = 0.48, P  < 0.001), respectively. Also, there was a negative correlation between adiponectin and leptin concentrations with BMI ( r  = -0.40, P  < 0.001), respectively. These data support the hypothesis that adiponectin, IGF-1, and TNF-α high levels correlate with higher risk of colon adenoma and can thus be used for colorectal adenomas risk assessment.

Reference values for leptin and adiponectin in children below the age of 10 based on the IDEFICS cohort.

PubMed

Erhardt, E; Foraita, R; Pigeot, I; Barba, G; Veidebaum, T; Tornaritis, M; Michels, N; Eiben, G; Ahrens, W; Moreno, L A; Kovács, E; Molnár, D

2014-09-01

To establish age- and sex-specific reference values for serum leptin and adiponectin in normal-weight 3.0-8.9-year old European children. Blood samples for hormone analysis were taken from 1338 children of the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health Effects in Children and infantS) study cohort. Only normal-weight children aged 3.0-8.9 years were included (n=539) in our analysis. Using the General Additive Model for Location Scale and Shape, age- and sex-specific percentiles were derived. The influence of under/overweight and obesity on the proposed reference curves based on normal-weight children was investigated in several sensitivity analyses using the sample without obese children (n=1015) and the whole study sample (n=1338). There was a negative age trend of adiponectin blood levels and a positive trend of leptin levels in boys and girls. Percentiles derived for girls were generally higher than those obtained for boys. The corresponding age-specific differences of the 97th percentile ranged from -2.2 to 4.6 μg ml(-1) and from 2.2 to 4.8 ng ml(-1) for adiponectin and leptin, respectively. According to our knowledge, these are the first reference values of leptin and adiponectin in prepubertal, normal-weight children. The presented adiponectin and leptin reference curves may allow for a more differentiated interpretation of children's hormone levels in epidemiological and clinical studies.

Serum level of orexin-A, leptin, adiponectin and insulin in north Indian obese women.

PubMed

Mishra, Sameeksha; Gupta, Vani; Mishra, Supriya; Sachan, Rekha; Asthana, Akash

2017-12-01

Obesity is regulated by different metabolic factors like leptin, adiponectin insulin and neuropeptide orexin-A. The aim of this study is to assess the role of these hormones and their interrelationship with obesity in north Indian women. A total of 168 obese women with Body Mass Index (BMI)>30kg/m 2 and 150 lean women (BMI<25kg/m 2 ) as control were recruited in this study. Women with obesity were further subdivided into two groups according to their BMI, 71 overweight women with the BMI 25-29.9kg/m 2 (mean±S.D: 27.87±0.71) and the 97 obese women with BMI>30kg/m 2 (34.68±1.90). Orexin -A, leptin and adiponectin were estimated using quantitative sandwich enzyme linked immunoassay and insulin was estimated by using an immuno-radiometric assay. Orexin -A and adiponectin level were significantly lower however, leptin and inulin level were significantly higher in obese women as compared with control group. Further, the one- way group analysis showed that the orexin -A and adiponectin level were significantly lower but leptin and insulin level was significantly higher in obese women as compared to overweight and control group respectively. Result showed that the level of adiponectin, leptin, orexin-A and insulin play an important role in the regulation of energy expenditure. In obesity, the activity of these peptides is disturbed. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Expression of adipokines in osteoarthritis osteophytes and their effect on osteoblasts.

PubMed

Junker, Susann; Frommer, Klaus W; Krumbholz, Grit; Tsiklauri, Lali; Gerstberger, Rüdiger; Rehart, Stefan; Steinmeyer, Jürgen; Rickert, Markus; Wenisch, Sabine; Schett, Georg; Müller-Ladner, Ulf; Neumann, Elena

2017-10-01

Osteophyte formation in osteoarthritis (OA) is mediated by increased osteoblast activity, which is -in turn- regulated by the Wnt signaling pathway. Obesity is regarded a risk factor in OA, yet little is known about the interaction between adipose tissue-derived factors, the adipokines, and bone formation, although adipokines are associated with the pathogenesis of OA. Therefore, the effect of adipokines on bone and cartilage forming cells and osteophyte development was analyzed. Human OA osteophytes were histologically characterized and adipokine expression was evaluated by immunohistochemistry. Osteoblasts and chondrocytes were isolated from OA tissue and stimulated with adiponectin, resistin, or visfatin. Cytokine and osteoblast/chondrocyte markers were quantified and activation of Wnt and p38 MAPK signaling was analyzed. Adiponectin, resistin, and visfatin were expressed in OA osteophytes by various articular cell types. Stimulation of OA osteoblasts with adiponectin and of OA chondrocytes with visfatin led to an increased release of proinflammatory mediators but not to osteoblast differentiation or activation. Additionally, visfatin increased matrix degrading factors in chondrocytes. Wnt signaling was not altered by adipokines, but adiponectin induced p38 MAPK signaling in osteoblasts. Adipokines are present in OA osteophytes, and adiponectin and visfatin increase the release of proinflammatory mediators by osteoblasts and chondrocytes. The effects of adiponectin were mediated by p38 MAPK but not Wnt signaling in osteoblasts. Therefore, the results support the idea that adipokines do not directly influence osteophyte development but the proinflammatory conditions in OA. Copyright © 2016 Elsevier B.V. All rights reserved.

Adiponectin and Its Receptors in the Ovary: Further Evidence for a Link between Obesity and Hyperandrogenism in Polycystic Ovary Syndrome

PubMed Central

Comim, Fabio V.; Hardy, Kate; Franks, Stephen

2013-01-01

Polycystic ovary syndrome (PCOS), characterized by ovarian androgen excess, is the commonest endocrine disorder in women. Obesity increases androgen synthesis, a phenomenon attributed to the accompanying hyperinsulinemia. Our hypothesis was that adipokines, fat cell-derived hormones, play a direct role in modulating ovarian androgen secretion. Therefore, the aims of this study were to explore the effects of adipokines (in particular, adiponectin) on ovarian steroidogenesis and compare the expression of adiponectin receptors in ovaries from women with and without PCO. Sections of archived human ovaries (nine from women with normal ovaries and 16 with PCOS, classified histologically, with reference to menstrual history and ultrasound) were analysed by quantitative morphometry and the proportion of positive-labelling cells compared. In addition, studies of androgen production in relation to adipokine function in primary bovine theca cell culture were also performed. A significantly lower proportion of theca cells expressed adiponectin receptors 1 and 2 (AdipoR1, AdipoR2) in polycystic ovaries than in normal ovaries. In cultured theca cells, adiponectin suppressed androstenedione production and gene expression of LH receptor and key enzymes in the androgen synthesis pathway. Moreover, knockdown of genes for AdipoR1 and AdipoR2 was associated with increased androstenedione secretion by bovine theca cells. These results provide evidence for a direct link between fat cell metabolism and ovarian steroidogenesis, suggesting that disruption of adiponectin and/or its receptors plays a key role in pathogenesis of hyperandrogenism in PCOS. PMID:24260388

Leptin and adiponectin supplementation modifies mesenteric lymph node lymphocyte composition and functionality in suckling rats.

PubMed

Grases-Pintó, Blanca; Abril-Gil, Mar; Rodríguez-Lagunas, Maria J; Castell, Margarida; Pérez-Cano, Francisco J; Franch, Àngels

2018-03-01

At birth, when immune responses are insufficient, there begins the development of the defence capability against pathogens. Leptin and adiponectin, adipokines that are present in breast milk, have been shown to play a role in the regulation of immune responses. We report here, for the first time, the influence of in vivo adipokine supplementation on the intestinal immune system in early life. Suckling Wistar rats were daily supplemented with leptin (0·7 μg/kg per d, n 36) or adiponectin (35 μg/kg per d, n 36) during the suckling period. The lymphocyte composition, proliferation and cytokine secretion from mesenteric lymph node lymphocytes (on days 14 and 21), as well as intestinal IgA and IgM concentration (day 21), were evaluated. At day 14, leptin supplementation significantly increased the TCRαβ + cell proportion in mesenteric lymph nodes, in particular owing to an increase in the TCRαβ + CD8+ cell population. Moreover, the leptin or adiponectin supplementation promoted the early development CD8+ cells, with adiponectin being the only adipokine capable of enhancing the lymphoproliferative ability at the end of the suckling period. Although leptin decreased intestinal IgA concentration, it had a trophic effect on the intestine in early life. Supplementation of both adipokines modulated the cytokine profile during (day 14) and at the end (day 21) of the suckling period. These results suggest that leptin and adiponectin during suckling play a role in the development of mucosal immunity in early life.

Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response?

PubMed Central

Khedr, Mohamed Ahmed; Sira, Ahmad Mohamed; Saber, Magdy Anwar; Raia, Gamal Yousef

2015-01-01

Background & Aims. The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p < 0.0001, p = 0.071, and p = 0.87, resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p < 0.0001) and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, p < 0.0001 and p = 0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p = 0.044). Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy. PMID:26640716

Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response?

PubMed

Khedr, Mohamed Ahmed; Sira, Ahmad Mohamed; Saber, Magdy Anwar; Raia, Gamal Yousef

2015-01-01

Background & Aims. The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p < 0.0001, p = 0.071, and p = 0.87, resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p < 0.0001) and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, p < 0.0001 and p = 0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p = 0.044). Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy.

Adipokines in human milk and risk of overweight in early childhood: a prospective cohort study.

PubMed

Weyermann, Maria; Brenner, Hermann; Rothenbacher, Dietrich

2007-11-01

Multiple studies have suggested that breast-feeding can prevent obesity, but the evidence remains inconclusive. The concentrations of specific constituents of human milk, such as adipokines, may play a role in this relationship, and these have rarely been considered. We assessed the role of adiponectin and leptin in human milk in childhood overweight. Between November 2000 and November 2001 all women delivering at the Department of Gynecology and Obstetrics at the University of Ulm, Germany were invited to participate in the study together with their healthy newborns. Milk samples were collected 6 weeks postpartum. Adiponectin and leptin levels were determined by commercially available ELISA. Active follow-up was performed at age 12 and 24 months. Of the 674 breast-fed children, 56 (8%) were overweight at the age of 2 years. Median adiponectin and leptin levels in milk were 10.9 ng/mL and 174.5 pg/mL, respectively. Adjusted odds ratio for overweight at the age of 2 was 1.6 (95% confidence interval = 1.0-2.6) per unit increase of log adiponectin and 1.1 (0.8-1.5) per unit increase of log leptin. Among children who were breast-fed for at least 6 months, adjusted odds ratios were 2.1 (1.1-4.2) per unit increase of log adiponectin, and 1.1 (0.7-1.6) per unit increase of log leptin. High levels of adiponectin in maternal milk may be a risk factor for childhood overweight.

Differential metabolic effects of constant moderate versus high intensity interval training in high-fat fed mice: possible role of muscle adiponectin.

PubMed

Martinez-Huenchullan, Sergio F; Maharjan, Babu Raja; Williams, Paul F; Tam, Charmaine S; Mclennan, Susan V; Twigg, Stephen M

2018-02-01

Exercise regimens may have differing effects in the presence of obesity. In addition to being fat derived, adiponectin has recently been described as a myokine that regulates insulin sensitivity, which may link to exercise-related metabolic benefits in obesity. Whether skeletal muscle adiponectin varies in different exercise modalities is unclear. This study investigated the comparative effects of 10 weeks of endurance constant-moderate intensity exercise (END) with high intensity interval training (HIIT), on metabolic outcomes, including muscle adiponectin in a mouse model of diet-induced obesity. Ten-week-old male C57BL/6 mice were fed a high-fat diet (HFD) (45% FAT) or standard CHOW diet ab libitum and underwent one of three training regimes: (1) no exercise, (2) END, or (3) HIIT (8 bouts of 2.5 min with eight periods of rest of 2.5 min) for 10 weeks (3 × 40 min sessions/week). Chow-fed mice acted as controls. Compared with HFD alone, both training programs similarly protected against body weight gain (HFD = 45 ± 2; END = 37 ± 2; HIIT = 36 ± 2 g), preserved lean/fat tissue mass ratio (HFD = 0.64 ± 0.09; END = 0.34 ± 0.13; HIIT = 0.33 ± 0.13), and improved blood glucose excursion during an insulin tolerance test (HFD = 411 ± 54; END = 350 ± 57; HIIT = 320 ± 66 arbitrary units [AU]). Alterations in fasting glycemia, insulinemia, and AST/ALT ratios were prevented only by END. END, but not HIIT increased skeletal muscle adiponectin mRNA (14-fold; P < 0.05) and increased protein content of high molecular weight (HMW) adiponectin (3.3-fold), whereas HIIT induced a milder increase (2.4-fold). Compared with HFD, neither END nor HIIT altered circulating low (LMW) or high (HMW) molecular weight adiponectin forms. Furthermore, only END prevented the HFD downregulation of PGC1α (P < 0.05) mRNA levels downstream of muscle adiponectin. These data show that different training programs affect muscle adiponectin to differing degrees. Together these results suggest that END is a more effective regimen to prevent HFD-induced metabolic disturbances in mice. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Circulating Endothelial Microparticles and Correlation of Serum 1,25-Dihydroxyvitamin D with Adiponectin, Nonesterified Fatty Acids, and Glycerol from Middle-Aged Men in China.

PubMed

Wan, Zhongxiao; Yu, Lugang; Cheng, Jinbo; Zhang, Zengli; Xu, Baohui; Pang, Xing; Zhou, Hui; Lei, Ting

2016-01-01

The aim of the present study is (1) to determine the correlation between circulating 1,25-dihydroxyvitamin D [25(OH)D] and adiponectin, nonesterified fatty acids (NEFAs), and glycerol and (2) to determine the alterations in circulating endothelial microparticles (EMPs) in Chinese male subjects with increased body mass index (BMI). A total of 45 male adults were enrolled with varied BMI [i.e., lean, overweight (OW), and obese (OB), N = 15 per group]. Blood samples were collected under overnight fasting condition, and plasma was isolated for the measurement of endothelial microparticles (EMPs), total and high-molecular weight (HMW) adiponectin, 25(OH)D, nonesterified fatty acids (NEFAs), and glycerol. Circulating 25(OH)D levels were inversely associated with total adiponectin, NEFA, and glycerol levels. There is no difference for CD62E+ or CD31+/CD42b- EMPs among 3 groups. In Chinese male adults with varied BMI, an inverse correlation existed between 25(OH)D levels and total adiponectin, NEFA, and glycerol levels; and there is no significant difference for CD62E+ or CD31+/CD42b- EMPs among lean, overweight, and obese subjects.

Circulating Endothelial Microparticles and Correlation of Serum 1,25-Dihydroxyvitamin D with Adiponectin, Nonesterified Fatty Acids, and Glycerol from Middle-Aged Men in China

PubMed Central

Wan, Zhongxiao; Yu, Lugang; Cheng, Jinbo; Zhang, Zengli; Xu, Baohui; Pang, Xing; Zhou, Hui; Lei, Ting

2016-01-01

The aim of the present study is (1) to determine the correlation between circulating 1,25-dihydroxyvitamin D [25(OH)D] and adiponectin, nonesterified fatty acids (NEFAs), and glycerol and (2) to determine the alterations in circulating endothelial microparticles (EMPs) in Chinese male subjects with increased body mass index (BMI). A total of 45 male adults were enrolled with varied BMI [i.e., lean, overweight (OW), and obese (OB), N = 15 per group]. Blood samples were collected under overnight fasting condition, and plasma was isolated for the measurement of endothelial microparticles (EMPs), total and high-molecular weight (HMW) adiponectin, 25(OH)D, nonesterified fatty acids (NEFAs), and glycerol. Circulating 25(OH)D levels were inversely associated with total adiponectin, NEFA, and glycerol levels. There is no difference for CD62E+ or CD31+/CD42b− EMPs among 3 groups. In Chinese male adults with varied BMI, an inverse correlation existed between 25(OH)D levels and total adiponectin, NEFA, and glycerol levels; and there is no significant difference for CD62E+ or CD31+/CD42b− EMPs among lean, overweight, and obese subjects. PMID:27314039

Disturbed secretion of mutant adiponectin associated with the metabolic syndrome.

PubMed

Kishida, Ken; Nagaretani, Hiroyuki; Kondo, Hidehiko; Kobayashi, Hideki; Tanaka, Sachiyo; Maeda, Norikazu; Nagasawa, Azumi; Hibuse, Toshiyuki; Ohashi, Koji; Kumada, Masahiro; Nishizawa, Hitoshi; Okamoto, Yoshihisa; Ouchi, Noriyuki; Maeda, Kazuhisa; Kihara, Shinji; Funahashi, Tohru; Matsuzawa, Yuji

2003-06-20

Adiponectin, an adipocyte-derived protein, consists of collagen-like fibrous and complement C1q-like globular domains, and circulates in human plasma in a multimeric form. The protein exhibits anti-diabetic and anti-atherogenic activities. However, adiponectin plasma concentrations are low in obese subjects, and hypoadiponectinemia is associated with the metabolic syndrome, which is a cluster of insulin resistance, type 2 diabetes mellitus, hypertension, and dyslipidemia. We have recently reported a missense mutation in the adiponectin gene, in which isoleucine at position 164 in the globular domain is substituted with threonine (I164T). Subjects with this mutation showed markedly low level of plasma adiponectin and clinical features of the metabolic syndrome. Here, we examined the molecular characteristics of the mutant protein associated with a genetic cause of hypoadiponectinemia. The current study revealed (1) the mutant protein showed an oligomerization state similar to the wild-type as determined by gel filtration chromatography and, (2) the mutant protein exhibited normal insulin-sensitizing activity, but (3) pulse-chase study showed abnormal secretion of the mutant protein from adipose tissues. Our results suggest that I164T mutation is associated with hypoadiponectinemia through disturbed secretion into plasma, which may contribute to the development of the metabolic syndrome.

APPL1 Mediates Adiponectin-Induced LKB1 Cytosolic Localization Through the PP2A-PKCζ Signaling Pathway

PubMed Central

Deepa, Sathyaseelan S.; Zhou, Lijun; Ryu, Jiyoon; Wang, Changhua; Mao, Xuming; Li, Cai; Zhang, Ning; Musi, Nicolas; DeFronzo, Ralph A.; Liu, Feng

2011-01-01

We recently found that the adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif (APPL)1 is essential for mediating adiponectin signal to induce liver kinase B (LKB)1 cytosloic translocation, an essential step for activation of AMP-activated protein kinase (AMPK) in cells. However, the underlying molecular mechanisms remain unknown. Here, we demonstrate that treating C2C12 myotubes with adiponectin promoted APPL1 interaction with protein phosphatase 2A (PP2A) and protein kinase Cζ (PKCζ), leading to the activation of PP2A and subsequent dephosphorylation and inactivation of PKCζ. The adiponectin-induced inactivation of PKCζ results in dephosphorylation of LKB1 at Ser307 and its subsequent translocation to the cytosol, where it stimulates AMPK activity. Interestingly, we found that metformin also induces LKB1 cytosolic translocation, but the stimulation is independent of APPL1 and the PP2A-PKCζ pathway. Together, our study uncovers a new mechanism underlying adiponectin-stimulated AMPK activation in muscle cells and shed light on potential targets for prevention and treatment of insulin resistance and its associated diseases. PMID:21835890

Globular Adiponectin Inhibits Lipopolysaccharide-Primed Inflammasomes Activation in Macrophages via Autophagy Induction: The Critical Role of AMPK Signaling

PubMed Central

Kim, Mi Jin; Kim, Eun Hye; TiliJa Pun, Nirmala; Chang, Jae-Hoon; Kim, Jung-Ae; Jeong, Jee-Heon; Choi, Dong Young; Kim, Sang-Hyun; Park, Pil-Hoon

2017-01-01

The inflammasome acts as a key platform for the activation of pro-inflammatory cytokines. Adiponectin exhibits potent anti-inflammatory properties. However, the effect of adiponectin on the modulation of the inflammasome has not been explored. Herein, we show that globular adiponectin (gAcrp) suppressed lipopolysaccharide (LPS)-primed inflammasomes activation in murine peritoneal macrophages judged by prevention of interleukin-1β (IL-1β) maturation, caspase-1 activation, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) speck formation, and pyroptotic cell death. Interestingly, pretreatment with 3-methyl adenine, a pharmacological inhibitor of autophagy, abrogated the suppressive effects of gAcrp on IL-1β secretion and caspase-1 activation, indicating the crucial role of autophagy induction in gAcrp-modulation of the inflammasome activation. In addition, inhibition of 5′Adenosine monophaspahate (AMP)-activated protein kinase (AMPK) signaling abolished suppressive effect of gAcrp on inflammasomes activation. Furthermore, autophagy induction or inhibition of the inflammasome activation by gAcrp was not observed in macrophages deficient in AMPK. Taken together, these results indicate that adiponectin inhibits LPS-primed inflammasomes activation in macrophages via autophagy induction and AMPK signaling-dependent mechanisms. PMID:28617316

Does Dietary Iodine Regulate Oxidative Stress and Adiponectin Levels in Human Breast Milk?

PubMed Central

Gutiérrez-Repiso, Carolina; Velasco, Inés; Garcia-Escobar, Eva; Garcia-Serrano, Sara; Rodríguez-Pacheco, Francisca; Linares, Francisca; Ruiz de Adana, Maria Soledad; Rubio-Martin, Elehazara; Garrido-Sanchez, Lourdes; Cobos-Bravo, Juan Francisco; Priego-Puga, Tatiana; Rojo-Martinez, Gemma; Soriguer, Federico

2014-01-01

Abstract Little is known about the association between iodine and human milk composition. In this study, we investigated the association between iodine and different markers of oxidative stress and obesity-related hormones in human breast milk. This work is composed of two cross-sectional studies (in lactating women and in the general population), one prospective and one in vitro. In the cross-sectional study in lactating women, the breast milk iodine correlated negatively with superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) activities, and with adiponectin levels. An in vitro culture of human adipocytes with 1 μM potassium iodide (KI, dose similar to the human breast milk iodine concentration) produced a significant decrease in adiponectin, GSH-Px, SOD1, and SOD2 mRNA expression. However, after 2 months of treatment with KI in the prospective study, a positive correlation was found between 24-h urinary iodine and serum adiponectin. Our observations lead to the hypothesis that iodine may be a factor directly involved in the regulation of oxidative stress and adiponectin levels in human breast milk. Antioxid. Redox Signal. 20, 847–853. PMID:24001137

Differential Effects of Leptin and Adiponectin in Endothelial Angiogenesis

PubMed Central

Adya, Raghu; Tan, Bee K.; Randeva, Harpal S.

2015-01-01

Obesity is a major health burden with an increased risk of cardiovascular morbidity and mortality. Endothelial dysfunction is pivotal to the development of cardiovascular disease (CVD). In relation to this, adipose tissue secreted factors termed “adipokines” have been reported to modulate endothelial dysfunction. In this review, we focus on two of the most abundant circulating adipokines, that is, leptin and adiponectin, in the development of endothelial dysfunction. Leptin has been documented to influence a multitude of organ systems, that is, central nervous system (appetite regulation, satiety factor) and cardiovascular system (endothelial dysfunction leading to atherosclerosis). Adiponectin, circulating at a much higher concentration, exists in different molecular weight forms, essentially made up of the collagenous fraction and a globular domain, the latter being investigated minimally for its involvement in proinflammatory processes including activation of NF-κβ and endothelial adhesion molecules. The opposing actions of the two forms of adiponectin in endothelial cells have been recently demonstrated. Additionally, a local and systemic change to multimeric forms of adiponectin has gained importance. Thus detailed investigations on the potential interplay between these adipokines would likely result in better understanding of the missing links connecting CVD, adipokines, and obesity. PMID:25650072

Relationship between serum adiponectin concentration, body condition score, and peripheral tissue insulin response of dairy cows during the dry period.

PubMed

De Koster, J; Urh, C; Hostens, M; Van den Broeck, W; Sauerwein, H; Opsomer, G

2017-04-01

The aim of the present study was to describe the relationship between serum adiponectin concentration and peripheral tissue insulin response in dairy cows with a variable body condition score (BCS) during the dry period. Cows were selected at the beginning of the dry period based on BCS (BCS <3.75, n = 4; BCS >3.75, n = 5). Animals were followed from the beginning of the dry period by weekly blood sampling and assessment of BCS and backfat thickness. Weekly blood samples were analyzed for adiponectin concentration using a bovine specific ELISA. Hyperinsulinemic euglycemic clamp tests were performed at the end of the dry period to measure peripheral tissue insulin response. Insulin dose response curves were established for both glucose and fatty acid metabolism. Regression analysis revealed that the serum concentrations of adiponectin dropped at the end of the dry period (P < 0.05) and were negatively associated with BCS (P < 0.05). At the level of the glucose metabolism, serum concentrations of adiponectin were positively correlated with insulin responsiveness (reflecting the maximal effect of insulin; r = 0.76, P < 0.05), but not with insulin sensitivity (reflecting the insulin concentration needed to achieve halfmaximal effect; r = -0.54, P = 0.13). At the level of the fatty acid metabolism, greater adiponectin concentrations were negatively correlated with lower NEFA levels during the HEC test reflecting the insulin responsiveness of the NEFA metabolism (r = -0.61, P = 0.08), whereas there was no association with the insulin sensitivity of the NEFA metabolism (r = -0.16, P = 0.67). In conclusion, serum concentrations of adiponectin were negatively associated with the BCS of dairy cows during the dry period and positively associated with insulin responsiveness of the glucose and fatty acid metabolism. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of ADIPOQ +45T>G polymorphism with body fat mass and blood levels of soluble adiponectin and inflammation markers in a Mexican-Mestizo population

PubMed Central

Guzman-Ornelas, Milton-Omar; Chavarria-Avila, Efrain; Munoz-Valle, Jose-Francisco; Armas-Ramos, Laura-Elizabeth; Castro-Albarran, Jorge; Aldrete, Maria Elena Aguilar; Oregon-Romero, Edith; Mercado, Monica Vazquez-Del; Navarro-Hernandez, Rosa-Elena

2012-01-01

Purpose Obesity is a disease with genetic susceptibility characterized by an increase in storage and irregular distribution of body fat. In obese patients, the decrease in the Adiponectin gene (ADIPOQ) expression has been associated with a systemic low-grade inflammatory state. Our aim was to investigate the relationship between ADIPOQ +45T>G gene simple nucleotide polymorphism (SNP rs2241766) with serum adiponectin (sAdiponectin), distribution of body fat storage, and inflammation markers. Subjects and methods In this cross-sectional study, 242 individuals from Western Mexico characterized as Mexican-Mestizo and classified by body mass index (BMI), were included. Anthropometrics, body composition, body fat distribution, and inflammation markers were measured by routine methods. Genotypes were characterized using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and sAdiponectin by the ELISA method. A P-value <0.05 was considered the statistically significant threshold. Results sAdiponectin is associated with BMI (P < 0.001) and the genotypes (P < 0.001 to 0.0046) GG (8169 ± 1162 ng/mL), TG (5189 ± 501 ng/mL), and TT (3741 ± 323 ng/mL), but the SNP ADIPOQ +45T>G is not associated with BMI. However, the detailed analysis showed association of this SNP with a pattern of fat distribution and correlations (P < 0.05) with inflammation markers and distribution of body fat storage (Pearson’s r = −0.169 to −0.465) were found. Conclusion In this study, we have suggested that the ADIPOQ +45G allele could be associated with distribution of body fat storage in obesity. On the other hand, as no association was observed between ADIPOQ +45T>G gene polymorphism and obesity, it cannot be concluded that the ADIPOQ +45G allele is responsible for the increase of adiponectin levels. PMID:23118546

The associations between the growth hormone/insulin-like growth factor-1 axis, adiponectin, resistin and metabolic profile in children with growth hormone deficiency before and during growth hormone treatment.

PubMed

Witkowska-Sędek, Ewelina; Rumińska, Małgorzata; Stelmaszczyk-Emmel, Anna; Majcher, Anna; Pyrżak, Beata

2018-01-01

This study investigated associations between the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis, adiponectin, resistin and metabolic profile in 47 GH-deficient children before and during 12 months of GH treatment. 23 short age-matched children without growth hormone deficiency (GHD) or any genetic or chronic disorders were recruited as controls at baseline. Metabolic evaluation included measurements of adiponectin, resistin, IGF-1, total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, insulin, glycated haemoglobin (HbA1c), thyroid stimulating hormone (TSH) and free thyroxine (free T4) concentrations. The GH-deficient children had significantly higher adiponectin (p<0.05) and total cholesterol (p<0.05) levels, and a significantly lower level of resistin (p<0.05) than the controls. Resistin at 6 months of GH treatment significantly correlated with changes in height SDS in that period (r=0.35) and with the level of fasting insulin (r=0.50), the HOMA-IR (r=0.56) and the QUICKI (r=-0.53) at 12 months of therapy. Adiponectin level at 12 months of GH treatment was significantly associated with changes in HDL-C within the first 6 (r=0.73) and within 12 (r=0.56) months of therapy, while resistin significantly correlated with an increment in IGF-1 within 12 months of treatment (r=0.49) and with total-C at 12 months (r=0.56). Untreated GH-deficient children had higher adiponectin and lower resistin levels than healthy short children without GHD. Adiponectin and resistin levels did not change significantly during the first 12 months of GH therapy. Good responders to GH treatment had a tendency for higher resistin level during GH therapy, which positively correlates with the insulin resistance parameters.

Circulating leptin and adiponectin are associated with insulin resistance in healthy postmenopausal women with hot flashes.

PubMed

Huang, Wan-Yu; Chang, Chia-Chu; Chen, Dar-Ren; Kor, Chew-Teng; Chen, Ting-Yu; Wu, Hung-Ming

2017-01-01

Hot flashes have been postulated to be linked to the development of metabolic disorders. This study aimed to evaluate the relationship between hot flashes, adipocyte-derived hormones, and insulin resistance in healthy, non-obese postmenopausal women. In this cross-sectional study, a total of 151 women aged 45-60 years were stratified into one of three groups according to hot-flash status over the past three months: never experienced hot flashes (Group N), mild-to-moderate hot flashes (Group M), and severe hot flashes (Group S). Variables measured in this study included clinical parameters, hot flash experience, fasting levels of circulating glucose, lipid profiles, plasma insulin, and adipocyte-derived hormones. Multiple linear regression analysis was used to evaluate the associations of hot flashes with adipocyte-derived hormones, and with insulin resistance. The study was performed in a hospital medical center. The mean (standard deviation) of body-mass index was 22.8(2.7) for Group N, 22.6(2.6) for Group M, and 23.5(2.4) for Group S, respectively. Women in Group S displayed statistically significantly higher levels of leptin, fasting glucose, and insulin, and lower levels of adiponectin than those in Groups M and N. Multivariate linear regression analysis revealed that hot-flash severity was significantly associated with higher leptin levels, lower adiponectin levels, and higher leptin-to-adiponectin ratio. Univariate linear regression analysis revealed that hot-flash severity was strongly associated with a higher HOMA-IR index (% difference, 58.03%; 95% confidence interval, 31.00-90.64; p < 0.001). The association between hot flashes and HOMA-IR index was attenuated after adjusting for leptin or adiponectin and was no longer significant after simultaneously adjusting for leptin and adiponectin. The present study provides evidence that hot flashes are associated with insulin resistance in postmenopausal women. It further suggests that hot flash association with insulin resistance is dependent on the combination of leptin and adiponectin variables.

Adipocytokine and ghrelin responses to acute exercise and sport training in children during growth and maturation.

PubMed

Jürimäe, Jaak

2014-11-01

Physical exercise is known to regulate energy balance. Important to this regulatory system is the existence of several peptides that communicate the status of body energy stores to the brain and are related to the body fatness including leptin, adiponectin and ghrelin. These hormones assist in regulating energy balance as well as somatic and pubertal growth in children. It appears that rather few studies have investigated the responses of leptin, adiponectin and ghrelin to acute exercise and these studies have demonstrated no changes in these peptides as a result of exercise. Leptin levels are decreased and may remain unchanged advancing from prepuberty to pubertal maturation in young male and female athletes. A limited number of studies indicate that adiponectin levels are not different between prepubertal and pubertal athletes and untrained controls. However, in certain circumstances circulating adiponectin could be increased in young athletes after onset of puberty as a result of heavily increased energy expenditure. Ghrelin levels are elevated in young sportsmen. However, pubertal onset decreases ghrelin levels in boys and girls even in the presence of chronically elevated energy expenditure as seen in young athletes. Ghrelin may also be used as an indicator of energy imbalance across the menstrual cycle in adolescent athletes. There are no studies with high-molecular-weight adiponectin and only very few studies with acylated ghrelin responses to acute exercise and chronic training have been performed in young athletes. Since these forms of adiponectin and ghrelin have been thought to be bioactive forms, further studies with these specific forms of adiponectin and ghrelin are needed. In conclusion, further studies should be conducted to investigate the response of these hormones to acute and chronic negative energy balance to better understand their role in regulating energy balance during growth and maturation in young athletes.

Association of ADIPOQ +45T>G polymorphism with body fat mass and blood levels of soluble adiponectin and inflammation markers in a Mexican-Mestizo population.

PubMed

Guzman-Ornelas, Milton-Omar; Chavarria-Avila, Efrain; Munoz-Valle, Jose-Francisco; Armas-Ramos, Laura-Elizabeth; Castro-Albarran, Jorge; Aguilar Aldrete, Maria Elena; Oregon-Romero, Edith; Vazquez-Del Mercado, Monica; Navarro-Hernandez, Rosa-Elena

2012-01-01

Obesity is a disease with genetic susceptibility characterized by an increase in storage and irregular distribution of body fat. In obese patients, the decrease in the Adiponectin gene (ADIPOQ) expression has been associated with a systemic low-grade inflammatory state. Our aim was to investigate the relationship between ADIPOQ +45T>G gene simple nucleotide polymorphism (SNP rs2241766) with serum adiponectin (sAdiponectin), distribution of body fat storage, and inflammation markers. In this cross-sectional study, 242 individuals from Western Mexico characterized as Mexican-Mestizo and classified by body mass index (BMI), were included. Anthropometrics, body composition, body fat distribution, and inflammation markers were measured by routine methods. Genotypes were characterized using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and sAdiponectin by the ELISA method. A P-value <0.05 was considered the statistically significant threshold. sAdiponectin is associated with BMI (P < 0.001) and the genotypes (P < 0.001 to 0.0046) GG (8169 ± 1162 ng/mL), TG (5189 ± 501 ng/mL), and TT (3741 ± 323 ng/mL), but the SNP ADIPOQ +45T>G is not associated with BMI. However, the detailed analysis showed association of this SNP with a pattern of fat distribution and correlations (P < 0.05) with inflammation markers and distribution of body fat storage (Pearson's r = -0.169 to -0.465) were found. In this study, we have suggested that the ADIPOQ +45G allele could be associated with distribution of body fat storage in obesity. On the other hand, as no association was observed between ADIPOQ +45T>G gene polymorphism and obesity, it cannot be concluded that the ADIPOQ +45G allele is responsible for the increase of adiponectin levels.

A low-fat high-carbohydrate diet reduces plasma total adiponectin concentrations compared to a moderate-fat diet with no impact on biomarkers of systemic inflammation in a randomized controlled feeding study.

PubMed

Song, Xiaoling; Kestin, Mark; Schwarz, Yvonne; Yang, Pamela; Hu, Xiaojun; Lampe, Johanna W; Kratz, Mario

2016-02-01

We compared the effects of a eucaloric moderate-fat diet (18% protein, 36% fat, and 46% carbohydrate), a eucaloric low-fat high-carbohydrate diet (18% protein, 18% fat, and 64% carbohydrate), and a low-calorie (33% reduced) low-fat high-carbohydrate diet on biomarkers of systemic inflammation. We randomly assigned 102 participants (age 21-76 years and BMI 19.2-35.5 kg/m(2)) to the three different diets for 6 weeks in a parallel design intervention trial. All foods were provided. Ninety-three participants completed all study procedures; 92 were included in the analyses. Endpoints included plasma C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis factor receptors I and II (sTNFRI and II), and adiponectin. In the unadjusted primary analyses, none of the endpoints were differentially affected by the dietary interventions despite the significantly greater reductions in body weight and fat mass in participants consuming the low-calorie low-fat diet compared to the eucaloric diets (p < 0.001). When including weight change in the model in secondary analysis, adiponectin tended to be increased with weight loss (time × weight change interaction, p = 0.051). Adjusted for weight change, adiponectin was reduced in the groups consuming the low-fat diets relative to the moderate-fat diet (p = 0.008). No effect of the intervention diets or weight loss on CRP, IL-6, or sTNFRI and II was seen in these secondary analyses. In relatively healthy adults, moderate weight loss had minimal effects on systemic inflammation, and raised plasma adiponectin only modestly. A lower dietary fat and higher carbohydrate content had little impact on measures of systemic inflammation, but reduced adiponectin concentrations compared to a moderate-fat diet. The latter may be of concern given the consistent and strong inverse association of plasma adiponectin with many chronic diseases.

Low circulating total adiponectin, especially its non-high-molecular weight fraction, represents a promising risk factor for colorectal cancer: a meta-analysis.

PubMed

Lu, Weiqun; Huang, Zhiliang; Li, Nan; Liu, Haiying

2018-01-01

The principal goal of this meta-analysis is to test the hypothesis that circulating total adiponectin or certain fractions may represent a promising biological candidate in modulating the risk of colorectal cancer. The processes of paper identification, paper selection and data extraction were accomplished independently by two authors. Effect-size estimates were expressed as weighted mean difference (WMD) and 95% confidence interval (95% CI). A total of 31 papers including 48 qualified studies (7,554 patients with colorectal cancer and 9,798 controls) were meta-analyzed. Pooling all studies found that circulating total adiponectin was significantly lower in patients with colorectal cancer than in controls (WMD: -0.76 µg/mL, 95% CI: -1.20 to -0.32, p =0.001), with significant heterogeneity ( I 2 : 94.2%) and low publication bias (Egger's p =0.336). By adiponectin fractions, the difference in high-molecular weight (HMW) adiponectin was comparable between the two groups (WMD: -0.22 µg/mL, 95% CI: -0.70 to 0.25, p =0.350), while non-HMW adiponectin was significantly lower in patients with colorectal cancer than in controls (WMD: -0.27 µg/mL, 95% CI: -0.35 to -0.19, p <0.001), with marginal heterogeneity ( I 2 : 52.3%). Subgroup analysis revealed that effect-size estimates were heterogeneous when grouping studies by cancer subtype, region, study design, matching status, gender and obesity. Further meta-regression analysis indicated that age and gender were significant potential sources of heterogeneity. The results showed the studied subgroups were not subject to publication bias (Egger's p <0.1). Our data collectively indicate that low circulating total adiponectin, especially its non-HMW fraction, represents a promising risk factor for colorectal cancer. Further studies are needed to explore underlying mechanisms.

CPT1A methylation is associated with plasma adiponectin.

PubMed

Aslibekyan, S; Do, A N; Xu, H; Li, S; Irvin, M R; Zhi, D; Tiwari, H K; Absher, D M; Shuldiner, A R; Zhang, T; Chen, W; Tanner, K; Hong, C; Mitchell, B D; Berenson, G; Arnett, D K

2017-03-01

Adiponectin, an adipose-secreted protein that has been linked to insulin sensitivity, plasma lipids, and inflammatory patterns, is an established biomarker for metabolic health. Despite clinical relevance and high heritability, the determinants of plasma adiponectin levels remain poorly understood. We conducted the first epigenome-wide cross-sectional study of adiponectin levels using methylation data on 368,051 cytosine-phosphate-guanine (CpG) sites in CD4+ T-cells from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n = 991). We fit linear mixed models, adjusting for age, sex, study site, T-cell purity, and family. We have identified a positive association (regression coefficient ± SE = 0.01 ± 0.001, P = 3.4 × 10 -13 ) between plasma adiponectin levels and methylation of a CpG site in CPT1A, a key player in fatty acid metabolism. The association was replicated (n = 474, P = 0.0009) in whole blood samples from the Amish participants of the Heredity and Phenotype Intervention (HAPI) Heart Study as well as White (n = 592, P = 0.0005) but not Black (n = 243, P = 0.18) participants of the Bogalusa Heart Study (BHS). The association remained significant upon adjusting for BMI and smoking in GOLDN and HAPI but not BHS. We also identified associations between methylation loci in RNF145 and UFM1 and plasma adiponectin in GOLDN and White BHS participants, although the association was not robust to adjustment for BMI or smoking. We have identified and replicated associations between several biologically plausible loci and plasma adiponectin. These findings support the importance of epigenetic processes in metabolic traits, laying the groundwork for future translational applications. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Role of Serum Adiponectin and Vitamin D in Prediabetes and Diabetes Mellitus.

PubMed

Banerjee, Anindita; Khemka, Vineet Kumar; Roy, Debashree; Poddar, Jit; Roy, Tapan Kumar Sinha; Karnam, Srikanth Arliganur

2017-06-01

The roles of deficient or deranged insulin, adiponectin and 25 hydroxy vitamin D (25[OH]D) levels regulating food intake, energy metabolism, glucose and lipid metabolism and body weight have been reported in the pathogenesis of prediabetes and type 2 diabetes mellitus. However, their congruity in the etiology of diabetes mellitus is unknown. Thus, the aim of the study was to investigate the roles of these parameters together and to establish their interrelationship in patients with prediabetes and diabetes. The preliminary cross-sectional study included 77 persons with type 2 diabetes who were matched for age, sex and body mass index (BMI); 73 persons with prediabetes; and 52 healthy control subjects. Fasting serum levels of adiponectin, insulin and 25(OH)D were measured by commercially available immune assay kits, and routine biochemical parameters were analyzed in all study groups. The results show statistically significant lower levels of serum adiponectin and serum 25(OH)D and higher serum insulin levels in persons with prediabetes or type 2 diabetes with respect to controls. The changes in the serum adiponectin or serum 25(OH)D in persons with prediabetes and type 2 diabetes were found to be inversely correlated with the serum levels of insulin. Moreover, multiple linear regression analysis, with 25(OH)D, insulin and homeostatic model assessment-insulin resistance (HOMA-IR) as the variables, revealed that serum adiponectin levels might be an independent risk factor for the progression of prediabetes and type 2 diabetes in subjects. The association of these hormones might act as a significant predictor of progression of prediabetes to type 2 diabetes. Decreased serum adiponectin levels might be an independent risk factor for progression to prediabetes and type 2 diabetes, which may help in developing experimental models of the disease or in identifying biomarkers or disease-modifying drugs. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Circulating adiponectin concentration and body composition are altered in response to high-intensity interval training.

PubMed

Shing, Cecilia M; Webb, Jessica J; Driller, Matthew W; Williams, Andrew D; Fell, James W

2013-08-01

Adiponectin influences metabolic adaptations that would prove beneficial to endurance athletes, and yet to date there is little known about the response of adiponectin concentrations to exercise, and, in particular, the response of this hormone to training in an athlete population. This study aimed to determine the response of plasma adiponectin concentrations to acute exercise after 2 different training programs and to determine the influence of the training on body composition. Seven state-level representative rowers (age: 19 ± 1.2 years [mean ± SD], height: 1.77 ± 0.10 m, body mass: 74.0 ± 10.7 kg, VO2peak 62.1 ± 7.0 ml·kg·min) participated in the double-blind, randomized crossover investigation. Rowers performed an incremental graded exercise test before and after completing 4 weeks of high-intensity interval ergometer training and 4 weeks of traditional ergometer rowing training. Rowers' body composition was assessed at baseline and after each training program. Significant increases in plasma adiponectin concentration occurred in response to maximal exercise after completion of the high-intensity interval training (p = 0.016) but not after traditional ergometer rowing training (p = 0.69). The high-intensity interval training also resulted in significant increases in mean 4-minute power output (p = 0.002) and VO2peak (p = 0.05), and a decrease in body fat percentage (p = 0.022). Mean 4-minute power output, VO2peak, and body fat percentage were not significantly different after 4 weeks of traditional ergometer rowing training (p > 0.05). Four weeks of high-intensity interval training is associated with an increase in adiponectin concentration in response to maximal exercise and a reduction in body fat percentage. The potential for changes in adiponectin concentration to reflect positive training adaptations and athlete performance level should be further explored.

Plasma Levels of Fatty Acid-Binding Protein 4, Retinol-Binding Protein 4, High-Molecular-Weight Adiponectin, and Cardiovascular Mortality Among Men With Type 2 Diabetes: A 22-Year Prospective Study.

PubMed

Liu, Gang; Ding, Ming; Chiuve, Stephanie E; Rimm, Eric B; Franks, Paul W; Meigs, James B; Hu, Frank B; Sun, Qi

2016-11-01

To examine select adipokines, including fatty acid-binding protein 4, retinol-binding protein 4, and high-molecular-weight (HMW) adiponectin in relation to cardiovascular disease (CVD) mortality among patients with type 2 diabetes mellitus. Plasma levels of fatty acid-binding protein 4, retinol-binding protein 4, and HMW adiponectin were measured in 950 men with type 2 diabetes mellitus in the Health Professionals Follow-up Study. After an average of 22 years of follow-up (1993-2015), 580 deaths occurred, of whom 220 died of CVD. After multivariate adjustment for covariates, higher levels of fatty acid-binding protein 4 were significantly associated with a higher CVD mortality: comparing extreme tertiles, the hazard ratio and 95% confidence interval of CVD mortality was 1.78 (1.22-2.59; P trend=0.001). A positive association was also observed for HMW adiponectin: the hazard ratio (95% confidence interval) was 2.07 (1.42-3.06; P trend=0.0002), comparing extreme tertiles, whereas higher retinol-binding protein 4 levels were nonsignificantly associated with a decreased CVD mortality with an hazard ratio (95% confidence interval) of 0.73 (0.50-1.07; P trend=0.09). A Mendelian randomization analysis suggested that the causal relationships of HMW adiponectin and retinol-binding protein 4 would be directionally opposite to those observed based on the biomarkers, although none of the Mendelian randomization associations achieved statistical significance. These data suggest that higher levels of fatty acid-binding protein 4 and HMW adiponectin are associated with elevated CVD mortality among men with type 2 diabetes mellitus. Biological mechanisms underlying these observations deserve elucidation, but the associations of HMW adiponectin may partially reflect altered adipose tissue functionality among patients with type 2 diabetes mellitus. © 2016 American Heart Association, Inc.

Regulation of hepatic peroxisome proliferator-activated receptor alpha expression but not adiponectin by dietary protein in finishing pigs.

PubMed

Weber, T E; Kerr, B J; Spurlock, M E

2008-10-01

Soy protein regulates adiponectin and peroxisome proliferator-activated receptor alpha (PPARalpha) in some species, but the effect of dietary soy protein on adiponectin and PPARalpha in the pig has not been studied. Therefore, the objective of this study was to determine whether soya bean meal reduction or replacement influences serum adiponectin, adiponectin mRNA, serum metabolites and the expression of PPARalpha and other genes involved in lipid deposition. Thirty-three pigs (11 pigs per treatment) were subjected to one of three dietary treatments: (i) reduced crude protein (CP) diet containing soya bean meal (RCP-Soy), (ii) high CP diet containing soya bean meal (HCP-Soy) or (iii) high CP diet with corn gluten meal replacing soya bean meal (HCP-CGM) for 35 days. Dietary treatment had no effect on overall growth performance, feed intake or measures of body composition. There was no effect of dietary treatment on serum adiponectin or leptin. Dietary treatment did not affect the abundance of the mRNAs for adiponectin, PPARalpha, PPARgamma2, lipoprotein lipase or fatty acid synthase in adipose tissue. The mRNA expression of PPARalpha, PPARgamma2, lipoprotein lipase or fatty acid synthetase in loin muscle was not affected by dietary treatment. In liver tissue, the relative abundance of PPARalpha mRNA was greater (p < 0.05) in pigs fed the HCP-Soy diets when compared to pigs fed RCP-Soy or HCP-CGM diets. Hepatic mRNA expression of acyl-CoA oxidase or fatty acid synthase was not affected by dietary treatment. Western blot analysis indicated that hepatic PPARalpha protein levels were decreased (p < 0.05) in pigs fed the RCP-Soy diets when compared to pigs fed the HCP-Soy diets. These data suggest that increasing the soy protein content of swine diets increases hepatic expression of PPARalpha without associated changes in body composition.

A low-fat high-carbohydrate diet reduces plasma total adiponectin concentrations compared to a moderate-fat diet with no impact on biomarkers of systemic inflammation in a randomized controlled feeding study

PubMed Central

Song, Xiaoling; Kestin, Mark; Schwarz, Yvonne; Yang, Pamela; Hu, Xiaojun; Lampe, Johanna W.; Kratz, Mario

2015-01-01

Purpose We compared the effects of a eucaloric moderate-fat diet (18% protein, 36% fat, 46% carbohydrate), a eucaloric low-fat high-carbohydrate diet (18% protein, 18% fat, and 64% carbohydrate), and a low-calorie (33% reduced) low-fat high-carbohydrate diet on biomarkers of systemic inflammation. Methods We randomly assigned 102 participants (age 21–76 y, BMI 19.2–35.5 kg/m2) to the three different diets for six weeks in a parallel design intervention trial. All foods were provided. Ninety-three participants completed all study procedures; 92 were included in the analyses. Endpoints included plasma C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis factor receptors I & II (sTNFRI&II), and adiponectin. Results In the unadjusted primary analyses, none of the endpoints were differentially affected by the dietary interventions despite the significantly greater reductions in body weight and fat mass in participants consuming the low-calorie low-fat diet compared to the eucaloric diets (p<0.001). When including weight change in the model in secondary analysis, adiponectin tended to be increased with weight loss (time × weight change interaction, p=0.051). Adjusted for weight change, adiponectin was reduced in the groups consuming the low-fat diets relative to the moderate-fat diet (p=0.008). No effect of the intervention diets or weight loss on CRP, IL-6 or sTNFR I & II was seen in these secondary analyses. Conclusions In relatively healthy adults, moderate weight loss had minimal effects on systemic inflammation, and raised plasma adiponectin only modestly. A lower dietary fat and higher carbohydrate content had little impact on measures of systemic inflammation, but reduced adiponectin concentrations compared to a moderate-fat diet. The latter may be of concern given the consistent and strong inverse association of plasma adiponectin with many chronic diseases. PMID:25648736

Association Between Coffee Consumption and Circulating Levels of Adiponectin and Leptin.

PubMed

Lee, Chang Beom; Yu, Sung Hoon; Kim, Na Yeon; Kim, Seon Mee; Kim, Sung Rae; Oh, Seung Joon; Jee, Sun Ha; Lee, Jung Eun

2017-11-01

Coffee has been proposed to have benefits for chronic diseases; however, the relevant mechanism remains to be elucidated. We conducted a cross-sectional study and evaluated the levels of adiponectin and leptin in relation to coffee consumption. We included a total of 4406 individuals (men = 2587 and women = 1819) for adiponectin analysis and 2922 individuals (men = 1731 and women = 1191) for leptin analysis. Participants answered number of cups of coffee per week and types of coffee they consumed and their serum levels of adiponectin and leptin were measured using an enzyme-linked immunosorbent assay. We found that increasing coffee consumption was associated with increased levels of adiponectin among women; geometric means of adiponectin were 8.0 (95% CI: 7.2-8.9 μg/mL) among women who regularly consumed 15 or greater cups/week, but 7.5 (95% CI: 6.8-8.4 μg/mL) among women who did not consume coffee (P for trend = .009). Leptin levels were inversely associated with coffee consumption among both men and women (P for trend = .04 for men and 0.04 for women); geometric means of 15 or greater cups of coffee per week were 2.6 (95% CI: 2.4-2.8 ng/mL) among men and 5.1 (95% CI: 4.5-5.8 ng/mL) among women, but for noncoffee drinkers, geometric means were 3.0 (95% CI: 2.7-3.3 ng/mL) for men and 5.8 (95% CI: 5.1-6.6 ng/mL) for women. Coffee consumption was associated with higher circulating levels of adiponectin and lower circulating levels of leptin. Our study may suggest that improvement in adipocyte function contributes to the beneficial metabolic effects of coffee consumption.

Sex Dimorphism in Late Gestational Sleep Fragmentation and Metabolic Dysfunction in Offspring Mice

PubMed Central

Khalyfa, Abdelnaby; Carreras, Alba; Almendros, Isaac; Hakim, Fahed; Gozal, David

2015-01-01

Background: Excessive sleep fragmentation (SF) is common in pregnant women. Adult-onset metabolic disorders may begin during early development and exhibit substantial sex dimorphism. We hypothesized that metabolic dysfunction induced by gestational SF in male mice would not be apparent in female littermates. Methods: Body weight and food consumption were measured weekly in male and female offspring after late gestational SF or control sleep (SC). At 20 weeks, plasma leptin, adiponectin, lipid profiles, and insulin and glucose tolerance tests were assessed. Leptin and adiponectin, M1, and M2 macrophage messenger RNA expression and polarity were examined. Adiponectin gene promoter methylation levels in several tissues were assessed. Results: Food intake, body weight, visceral fat mass, and insulin resistance were higher, and adiponectin levels lower in male but not female offspring exposed to gestational SF. However, dyslipidemia was apparent in both male and female offspring exposed to SF, albeit of lesser magnitude. In visceral fat, leptin messenger RNA expression was selectively increased and adiponectin expression was decreased in male offspring exposed to gestational SF, but adiponectin was increased in exposed female offspring. Differences in adipokine expression also emerged in liver, subcutaneous fat, and muscle. Increased M1 macrophage markers were present in male offspring exposed to SF (SFOM) while increased M2 markers emerged in SF in female offspring (SFOF). Similarly, significant differences emerged in the methylation patterns of adiponectin promoter in SFOM and SFOF. Conclusion: Gestational sleep fragmentation increases the susceptibility to obesity and metabolic syndrome in male but not in female offspring, most likely via epigenetic changes. Thus, sleep perturbations impose long-term detrimental effects to the fetus manifesting as sex dimorphic metabolic dysfunction in adulthood. Citation: Khalyfa A, Carreras A, Almendros I, Hakim F, Gozal D. Sex dimorphism in late gestational sleep fragmentation and metabolic dysfunction in offspring mice. SLEEP 2015;38(4):545–557. PMID:25325475

Endometria from Obese PCOS Women with Hyperinsulinemia Exhibit Altered Adiponectin Signaling.

PubMed

García, V; Oróstica, L; Poblete, C; Rosas, C; Astorga, I; Romero, C; Vega, M

2015-11-01

Hyperandrogenemia, hyperinsulinemia, and obesity affect 60-70% of patients with Polycystic Ovarian Syndrome (PCOS), who exhibit an altered endometrial insulin signaling. The aim of the study was to evaluate whether hyperandrogenism, hyperinsulinism, and obesity present in PCOS patients impair the endometrial adiponectin signaling pathway. The ex vivo study was conducted on 27 samples from lean (n=9), obese (n=9), and obese-PCOS (n=9) patients. The in vitro assays were performed in immortalized human endometrial stromal cells stimulated with testosterone, insulin, or testosterone plus insulin. Serum steroid-hormones, adiponectin, glucose, and insulin; body mass index, free androgen index, ISI-Composite, and HOMA were evaluated in the 3 groups. Ex vivo and in vitro gene expression and protein content of adiponectin, AdipoR1, AdipoR2, and APPL1 were determined. Adiponectin serum levels were decreased in obese-PCOS patients compared to lean (78%) and obese (54%) controls (p<0.05). AdipoR1 protein and gene expression were increased in obese group vs. obese-PCOS and lean groups (2-fold, p<0.05). In turn, AdipoR2 protein and mRNA content was similar between the 3 groups. APPL1 protein levels were reduced in endometria from both obese groups, compared to lean group (6-fold, p<0.05). Testosterone plus insulin stimulation of T-HESC and St-T1b leads to a reduction of adiponectin, AdipoR1, AdipoR2, and APPL1 protein content in both endometrial cell lines (p<0.05), whereas, in the presence of testosterone or insulin alone, protein levels were similar to basal. Therefore, endometrial adiponectin-signaling pathway is impaired in hyperandrogenemic and hyperinsulinemic obese-PCOS patients, corroborated in the in vitro model, which could affect endometrial function and potentially the implantation process. © Georg Thieme Verlag KG Stuttgart · New York.

Association of the leptin-to-adiponectin ratio with metabolic syndrome in a sub-Saharan African population.

PubMed

Ayina, Clarisse Noël A; Endomba, Francky Teddy A; Mandengue, Samuel Honoré; Noubiap, Jean Jacques N; Ngoa, Laurent Serge Etoundi; Boudou, Philippe; Gautier, Jean-François; Mbanya, Jean Claude; Sobngwi, Eugene

2017-01-01

Worldwide there is an increased prevalence of metabolic syndrome mainly due to life-style modifications, and Africans are not saved of this situation. Many markers have been studied to predict the risk of this syndrome but the most used are leptin and adiponectin. Data on these metabolic markers are scare in Africa and this study aimed to assess the association between the leptin-to-adiponectin ratio (LAR) with metabolic syndrome in a Cameroonian population. This was a cross-sectional study that included 476 adults among a general population of Cameroon. Data collected concerned the body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, plasma lipids, adiponectin, leptin, insulin and homeostasis model for assessment of insulin resistance (HOMA-IR). To assess correlations we used Spearman's analyses and association of the studied variables with metabolic syndrome were done using binary logistic regression analysis. The leptin to adiponectin ratio was significantly and positively correlated with the body mass index (r = 0.669, p < 0.0001), waist circumference (r = 0.595, p < 0.0001), triglycerides (r = 0.190, p = 0.001), insulin levels (r = 0.333, p < 0.0001) and HOMA-IR (r = 0.306, p < 0.0001). Binary logistic regression analysis revealed that leptin, adiponectin and LAR were significantly associated with metabolic syndrome with respective unadjusted OR of 1.429, 0.468 and 1.502. After adjustment, for age and sex, the associations remained significative; LAR was also found to be significantly associated with metabolic syndrome (OR = 1.573, p value =0.000) as well as lower levels of adiponectin (OR = 0.359, p value =0.000) and higher levels of leptin (OR = 1.469, p value =0.001). This study revealed that LAR is significantly associated with metabolic syndrome in sub-Saharan African population, independently to age and sex.

Gene expression of placental hormones regulating energy balance in small for gestational age neonates.

PubMed

Struwe, Ellen; Berzl, Gabriele M; Schild, Ralf L; Dötsch, Jörg

2009-01-01

Fetal growth restriction is associated with an increased risk for metabolic and cardiovascular disease in later life. To further elucidate mechanisms that might be involved in the process of prenatal programming, we measured the adipokines leptin, resistin, and adiponectin and the GH-releasing hormone ghrelin in the placenta of small for gestational age (SGA) neonates. The control group included 24 placentas of appropriate for gestational age (AGA) newborns, in the study group were 16 placentas of SGA neonates. Gene expression of leptin, resistin, adiponectin, and ghrelin was examined. For hormones showing alterations in gene regulation placental protein expression was measured by Western blot. Placental mRNA expression of leptin was significantly increased in SGA placentas (p=0.0035, related to beta-actin). Protein concentration was increased, as well. There were no differences in placental resistin, adiponectin, or ghrelin gene expressions between SGA neonates and controls. Leptin was the only hormone to demonstrate a significant inverse correlation with birth weight (r=-0.44, p=0.01). Adiponectin correlated significantly with leptin (r=0.53, p=0.0023) and ghrelin (r=0.50, p=0.0045). Placental leptin gene expression and protein concentration showed the expected increase in the SGA group. Leptin was inversely correlated with birth weight. Positive correlation of adiponectin with leptin and ghrelin expression suggests an interaction between these hormones in the placenta. However, the unchanged expression of resistin, adiponectin, and ghrelin in SGA placentas and the absence of correlation with birth weight cast doubt whether these hormones produced in the placenta play a key role in fetal programming.

Relationship between adiponectin and leptin on osteocalcin in obese adolescents during weight loss therapy.

PubMed

Campos, Raquel Munhoz da Silveira; Masquio, Deborah Cristina Landi; Corgosinho, Flávia Campos; Carvalho-Ferreira, Joana Pereira de; Molin Netto, Bárbara Dal; Clemente, Ana Paula Grotti; Tock, Lian; Tufik, Sergio; Mello, Marco Túlio de; Dâmaso, Ana Raimunda

2018-05-17

Obesity is a multifactorial disease characterized by the presence of the pro-inflammatory state associated with the development of many comorbidities, including bone turnover marker alterations. This study aimed to investigate the role of the inflammatory state on bone turnover markers in obese adolescents undergoing interdisciplinary weight loss treatment for one year. Thirty four post-pubescent obese adolescents with primary obesity, a body mass index (BMI) greater than > 95th percentile of the CDC reference growth charts, participated in the present investigation. Measurements of body composition, bone turnover markers, inflammatory biomarkers and visceral and subcutaneous fat were taken. Adolescents were submitted to one year of interdisciplinary treatment (clinical approach, physical exercise, physiotherapy intervention, nutritional and psychological counseling). Reduction in body mass, body fat mass, visceral and subcutaneous fat, as well as, an increase in the body lean mass and bone mineral content was observed. An improvement in inflammatory markers was seen with an increase in adiponectin, adiponectin/leptin ratio and inteleukin-15. Moreover, a positive correlation between the adiponectin/leptin ratio and osteocalcin was demonstrated. Further, both lean and body fat mass were predictors of osteocalcin. Negative associations between leptin with osteocalcin, adiponectin with Beta CTX-collagen, and visceral fat with adiponectin were observed. It is possible to conclude that the inflammatory state can negatively influence the bone turnover markers in obese adolescents. In addition, the interdisciplinary weight loss treatment improved the inflammatory state and body composition in obese adolescents. Therefore, the present findings should be considered in clinical practice.

Combined association of maternal and paternal family history of diabetes with plasma leptin and adiponectin in overweight Hispanic children.

PubMed

Koebnick, C; Kelly, L A; Lane, C J; Roberts, C K; Shaibi, G Q; Toledo-Corral, C M; Davis, J N; Weigensberg, M J; Goran, M I

2008-09-01

To investigate the importance of a maternal and paternal family history of Type 2 diabetes and their combined association with plasma leptin and adiponectin levels in overweight Latino children with a family history of Type 2 diabetes (T2DM). This cross-sectional study investigated the combined association of a maternal and paternal family history of T2DM with leptin and adiponectin in 175 overweight Latino children (age 11.1 +/- 1.7 years). All subjects had a family history of T2DM. Plasma adiponectin and leptin levels, body fat measured by dual-energy X-ray absorptiometry, Tanner stage, age and insulin sensitivity were assessed. After adjustment for age, gestational diabetes, insulin sensitivity and body fat, a combined maternal and paternal family history of T2DM was associated with higher leptin concentrations (P = 0.004) compared with a maternal or paternal family history alone. This association was most pronounced at Tanner stage 1 (P for interaction family history x tanner stage = 0.022). The presence of a combined maternal and paternal family history of T2DM accounted for 4% (P = 0.003) of the variation in leptin concentrations. No such combined association was observed for adiponectin levels. Maternal and paternal family history of T2DM may have an additive impact on leptin, but not on adiponectin levels independent of adiposity and insulin sensitivity in overweight Latino children. This may contribute to a further clinically relevant deterioration of metabolic health in this population.

Higher fetuin-A, lower adiponectin and free leptin levels mediate effects of excess body weight on insulin resistance and risk for myelodysplastic syndrome.

PubMed

Dalamaga, Maria; Karmaniolas, Konstantinos; Chamberland, John; Nikolaidou, Athina; Lekka, Antigoni; Dionyssiou-Asteriou, Amalia; Mantzoros, Christos S

2013-12-01

Excess body weight has been implicated in the pathogenesis of myelodysplastic syndrome (MDS). We thus explored the role of serum fetuin-A reflecting ectopic hepatic fat deposition when storage capacity of adipocytes has been exceeded, free leptin reflecting overall fat mass and adiponectin reflecting visceral fat mass, all potential mediators of the effects of obesity on insulin resistance and, consequently, to MDS risk. In a hospital-based case-control study, we studied 101 cases with incident, histologically confirmed primary MDS and 101 controls matched on gender, age and date of diagnosis, between 2004 and 2007. Serum fetuin-A, adiponectin, leptin, leptin receptor, free leptin and insulin were determined. Higher serum fetuin-A, lower adiponectin and lower free leptin were all individually and independently associated with higher risk of MDS before and after controlling for matching and risk factors, such as age, gender, date of diagnosis, body mass index (BMI), family history of lymphohematopoietic cancer, smoking history and serum insulin. Interestingly, we have shown that these associations were prominent among overweight/obese individuals and persisted after controlling for BMI and serum insulin indicating that their effects are above and beyond insulinemia only. Elevated serum fetuin-A but lower adiponectin and free leptin are associated with higher risk of MDS particularly among overweight/obese individuals. These findings suggest that the association between excessive weight gain and the risk of MDS could be mediated by fetuin-A, adiponectin and free leptin, which may have potential clinical and preventive implications. © 2013.

Correlation between heat shock proteins, adiponectin, and T lymphocyte cytokine expression in type 2 diabetics.

PubMed

Mahmoud, Fadia F; Haines, David; Dashti, Ali A; El-Shazly, Sherief; Al-Najjar, Fawzia

2018-05-11

Type 2 diabetes mellitus (T2DM) features insulin resistance, hyperglycemia, dyslipidemia, overproduction of inflammatory cytokines, and systemic oxidative stress. Here, heat shock proteins Hsp70 and Hsp 90, adiponectin, and heme oxygenase-1 (HO-1, Hsp32) are profiled in peripheral blood mononuclear cells (PBMC) and serum from 25 T2DM patients and 25 healthy control subjects. Cells cultured with phorbol 12-myristate 13-acetate/ionomycin were evaluated by three-color flow cytometry for immunophenotypic biomarkers. Plasma HO-1, Hsp, and adiponectin levels were assayed by enzyme-linked immunosorbent assay (ELISA). Relative to healthy controls, T2DM patients exhibited significantly elevated plasma Hsp70, and representation of T helper immunophenotypes activated to express inflammatory cytokines, including CD4+ IFN-γ+, CD4+ TNF-α+, CD4+ IL-6+, CD4+ IL-1β+ T cells, significantly lower representation of CD4+ IL-10+ T cells, plasma adiponectin and cell-associated HO-1 expression-with no significant differences in plasma Hsp90 between T2DM and healthy controls. Plasma HO-1 and adiponectin in T2DM patients inversely correlated with TNF-α and showed inverse correlation between serum LDL and plasma HO-1. Moreover, TNF-α and Hsp90 in T2DM patients correlated positively with fasting blood glucose (FBG). These results demonstrate correlation between potentially pathogenic T cells, HO-1, and adiponectin, additionally revealing a T helper (Th)1-related character of T2DM immunopathogenesis, suggesting potential for novel T cell-related management strategies for T2DM and related co-morbidities.

An acute intake of a walnut-enriched meal improves postprandial adiponectin response in healthy young adults.

PubMed

Lozano, Aquiles; Perez-Martinez, Pablo; Marin, Carmen; Tinahones, Francisco J; Delgado-Lista, Javier; Cruz-Teno, Cristina; Gomez-Luna, Purificacion; Rodriguez-Cantalejo, Fernando; Perez-Jimenez, Francisco; Lopez-Miranda, Jose

2013-12-01

A deficit in adiponectin plays an important causal role in insulin resistance and metabolic syndrome. We hypothesized that as seen during the fasting state, the intake of a walnut-enriched meal increased postprandial adiponectin. Twenty-one healthy white men followed a 4-week baseline diet and then consumed 3 fat-loaded meals that included 1 g fat/kg body weight (65% fat) according to a randomized crossover design: olive oil-enriched meal (22% saturated fatty acids [SFA], 38% monounsaturated fatty acids [MUFA], 4% polyunsaturated fatty acids [PUFA]), butter-enriched meal (35% SFA, 22% MUFA, 4% PUFA), and walnut-enriched meal (20% SFA, 24% MUFA, 16% PUFA, and 4% α-linolenic acid). Leptin, resistin, adiponectin, and free fatty acids were determined at 0, 3, 6, and 8.5 hours after the fat load. After the walnut-enriched meal, plasma adiponectin concentrations were higher at 3 and 6 hours (P = .011, P = .046, respectively) compared with the butter-enriched meal and higher at 6 hours compared with the olive oil-enriched meal (P = .036). Free fatty acid levels decreased from baseline at 3 hours after the walnut-enriched meal (P = .001). No differences were observed between the 3 meals for leptin and resistin responses. Our data confirmed a beneficial profile in the postprandial response to walnuts, source of omega-3 PUFA with an increased postprandial adiponectin and lower postprandial free fatty acid responses. These findings suggest that the postprandial state is important for understanding the possible cardioprotective effects associated with omega-3 PUFA dietary fat. © 2013 Elsevier Inc. All rights reserved.

Association of Adiponectin rs1501299 and rs266729 Gene Polymorphisms With Nonalcoholic Fatty Liver Disease

PubMed Central

Hashemi, Mohammad; Hanafi Bojd, Hamideh; Eskandari Nasab, Ebrahim; Bahari, Ali; Hashemzehi, Noor Allah; Shafieipour, Sara; Narouie, Behzad; Taheri, Mohsen; Ghavami, Saeid

2013-01-01

Background Genetic and environmental factors are important for the development of nonalcoholic fatty liver disease (NAFLD). Adiponectin is a white and brown adipose tissue hormone, and have been found to play essential roles in the regulation of energy homoeostasis. Recent reports have identified a possible role of adiponectin in NAFLD via PPARγ pathway. Objectives The present study was designed to find out the impact of adiponectin rs1501299 (276G/T) and rs266729 (-11377C/G) gene polymorphisms in NAFLD. Patients and Methods Eighty-three patients with diagnosis of NAFLD, and 93 healthy subjects were included in the study. Tetra ARMS-PCR was designed to detect single nucleotide polymorphisms. Results A significant difference was found between NAFLD and control group regarding the rs266729 polymorphism (χ2 = 7.35, P = 0.025). The rs266729 polymorphism increased the risk of NAFLD in codominant (CC vs. CG: OR = 2.18, 95% CI = 1.16 - 4.12, P = 0.016) and dominant (CC vs. CG/GG: OR = 2.31, 95% CI = 1.25 - 4.27; P = 0.008) inheritance tested models. The G allele increased the risk of NAFLD (OR = 1.63, 95% CI = 1.03 - 2.57, P = 0.037) in comparison with C allele. No significant difference was found between the groups concerning adiponectin rs1501299 gene polymorphism (χ2 = 0.70, P = 0.697). Conclusions adiponectin rs266729 polymorphism might be a candidate gene, which determines the susceptibility to NAFLD. Larger studies are necessary to confirm these findings in various populations. PMID:23922565

Role of adiponectin in the metabolic effects of cannabinoid type 1 receptor blockade in mice with diet-induced obesity

PubMed Central

Godlewski, Grzegorz; Earley, Brian J.; Zhou, Liang; Jourdan, Tony; Szanda, Gergö; Cinar, Resat; Kunos, George

2013-01-01

The adipocyte-derived hormone adiponectin promotes fatty acid oxidation and improves insulin sensitivity and thus plays a key role in the regulation of lipid and glucose metabolism and energy homeostasis. Chronic cannabinoid type 1 (CB1) receptor blockade also increases lipid oxidation and improves insulin sensitivity in obese individuals or animals, resulting in reduced cardiometabolic risk. Chronic CB1 blockade reverses the obesity-related decline in serum adiponectin levels, which has been proposed to account for the metabolic effects of CB1 antagonists. Here, we investigated the metabolic actions of the CB1 inverse agonist rimonabant in high-fat diet (HFD)-induced obese adiponectin knockout (Adipo−/−) mice and their wild-type littermate controls (Adipo+/+). HFD-induced obesity and its hormonal/metabolic consequences were indistinguishable in the two strains. Daily treatment of obese mice with rimonabant for 7 days resulted in significant and comparable reductions in body weight, serum leptin, free fatty acid, cholesterol, and triglyceride levels in the two strains. Rimonabant treatment improved glucose homeostasis and insulin sensitivity to the same extent in Adipo+/+ and Adipo−/− mice, whereas it reversed the HFD-induced hepatic steatosis, fibrosis, and hepatocellular damage only in the former. The adiponectin-dependent, antisteatotic effect of rimonabant was mediated by reduced uptake and increased β-oxidation of fatty acids in the liver. We conclude that reversal of the HFD-induced hepatic steatosis and fibrosis by chronic CB1 blockade, but not the parallel reduction in adiposity and improved glycemic control, is mediated by adiponectin. PMID:24381003

Pioglitazone (7.5 mg/day) added to flutamide-metformin in women with androgen excess: additional increments of visfatin and high molecular weight adiponectin.

PubMed

Ibáñez, Lourdes; López-Bermejo, Abel; Díaz, Marta; Enríquez, Goya; Valls, Carme; de Zegher, Francis

2008-02-01

Low-dose pioglitazone (Pio), flutamide (Flu), metformin (Met) plus an oestro-progestagen is a novel polytherapy lowering total and visceral adiposity, and reducing carotid intima media thickness (IMT) in hyperinsulinaemic women with androgen excess, without changing their body mass index (BMI). In a search for mediators of PioFluMet's actions, we measured serum levels of visfatin and high molecular weight (HMW) adiponectin. In a double-blind study, we enrolled 38 young women with hyperinsulinaemic androgen excess [mean BMI: 23.7 kg/m(2)], all of whom started on Flu (62.5 mg/day), Met (850 mg/day) and a transdermal oestro-progestagen, each for 21/28 days over 1 year. Patients were randomly assigned to receive, in addition, placebo (n = 19) or Pio (7.5 mg/day; n = 19) on the same 21/28 days. Serum concentrations of visfatin and HMW adiponectin, visceral fat by magnetic resonance imaging, carotid IMT by ultrasound, all carried out during study start and after 1 year. PioFluMet raised visfatin by a mean 84% and HMW adiponectin by 157% (P < 0.001), and reduced visceral fat and IMT by a mean 22% and 31% (both P < 0.001). Low-dose Pio accounted for about half of the PioFluMet effects on IMT, visfatin and HMW adiponectin. In hyperinsulinaemic women with androgen excess, low-dose polytherapy with PioFluMet evoked striking rises in both circulating visfatin and HMW adiponectin, while lowering IMT and reducing visceral adiposity within 1 year.

Manganese supplementation increases adiponectin and lowers ICAM-1 and creatinine blood levels in Zucker type 2 diabetic rats, and downregulates ICAM-1 by upregulating adiponectin multimerization protein (DsbA-L) in endothelial cells.

PubMed

Burlet, Elodie; Jain, Sushil K

2017-05-01

Blood and tissue levels of manganese (Mn) are lower in type 2 diabetic and atherosclerosis patients compared with healthy subjects. Adiponectin has anti-diabetic and anti-atherogenic properties. Impairment in Disulfide bond A-like protein (DsbA-L) is associated with low adiponectin levels and diabetes. This study investigates the hypothesis that the beneficial effects of Mn supplementation are mediated by adiponectin and DsbA-L. At 6 weeks of age, Male Zucker diabetic fatty rats (ZDF) were randomly divided into two groups: diabetic controls and Mn-supplemented diabetic rats. Each rat was supplemented with Mn (D+Mn, 16 mg/kg BW) or water (placebo, D+P) daily for 7 weeks by oral gavage. For cell culture studies, Human Umbilical Vein Endothelial Cells (HUVEC) or 3T3L1 adipocytes were pretreated with Mn (0-10 µM MnCl 2 ) for 24 h, followed by high glucose (HG, 25 mM) or normal glucose (5 mM) exposure for another 24 h. Mn supplementation resulted in higher adiponectin (p = 0.01), and lower ICAM-1 (p = 0.04) and lower creatinine (p = 0.04) blood levels compared to those in control ZDF rats. Mn-supplemented rats also caused reduced oxidative stress (ROS) and NADPH oxidase, and higher DsbA-L expression in the liver (p = 0.03) of ZDF rats compared to those in livers of control rats; however, Fe levels in liver were lower but not significant (p = 0.08). Similarly, treatment with high glucose (25 mM) caused a decrease in DsbA-L, which was prevented by Mn supplementation in HUVEC and adipocytes. Mechanistic studies with DsbA-L siRNA showed that the beneficial effects of Mn supplementation on ROS, NOX4, and ICAM-1 expression were abolished in DsbA-L knock-down HUVEC. These studies demonstrate that DsbA-L-linked adiponectin mediates the beneficial effects observed with Mn supplementation and provides evidence for a novel mechanism by which Mn supplementation can increase adiponectin and reduce the biomarkers of endothelial dysfunction in diabetes.

Regulation of adiponectin in adipocytes upon exposure to HIV-1

USDA-ARS?s Scientific Manuscript database

Adipose dysregulation, dyslipidemia, and insulin resistance are hallmarks of HIV-related lipodystrophy. The precise mechanisms behind these disturbances are unknown. In HIV-infected patients, we previously demonstrated a strong relationship between lipodystrophy and levels of adiponectin, an adipose...

[Adiponectin in patients with metabolic syndrome and diseases of the liver, bile ducts and pancreas].

PubMed

Vašura, Adam; Blaho, Martin; Dítě, Petr; Kupka, Tomáš; Svoboda, Pavel; Martínek, Arnošt

Epidemiological data show that the metabolic syndrome can be diagnosed in up to 30 % of the population. Regarding 5 components of the metabolic syndrome, three of them, in case of positivity (visceral obesity, arterial hypertension, hypertriglyceridemia, changes of HDL-cholesterol levels and type 2 diabetes mellitus), are pathogenic factors which are the most frequently related to cardiovascular diseases, but currently they are also the focus of interest for gastroenterologists. The relationship between non-alcoholic hepatic steatosis, including non-alcoholic steatohepatitis, has been described. Less is known so far about the relation to the pancreas disease, particularly with respect to the status referred to as non-alcoholic fatty pancreas disease. The hormone selectively produced by adipose tissue is adiponectin. This protein is studied as a possible biomarker in people with metabolic syndrome, including obesity. Besides that, there is a question studied whether adiponectin can also play a significant role in the pathogenesis of diseases associated with fat building up in parenchymatous organs. Finding a reliable biomarker for patients with metabolic syndrome or diseases of the liver, biliary system and pancreas in relation to metabolic syndrome, presents a big challenge. And adiponectin is one of the promising biomarkers.Key words: adiponectin - biliary disease - metabolic syndrome - pancreatic steatosis - steatohepatitis.

Serum Adiponectin and Leptin Concentrations in Relation to Body Fat Distribution, Hematological Indices and Lipid Profile in Humans.

PubMed

Lubkowska, Anna; Radecka, Aleksandra; Bryczkowska, Iwona; Rotter, Iwona; Laszczyńska, Maria; Dudzińska, Wioleta

2015-09-14

The purpose of the study was to evaluate the relationship between serum adiponectin and leptin concentrations and body composition, hematological indices and lipid profile parameters in adults. The study involved 95 volunteers (BMI from 23.3 to 53 kg/m²). Anthropometric parameters were measured: body weight and height, waist and hip circumference, waist-to-hip ratio, body fat mass (BMF), subcutaneous and visceral fat mass (SFM, VFM), lean body mass (LBM), skeletal muscle mass (SMM). In serum we determined adiponectin and leptin concentrations, extracellular hemoglobin, total bilirubin, as well as lipid metabolism (TCh, HDL-Ch, LDL-Ch, TG). Mean adipokine levels were significantly higher in women (p ≤ 0.01), adiponectin significantly negatively correlated with body height and weight, systolic blood pressure and absolute LBM and SMM values. The same relation was observed for erythroid system indicators and lipid indicators. A positive correlation was exceptionally found between adiponectin and HDL-Ch. LEP negatively correlated with some percentage rates (%LBM, %SMM). Only in women, we observed a positive correlation between LEP and body weight, BMI and WHR. Studies on ADPN and the ADPN/LEP ratio as a valuable complementary diagnostic element in the prediction and prevention of cardiovascular diseases need to be continued.

Adiposity trajectory and its associations with plasma adipokine levels in children and adolescents-A prospective cohort study.

PubMed

Li, Shenghui; Liu, Rong; Arguelles, Lester; Wang, Guoying; Zhang, Jun; Shen, Xiaoming; Wang, Xiaobin

2016-02-01

This study aimed to examine the associations of longitudinal adiposity measures with two adipokines, leptin and adiponectin, and their ratio in children and adolescents. A total of 953 children and adolescents participated in a 6-year longitudinal study. Body mass index (BMI), percentage body fat (%BF), and fat mass index (FMI) were used to assess adiposity status. After adjusting for possible confounders, our regression models revealed that BMI, %BF, and FMI, in both the baseline and follow-up surveys were independently associated with a higher level of leptin and the leptin/adiponectin ratio at the follow-up survey, whereas the significant association with adiponectin only partly existed in adiposity measures at the follow-up visit. Moreover, the longitudinal change in adiposity measures was found to be a significant predictor for follow-up plasma adipokine levels. Compared with the low→low group, the medium→medium group, up-trend group, and high→high group all showed a significantly increased level of leptin and leptin/adiponectin ratio. The up-trend group and high→high group also had significantly decreased adiponectin levels. These findings highlight the importance of adiposity surveillance and the utility of adipokines as biomarkers for adverse metabolic consequences of childhood adiposity. © 2015 The Obesity Society.

Breast milk leptin and adiponectin in relation to infant body composition up to 2 years.

PubMed

Brunner, S; Schmid, D; Zang, K; Much, D; Knoeferl, B; Kratzsch, J; Amann-Gassner, U; Bader, B L; Hauner, H

2015-02-01

Adipokines in breast milk have been associated with infant growth trajectories. We aimed to explore the relationship of leptin and adiponectin in breast milk with infant weight gain and body composition up to the age of 2 years. Breast milk samples were collected from exclusively or partially breastfeeding mothers at 6 weeks (n = 152) and 4 months (n = 120) post-partum. Leptin and adiponectin were determined in skim breast milk and related to infant growth and fat mass assessed by skin-fold thickness measurements. A total of 118 infants were examined at 2 years. The levels of both milk adipokines were slightly lower at 4 months compared with 6 weeks post-partum. Breast milk leptin was largely unrelated to infant anthropometric measures up to 2 years. Milk adiponectin tended to be inversely related to early infant anthropometry up to 4 months, but beyond was positively associated with weight gain and the sum of skin-folds up to 2 years. Our results suggest that higher adiponectin levels in breast milk might be associated with greater weight gain and higher fat mass in the offspring up to 2 years. © 2014 The Authors. Pediatric Obesity © 2014 International Association for the Study of Obesity.

Hypoadiponectinemia, elevated iron and high-sensitivity C-reactive protein levels and their relation with prostate size in benign prostatic hyperplasia.

PubMed

Nandeesha, H; Eldhose, A; Dorairajan, L N; Anandhi, B

2017-09-01

Elevated iron, high-sensitivity C-reactive protein (CRP) and hypoadiponectinemia are known to initiate tumour development. There is paucity of data regarding the above-mentioned parameters and their relation with prostate size in benign prostatic hyperplasia (BPH). The present study was designed to assess the levels of iron, hs-CRP and adiponectin levels and their association with prostate size in BPH patients. A total of 37 BPH cases and 36 controls were enrolled in the study. Iron, hs-CRP and adiponectin were estimated in both the groups. Iron and hs-CRP were significantly increased and adiponectin was significantly reduced in BPH cases when compared with controls. Iron (r = .397, p = .015), hs-CRP (r = .341, p = .039) and adiponectin (r = -.464, p = .004) were significantly associated with prostate size in BPH cases. Multivariate linear regression analysis showed that iron acts as predictor of prostate size in BPH (R 2  = 0.395, β = 0.526, p = .001). We conclude that iron and hs-CRP are elevated and adiponectin is reduced in BPH cases and associated with prostate size. © 2016 Blackwell Verlag GmbH.

The Effect of Vegan Protein-Based Diets on Metabolic Parameters, Expressions of Adiponectin and Its Receptors in Wistar Rats.

PubMed

Chen, Jie-Hua; Song, Jia; Chen, Yan; Ding, Qiang; Peng, Anfang; Mao, Limei

2016-10-18

Vegan protein-based diet has attracted increasing interest in the prevention of metabolic syndrome (MetS). Meanwhile, adiponectin has become a highly potential molecular target in the prevention of MetS. Our study will identify a potential vegan protein diet for the prevention of MetS using rat models. Thirty-six Wistar rats were randomly assigned into three groups and given diets containing one of the following proteins for 12 weeks: casein (CAS, control diet), soy protein (SOY), and gluten-soy mixed protein (GSM). Changes in metabolic parameters as well as the expressions of adiponectin and its receptors were identified. Compared to CAS diet, both SOY and GSM diets led to decreases in blood total cholesterol and triglycerides, but only GSM diet led to an increase in HDL-cholesterol; no marked difference was observed in blood glucose in all three groups; HOMA-IR was found lower only in SOY group. Among groups, the order of serum adiponectin level was found as GSM > SOY > CAS. Similar order pattern was also observed in expression of adiponectin in adipose tissue and AdipoR1 mRNA in skeletal muscle. Our results suggested for the first time that, besides SOY diet, GSM diet could also be a possible substitute of animal protein to prevent MetS.

Metabolic profiling in Prader-Willi syndrome and nonsyndromic obesity: sex differences and the role of growth hormone.

PubMed

Irizarry, Krystal A; Bain, James; Butler, Merlin G; Ilkayeva, Olga; Muehlbauer, Michael; Haqq, Andrea M; Freemark, Michael

2015-12-01

To identify metabolic factors controlling appetite and insulin sensitivity in PWS and assess effects of GH treatment. We compared amino acids, fatty acids and acylcarnitines in GH-treated and untreated PWS children and obese and lean controls to identify biomarkers associated with ghrelin, peptide YY and markers of insulin sensitivity (adiponectin and HOMA-IR). Compared with obese controls (OC), children with PWS had fasting hyperghrelinaemia, hyperadiponectinaemia, hypoinsulinaemia and increased ghrelin/PYY. Hyperghrelinaemia, hyperadiponectinaemia and hypoinsulinaemia were more striking in PWS females than males, and decreases in BCAA were detected only in PWS females. GH-treated PWS subjects had lower leptin and higher IGF-1 and adiponectin than untreated subjects; fasting ghrelin, PYY and insulin levels were comparable. Ghrelin correlated inversely with BCAA in PWS but not OC. Adiponectin correlated negatively with BMIz and HOMA-IR in PWS; in contrast, adiponectin correlated more strongly with BCAA than BMIz or HOMA-IR in OC. BCAA levels were lower in PWS females than OC females and correlated inversely with ghrelin. Low BCAA in PWS females may promote hyperghrelinaemia and hyperphagia, while hyperadiponectinaemia may maintain insulin sensitivity despite excess weight gain. GH treatment may reduce leptin and increase adiponectin, but does not affect fasting ghrelin or PYY. © 2015 John Wiley & Sons Ltd.

Metabolic profiling in Prader-Willi syndrome and non-syndromic obesity: sex differences and the role of growth hormone

PubMed Central

Irizarry, Krystal A.; Bain, James; Butler, Merlin G.; Ilkayeva, Olga; Muehlbauer, Michael; Haqq, Andrea M.; Freemark, Michael

2015-01-01

Objectives To identify metabolic factors controlling appetite and insulin sensitivity in PWS and assess effects of GH treatment. Methods We compared amino acids, fatty acids, and acylcarnitines in GH-treated and untreated PWS children and obese and lean controls to identify biomarkers associated with ghrelin, peptide YY, and markers of insulin sensitivity (adiponectin and HOMA-IR). Results Compared with obese controls (OC), children with PWS had hyperghrelinemia, hyperadiponectinemia, hypoinsulinemia, and increased ghrelin/PYY. Hyperghrelinemia, hyperadiponectinemia, and hypoinsulinemia were more striking in PWS females than males and decreases in BCAA were detected only in PWS females. GH-treated PWS subjects had lower leptin and higher IGF-1 and adiponectin than untreated subjects; ghrelin, PYY, and insulin levels were comparable. Ghrelin correlated inversely with BCAA in PWS but not OC. Adiponectin correlated negatively with BMIz and HOMA-IR in PWS; in contrast, adiponectin correlated more strongly with BCAA than BMIz or HOMA-IR in OC. Conclusions BCAA levels were lower in PWS females than OC females and correlated inversely with ghrelin. Low BCAA in PWS females may promote hyperghrelinemia and hyperphagia, while hyperadiponectinemia may maintain insulin sensitivity despite excess weight gain. GH treatment may reduce leptin and increase adiponectin, but does not affect ghrelin or PYY. PMID:25736874

Pulmonary inflammation induced by subacute ozone is augmented in adiponectin deficient mice: role of IL-17A

PubMed Central

Kasahara, David I.; Kim, Hye Y.; Williams, Alison S.; Verbout, Norah G.; Tran, Jennifer; Si, Huiqing; Wurmbrand, Allison P.; Jastrab, Jordan; Hug, Christopher; Umetsu, Dale T.; Shore, Stephanie A.

2012-01-01

Pulmonary responses to ozone, a common air pollutant, are augmented in obese individuals. Adiponectin, an adipose derived hormone that declines in obesity, has regulatory effects on the immune system. To determine the role of adiponectin in the pulmonary inflammation induced by extended (48–72 h) low dose (0.3 ppm) exposure to ozone, adiponectin deficient (Adipo−/−) and wildtype mice were exposed to ozone or to room air. In wildtype mice, ozone exposure increased total bronchoalveolar lavage (BAL) adiponectin. Ozone induced lung inflammation, including increases in BAL neutrophils, protein (an index of lung injury), IL-6, KC, LIX and G-CSF were augmented in Adipo−/− versus wildtype mice. Ozone also increased IL-17A mRNA expression to a greater extent in Adipo−/− versus wildtype mice. Moreover, compared to control antibody, anti-IL-17A antibody attenuated ozone-induced increases in BAL neutrophils and G-CSF in Adipo−/− but not in wildtype mice, suggesting that IL-17A, by promoting G-CSF release, contributed to augmented neutrophilia in Adipo−/− mice. Flow-cytometric analysis of lung cells revealed that the number of CD45+/F4/80+/IL-17A+ macrophages and γδ T cells expressing IL-17A increased after ozone exposure in wildtype mice, and further increased in Adipo−/− mice. The IL-17+ macrophages were CD11c− (interstitial macrophages), whereas CD11c+ macrophages (alveolar macrophages) did not express IL-17A. Taken together, the data are consistent with the hypothesis that adiponectin protects against neutrophil recruitment induced by extended, low dose ozone exposure by inhibiting the induction and/or recruitment of IL-17A in interstitial macrophages and/or γδ T cells. PMID:22474022

Mediterranean diet cools down the inflammatory milieu in type 2 diabetes: the MÉDITA randomized controlled trial.

PubMed

Maiorino, Maria Ida; Bellastella, Giuseppe; Petrizzo, Michela; Scappaticcio, Lorenzo; Giugliano, Dario; Esposito, Katherine

2016-12-01

Mediterranean-style diets provide cardiovascular benefits and increase insulin sensitivity. There is little evidence that adherence to Mediterranean diet may influence the levels of the inflammatory milieu in type 2 diabetes. The aim of this study was to assess whether Mediterranean diet influences both C-reactive protein (CRP) and adiponectin in newly diagnosed type 2 diabetes, and whether adherence to Mediterranean diet affects their circulating levels. In a two-arm, single-center trial, 215 men and women with newly diagnosed type 2 diabetes were randomized to a Mediterranean diet (n = 108, 54 males and 54 females) or a low-fat diet (n = 107, 52 males and 55 females), with a total follow-up of 8.1 years. At baseline visit and at 1 year, body weight, HOMA index, CRP, and adiponectin and its fractions were assessed. Adherence to the diets was assessed by calculating the Mediterranean-diet score. At 1 year, CPR fell by 37 % and adiponectin rose by 43 % in the Mediterranean diet group, while remaining unchanged in the low-fat diet group. The pattern of adiponectin fractions (high and non-high molecular weight) showed a response similar to that of total adiponectin. Diabetic patients with the highest scores (6-9 points) of adherence to Mediterranean diet had lower circulating CRP level and higher circulating total adiponectin levels than the diabetic patients who scored <3 points on the scale (P = 0.001). The results of this randomized controlled trial demonstrate that Mediterranean diet cools down the inflammatory milieu of type 2 diabetes.

Early Life Adversity Is Associated With Elevated Levels of Circulating Leptin, Irisin, and Decreased Levels of Adiponectin in Midlife Adults

PubMed Central

Joung, Kyoung Eun; Park, Kyung-Hee; Zaichenko, Lesya; Sahin-Efe, Ayse; Thakkar, Bindiya; Brinkoetter, Mary; Usher, Nicole; Warner, Dorothy; Davis, Cynthia R.; Crowell, Judith A.

2014-01-01

Context: Early-life adversity, defined as physical, emotional, or sexual abuse and neglect before 18 years of age, is associated with metabolic syndrome, obesity, and type 2 diabetes mellitus in adult life. However, the underlying mechanism is not fully understood, and whether adipomyokines are associated with early-life adversity independent of other factors such as body mass index, psychosocial risks, and health behaviors is not known. Objectives: The objective of the study was to evaluate the association between early-life adversity and circulating the levels of the adipomyokines such as leptin, adiponectin, and irisin and the inflammatory marker, C-reactive protein (CRP). Design/Subjects/Setting: This study was a cross-sectional study of 95 adults at a university-based research center. We collected venous blood from participants and analyzed serum for leptin, adiponectin, irisin, and CRP. Results: Circulating leptin, irisin, and CRP levels were significantly higher in the highest adversity tertile group compared with low and middle tertile groups (P < .001 for leptin, P = .01 for irisin, and P = .02 for CRP). Adiponectin levels were lower in the highest tertile group compared with the low and middle tertile groups (P = .03). After adjusting for demographic variables, physical activity, diet, current mental health, and body mass index, the associations between early-life adversity leptin, irisin, and did not change. However, adiponectin and CRP levels were no longer significantly related to early life adversity. Conclusion: Early-life adversity is directly associated with elevated circulating leptin and irisin, and indirectly associated with elevated CRP and decreased adiponectin. These findings suggest that these adipomyokines may play a role in the pathogenesis of metabolic abnormality in a population with significant early life adversity. PMID:24650014

A potential determinant role of adiponectin and receptors for the early embryo development in PCOS patients with obesity hinted by quantitative profiling.

PubMed

Zhang, Ning; Hao, Cuifang; Liu, Xiaoyan; Zhang, Shouxin; Zhang, Fengrong; Zhuang, Lili; Zhao, Dongmei

2017-02-01

To identify the quantitative profiling of adiponectin and its receptors (AdipoR1, AdipoR2, and T-cadherin) in cumulus cells (CCs) and to evaluate their roles in the early embryo development of polycystic ovary syndrome (PCOS) patients, in part, with obesity. Fifty-five subjects were divided into two groups according to the body mass index. Oocytes were further inseminated and only mature and normal fertilized oocytes (2PN) were included in this research. Real-time PCR and western blot were performed to identify adiponectin and its receptors in CCs. Adiponectin and receptors were ubiquitously expressed in CCs of PCOS and non-PCOS patients. The level of AdipoR2 in CCs from the oocytes yielding blastocyst after 5/6 days in vitro culture was markedly higher than in those from oocytes could not develop to blastocyst stage after Day 6, for non-obese or obese PCOS patients (0.1647 ± 0.0161 versus 0.0783 ± 0.0385, 0.1948 ± 0.0307 versus 0.1057 ± 0.0236, respectively, p < 0.05). In addition, only in patients with PCOS and concurrent obesity the AdipoR1 in CCs was considerably increased in CC-B + compared with CC-B - subgroup (0.5162 ± 0.0371 versus 0.2448 ± 0.0333, p < 0.01). The development of early embryo was associated with the up-regulation of AdipoR1 and AdipoR2 in PCOS patients. Our results suggested that adiponectin could positively modulate embryo development in humans. Further investigations should be carried out to unlock the crucial role that adiponectin plays in embryo development.

The influence of dietary and supplemental calcium on postprandial effects of a high-fat meal on lipaemia, glycaemia, C-reactive protein and adiponectin in obese women.

PubMed

Ferreira, Thaís da S; Antunes, Vanessa P; Leal, Priscila M; Sanjuliani, Antonio F; Klein, Márcia R S T

2017-10-01

Non-fasting hypertriacylglycerolaemia is a risk factor for CVD and the amount of fat in a meal seems to be the main factor influencing postprandial lipaemia. Although several studies suggest that Ca can increase faecal fat excretion, it is not known whether Ca can decrease postprandial TAG. This study aimed to evaluate the influence of dietary Ca (DC) and supplemental Ca (SC) on lipaemia, glucose metabolism, C-reactive protein (CRP) and adiponectin during postprandial period in obese women challenged with a high-fat meal. In this cross-over controlled trial, sixteen obese women aged 20-50 years were randomly assigned to receive three test meals (approximately 2900 kJ; 48 % fat): high DC (547 mg DC), high SC (HSCM; 500 mg SC-calcium carbonate) and low Ca (42 mg DC). Blood samples were collected in the fasting period and at minutes 120 and 240 after meals to evaluate total cholesterol and fractions, TAG, glucose, insulin, high-sensitivity CRP and adiponectin. Serum levels of TAG and insulin increased significantly after all test meals. Only after HSCM total cholesterol did not present a significant increase and LDL-cholesterol had a significant decrease. Postprandial glucose, HDL-cholesterol, CRP and adiponectin did not present significant changes after the three test meals. The comparative analysis of the effects of the three test meals on serum lipids, glucose, insulin, CRP and adiponectin revealed no significant meal-by-time interaction. These results suggest that in obese women challenged with a high-fat meal DC and SC do not interfere with postprandial lipaemia, glucose metabolism, CRP and adiponectin.

Serum leptin and adiponectin levels in children with type 1 diabetes mellitus - Relation to body fat mass and disease course.

PubMed

Majewska, Katarzyna Anna; Majewski, Dominik; Skowrońska, Bogda; Stankiewicz, Witold; Fichna, Piotr

2016-03-01

Leptin and adiponectin are adipokines presenting a wide range of impacts, including glycemic balance regulations. Insulin is one of the main regulators of adipose tissue function. In type 1 diabetes mellitus (T1DM) endogenous insulin secretion is replaced by the exogenous supply, which is not regulated naturally. The aim of the study was to establish serum leptin and adiponectin levels, and their relations to body fat mass and disease course in children with T1DM. The study included 75 children with T1DM and the control group of 20 healthy coevals. All children had estimated serum leptin and adiponectin concentrations, lipid profile, and bioelectrical impedance analysis. Serum leptin concentrations in children with T1DM were not significantly different from the control group (p=0.067, mean values±SD: 3.11±2.98 vs. 5.29±5.06μg/l, respectively), and related positively to body fat mass in both groups. Adiponectin serum concentrations were significantly higher in children with T1DM than in the control group (p<0.001; mean values: 18.82±9.31 vs. 12.10±5.53μg/ml, respectively), and were not related to the body fat content in the study group. Both, leptin and adiponectin, showed no relation to any of the analyzed parameters of the disease course. Differences observed between children with T1DM and their healthy coevals, when similar in terms of age, body weight, and body fat mass, seem not to depend directly on the disease duration, its metabolic control or insulin supply. Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Effect of Recombinant Human Growth Hormone and Rosiglitazone for HIV-Associated Abdominal Fat Accumulation on Adiponectin and other Markers of Inflammation

PubMed Central

Leung, Vivien; Chiu, Ya-Lin; Kotler, Donald P.; Albu, Jeanine; Zhu, Yuan-Shan; Ham, Kirsis; Engelson, Ellen S.; Hammad, Hoda; Christos, Paul; Donovan, Daniel S.; Ginsberg, Henry N.; Glesby, Marshall J.

2016-01-01

Background/Objective In a previous report of HIV-infected patients with fat redistribution, we found that recombinant human growth hormone (rhGH) therapy reduced visceral adipose tissue (VAT) but increased insulin resistance, and that the addition of rosiglitazone reversed the negative effects of rhGH on insulin sensitivity. In this study, we sought to determine the effects of recombinant human growth hormone (rhGH) and rosiglitazone therapy on an array of inflammatory and fibrinolytic markers. Methods 72 patients with HIV-associated abdominal obesity and insulin resistance were randomized to treatment with rhGH, rosiglitazone, the combination of rhGH and rosiglitazone, or placebo for 12 weeks. Subjects with plasma and serum samples available at weeks 0 (n = 63) and 12 (n = 46-48) were assessed for adiponectin, C-reactive protein (CRP), homocysteine, interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), fibrinogen, plasminogen activator inhibitor-1 (PAI-1) antigen, and tissue plasminogen activator (tPA) antigen. Results Treatment with both rosiglitazone alone and the combination of rosiglitazone and rhGH for 12 weeks resulted in significant increases in adiponectin levels from baseline. Adiponectin levels did not change significantly in the rhGH alone arm. There were no significant changes in the other biomarkers amongst the different treatment groups. Discussion In this study of HIV-infected patients with altered fat distribution, treatment with rosiglitazone had beneficial effects on adiponectin concentrations, an effect that was also seen with combination rosiglitazone and rhGH. RhGH administration alone, however, did not demonstrate any significant impact on adiponectin levels despite reductions in VAT. PMID:27077672

Impact of polyunsaturated vegetable oils on adiponectin levels, glycaemia and blood lipids in individuals with type 2 diabetes: a randomised, double-blind intervention study.

PubMed

Müllner, E; Plasser, E; Brath, H; Waldschütz, W; Forster, E; Kundi, M; Wagner, K-H

2014-10-01

Low adiponectin levels are discussed as risk factor for cardiovascular events. This is of special importance in individuals with type 2 diabetes (T2DM) because they are at higher risk for cardiovascular diseases. The present study aimed to investigate the effect of two plant oils rich in polyunsaturated fatty acids (PUFA), with different content of omega-3 fatty acids, on adiponectin levels, glucose and lipid metabolism in T2DM individuals treated either with insulin or oral anti-diabetics (OAD). Ninety-two subjects with T2DM [34 treated with insulin (T2DM-Ins) and 58 treated with OAD (T2DM-OAD)] participated in this randomised, double-blind, parallel intervention study. Individuals received either 9 g of nut oil (n-3:n-6 ratio: 1.3 : 6.1) or mixed oil (n-3:n-6 ratio: 0.6 : 5.7) per day for 10 weeks. The fatty acid profile, tocopherol, adiponectin levels and parameters regarding glucose and lipid metabolism were assessed at baseline, during and after the intervention. Compliance was confirmed by significant increases in γ-tocopherol and PUFA in both oil groups. An increase in adiponectin levels in T2DM-Ins participants (+6.84% in nut oil and +4.47% in mixed oil group after 10 weeks compared to baseline) was observed, albeit not significantly different from T2DM-OAD individuals (P = 0.051). Lipid and glucose metabolism were not affected by the intervention. The present study provides evidence that a small and easy change in dietary behaviour towards better fat quality moderately increases adiponectin levels in T2DM-Ins subjects, independently of the administered plant oil. © 2013 The British Dietetic Association Ltd.

Analysis of the associations among Helicobacter pylori infection, adiponectin, leptin, and 10-year fracture risk using the fracture risk assessment tool: A cross-sectional community-based study

PubMed Central

Chen, Fang-Ping; Hsieh, Chia-Wen; Kuo, Sheng-Fong; Chien, Rong-Nan

2017-01-01

Helicobacter pylori (H. pylori) infection may induce inflammatory cytokines or adipokines that influence bone turnover and bone fracture risk. This study aimed to evaluate the association among H. pylori infection, adipokines, and 10-year fracture risk using the Fracture Risk Assessment Tool scale. From August 2013 to February 2016, a community-based cohort was surveyed by Keelung Chang-Gung Memorial Hospital. Subjects were included if they were older than 40 years and not pregnant. All participants underwent a standardized questionnaire survey, physical examination, urea breath test, and blood tests. A total of 2,689 participants (1,792 women) were included in this cross-sectional study. In both sexes, participants with a high fracture risk were older and had higher adiponectin values than participants without a high fracture risk (mean age, female: 72.9 ± 5.6 vs. 55.8 ± 7.3 years, P < 0.0001; male: 78.9 ± 4.7 vs. 58.1 ± 8.9 years, P < 0.001) (adiponectin, female: 10.8 ± 6.3 vs. 8.7 ± 5.2 ng/ml, P < 0.001; male: 9.7 ± 6.1 vs. 5.5 ± 3.8 ng/ml, P < 0.001). Adiponectin was correlated with high fracture risk in both sexes, but H. pylori infection and leptin was not. In logistic regression analysis, adiponectin could not predict high fracture risk when adjusting the factor of body mass index (BMI) in men group. In conclusion, H. pylori infection and leptin could not predict 10-year fracture risk in either sex. Adiponectin was correlated with bone fracture risk in both sexes and the correlation might be from the influence of BMI. PMID:28388631

No effect of modest selenium supplementation on insulin resistance in UK pregnant women, as assessed by plasma adiponectin concentration.

PubMed

Mao, Jinyuan; Bath, Sarah C; Vanderlelie, Jessica J; Perkins, Anthony V; Redman, Christopher W G; Rayman, Margaret P

2016-01-14

Concern has been expressed recently that Se may increase the risk of type 2 diabetes, but this has not been tested in a randomised-controlled trial (RCT) in pregnant women. We took advantage of having stored plasma samples from the Se in Pregnancy Intervention (SPRINT) RCT of Se supplementation in pregnancy to test the effect of Se supplementation on a marker of insulin resistance in UK pregnant women. Because our blood samples were not fasted, we measured plasma adiponectin concentration, a recognised marker of insulin resistance that gives valid measurements in non-fasted samples, as diurnal variability is minor and there is no noticeable effect of food intake. In SPRINT, 230 primiparous UK women were randomised to treatment with Se (60 μg/d) or placebo from 12 weeks of gestation until delivery. We hypothesised that supplementation with Se at a nutritional level would not exacerbate the fall in adiponectin concentration that occurs in normal pregnancy, indicating the lack of an adverse effect on insulin resistance. Indeed, there was no significant difference between the two groups in the change in adiponectin from 12 to 35 weeks (P=0·938), nor when the analysis was restricted to the bottom or top quartiles of baseline whole-blood Se (P=0·515 and 0·858, respectively). Cross-sectionally, adiponectin concentration was not associated with any parameter of Se status, either at 12 or 35 weeks. It is reassuring that a nutritional dose of Se had no adverse effect on the concentration of adiponectin, a biomarker of insulin resistance, in pregnant women of modest Se status.

Long-Term Dietary Sodium Restriction Increases Adiponectin Expression and Ameliorates the Proinflammatory Adipokine Profile in Obesity

PubMed Central

Baudrand, R; Lian, CG; Lian, BQ; Ricchiuti, V; Yao, TM; Li, J; Williams, GH; Adler, GK

2015-01-01

Background/Aim Obesity is associated with changes in adiponectin and pro-inflammatory adipokines. Sodium intake can affect adipokine secretion suggesting a role in cardiovascular dysfunction. We tested if long-term dietary sodium restriction modifies the expression of adiponectin and ameliorates the pro-inflammatory profile of obese, diabetic Methods/Results Db/db mice were randomized to high sodium (HS 1.6% Na+, n=6) or low sodium (LS 0.03% Na+, n=8) diet for 16 weeks and compared with lean, db/+ mice on HS diet (n=8). Insulin levels were 50% lower in the db/db mice on LS diet when compared with HS db/db (p <0.05). LS diet increased cardiac adiponectin mRNA levels in db/db mice by 5-fold when compared with db/db mice on HS diet and by 2-fold when compared with HS lean mice (both p < 0.01). LS diet increased adiponectin in adipose tissue compared with db/db mice on HS diet, achieving levels similar to those of lean mice. MCP-1, IL-6 and TNF-α expression were reduced more than 50% in adipose tissue of db/db mice on LS diet when compared with HS db/db mice (all p < 0.05), to levels observed in the HS lean mice. Further, LS db/db mice had significantly reduced circulating MCP-1 and IL-6 levels when compared with HS db/db mice (both p < 0.01). Conclusion In obese-diabetic mice, long-term LS diet increases adiponectin in heart and adipose tissue and reduces pro-inflammatory factors in adipose tissue and plasma. These additive mechanisms may contribute to the potential cardioprotective benefits of LS diet in obesity-related metabolic disorders. PMID:24418377

Association study of the HTR2C, leptin and adiponectin genes and serum marker analyses in clozapine treated long-term patients with schizophrenia.

PubMed

Klemettilä, J-P; Kampman, O; Seppälä, N; Viikki, M; Hämäläinen, M; Moilanen, E; Mononen, N; Lehtimäki, T; Leinonen, E

2015-02-01

Clozapine treatment is associated with weight gain and cardio-metabolic consequences among patients with schizophrenia. Polymorphisms of leptin, serotonin receptor HTR2C and adiponectin genes have been associated with antipsychotic-induced weight gain and metabolic comorbidity. However, the results of the studies so far are inconclusive. The aim of the present study was first to test for a possible role of serum leptin and adiponectin levels as a marker of weight gain in association with inflammatory cytokines/adipokines (IL-6, IL-1Ra, hs-CRP and adipsin), and second to study associations between SNPs LEP rs7799039 (-2548 A/G), ADIPOQ rs1501299 and HTR2C rs1414334 and weight gain and levels of leptin and adiponectin, in 190 patients with schizophrenia on clozapine treatment, with retrospectively assessed weight change and cross-sectionally measured cytokine levels. A strong association was found between serum levels of leptin and weight gain and cytokines/adipokines related to metabolic comorbidity, especially among female patients (in women leptin vs. weight gain, IL-6 and IL-1Ra, P<0.001; in men leptin vs. weight gain, P=0.026, leptin vs. IL-1Ra, P<0.001). In male patients low adiponectin level was a more specific marker of clozapine-induced weight gain (P=0.037). The results of the present study do not support a major role of SNPs LEP rs7799039, ADIPOQ rs1501299 and HTR2C rs1414334 in the regulation of weight gain or association of serum levels of leptin and adiponectin and corresponding studied SNPs in patients with schizophrenia on clozapine treatment. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Six months training alone or combined with diet alters HOMA-AD, HOMA-IR and plasma and adipose tissue adiponectin in obese women.

PubMed

Lakhdar, Nadia; Denguezli, Myriam; Zaouali, Monia; Zbidi, Abdelkrim; Tabka, Zouhair; Bouassida, Anissa

2014-01-01

We investigate the effect of 6 months aerobic training alone or in combination with diet on adiponectin in circulation and in adipose abdominal tissue (AT) in obese women. Twenty obese subjects were randomized into a 24 weeks intervention: 1) training (TR) and 2) training and diet (TRD). Blood samples were collected at baseline, after 12 wk and 24 wk. AT biopsies were obtained only at baseline and after 24 wk. In the TRD group the fat loss was after 12 wk -13.74% (p<0.01) and after 24 wk -21.82% (p<0.01) with no changes in the TR group. After 12 and 24 wk, VO2max was increased by 21.81-39.54% (p<0.05) in the TRD group and 18.09-40.95% in the TR group (p<0.05). After 12 wk, plasma adiponectin was raised only in the TRD group (55.8%, p<0.05). After 24 weeks, circulating adiponectin was elevated by 110.4% (p<0.01) in the TRD group and by 27% (p<0.05) in the TR group. In AT biopsies, subjects in the TRD and TR groups exhibited a significant increase in adiponectin (p<0.05 and p<0.01, respectively). The two indices HOMA-IR and HOMA-AD for assessing insulin resistance were strongly affected by protocols. HOMA-IR decreased (p<0.05) only after 24 wk in the TRD group. HOMA-AD increased in both groups after 12 (p<0.05) and 24 wk (p<0.01). Six months chronic aerobic exercise alone or combined with diet result in a significant increase in circulating and adipose tissue adiponectin levels in obese women independent of changes in body composition and/or in HOMA-IR.

Plasma klotho levels decrease in both anorexia nervosa and obesity.

PubMed

Amitani, Marie; Asakawa, Akihiro; Amitani, Haruka; Kaimoto, Kaori; Sameshima, Nanami; Koyama, Ken Ichiro; Haruta, Izumi; Tsai, Minglun; Nakahara, Toshihiro; Ushikai, Miharu; Cheng, Kai-Chun; Hamada, Satoshi; Inui, Akio

2013-09-01

The aim of this study was to examine the associations of klotho with body mass index (BMI) in patients with restricting-type anorexia nervosa (r-AN) and obesity. We examined plasma klotho as well as adiponectin and its isoform levels in comparison in 11 obese patients, 12 r-AN patients, and 11 control participants. Plasma klotho levels were markedly lower in the obesity and r-AN groups than in the control group. Moreover, plasma klotho levels increased significantly after the recovery of BMI in r-AN patients. Total and high-molecular-weight adiponectin levels were significantly decreased only in obesity. There was no relationship between klotho and total adiponectin levels or klotho and respective adiponectin isoform levels in the entire study population. These results suggest that klotho may reflect normal nutritional state, and that the decrease of klotho in r-AN and obesity may underlie the deteriorating processes of these disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Circulating adiponectin levels in type 2 diabetes mellitus patients with or without non-alcoholic fatty liver disease: Results of a small, open-label, randomized controlled intervention trial in a subgroup receiving short-term exenatide.

PubMed

Savvidou, Savvoula; Karatzidou, Kyparissia; Tsakiri, Kalliopi; Gagalis, Asterios; Hytiroglou, Prodromos; Goulis, John

2016-03-01

Diabetes mellitus type 2 (DMT2) and non-alcoholic fatty liver disease (NAFLD) are both characterized by decreased circulating adiponectin. Recently, glucagon-like peptide-1 receptor agonists have been shown to induce adiponectin's expression. However, their interaction on clinical grounds needs to be further elucidated. DMT2 patients with abnormal aminotransferases were screened for NAFLD and subjected to liver biopsy (group A, n=17). A subgroup of patients (n=110), after assessed for eligibility criteria, was blindly randomized to receive either 6-month exenatide supplementation on glargine insulin (group B) or intense, self-regulated, insulin therapy alone (group C). Baseline patient characteristics: 49(38.6%) males, aged 63.1 ± 7.5 years-old, BMI 32.9 ± 4.9 kg/m(2), HbA1c 8.1 ± 1.2% (65 ± 14 mmol/mol), median ALT 23 U/L (range 5-126), AST 20 U/L (7-72). Group A had biopsy-proven NAFLD with a median Activity Score of 5 and fibrosis stage 3. Presence of NAFLD was accompanied by a significant decline in adiponectin (p<0.001), which was negatively correlated with the degree of ALT in all groups (Spearman's correlation, rs=-0.644, p<0.001). In the subgroup intervention trial, adiponectin was significantly raised in both groups B and C (t-Student for paired samples, p=0.001) by Δ=+24.2% (interquartile range 14.8-53.2%). This elevation was not associated with the type of intervention but with weight loss, glycemic control and reduction of C-reactive protein (one-way ANCOVA). Supplementation of exenatide to glargine insulin compared to standard insulin was: (i) effective in inducing weight loss, (ii) non-inferior in lowering HbA1c and (iii) non-inferior in increasing circulating adiponectin. Higher adiponectin was associated with lower ALT, suggesting a hepato-protective role for this cytokine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Attenuated improvements in adiponectin and fat loss characterize type 2 diabetes non-remission status after bariatric surgery.

PubMed

Malin, S K; Bena, J; Abood, B; Pothier, C E; Bhatt, D L; Nissen, S; Brethauer, S A; Schauer, P R; Kirwan, J P; Kashyap, S R

2014-12-01

To identify the metabolic determinants of type 2 diabetes non-remission status after bariatric surgery at 12 and 24 months. A total of 40 adults [mean ± sd body mass index 36 ± 3 kg/m(2) , age 48 ± 9 years, glycated haemoglobin (HbA1c) 9.7 ± 2%) undergoing bariatric surgery [Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG)] were enrolled in the present study, the Surgical Treatment and Medication Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial. Type 2 diabetes remission was defined as HbA1c <6.5% and fasting glucose <126 mg/dl (i.e. <7 mmol/l) without antidiabetic medication. Indices of insulin secretion and sensitivity were calculated from plasma glucose, insulin and C-peptide values during a 120-min mixed-meal tolerance test. Body fat, incretins (glucagon-like polypeptide-1, gastric inhibitory peptide, ghrelin) and adipokines [adiponectin, leptin, tumour necrosis factor-α, high-sensitivity C-reactive protein (hs-CRP)] were also assessed. At 24 months, 37 patients had available follow-up data (RYGB, n = 18; SG, n = 19). Bariatric surgery induced type 2 diabetes remission rates of 40 and 27% at 12 and 24 months, respectively. Total fat/abdominal fat loss, insulin secretion, insulin sensitivity and β-cell function (C-peptide0-120 /glucose0-120 × Matsuda index) improved more in those with remission at 12 and 24 months than in those without remission. Incretin levels were unrelated to type 2 diabetes remission, but, compared with those without remission, hs-CRP decreased and adiponectin increased more in those with remission. Only baseline adiponectin level predicted lower HbA1c levels at 12 and 24 months, and elevated adiponectin correlated with enhanced β-cell function, lower triglyceride levels and fat loss. Smaller rises in adiponectin level, a mediator of insulin action and adipose mass, characterize type 2 diabetes non-remission up to 2 years after bariatric surgery. Adjunctive strategies promoting greater fat loss and/or raising adiponectin may be key to achieving higher type 2 diabetes remission rates after bariatric surgery. © 2014 John Wiley & Sons Ltd.

Fatty acids derived from a food frequency questionnaire and measured in the erythrocyte membrane in relation to adiponectin and leptin concentrations.

PubMed

Santos, S; Oliveira, A; Pinho, C; Casal, S; Lopes, C

2014-05-01

Evidence on the association between fatty acids and adiponectin and leptin concentrations is scarce and inconsistent, which may in part be due to limitations of dietary reporting methods. We aimed to estimate the association of fatty acids, derived from a food frequency questionnaire (FFQ) and measured in the erythrocyte membrane, with adiponectin and leptin concentrations. We studied 330 non-institutionalized inhabitants of Porto (52.4% women; age range: 26-64 years) evaluated in 2010-2011, as part of the EPIPorto cohort study. Fatty acids were derived from a validated semiquantitative FFQ and measured in the erythrocyte membrane by gas chromatography. Serum concentrations of adiponectin and leptin were determined through radioimmunoassay. Regression coefficients (β) and 95% confidence intervals (95% CI) were obtained from linear regression models, after controlling for gender, age, education, leisure time physical activity and total body fat percentage (obtained from dual energy X-ray absorptiometry). Fatty acids measured by FFQ showed no significant associations with both adipokines. Lauric and linoleic acids, measured in the erythrocyte membrane, were significantly and positively associated with adiponectin (β=0.292, 95% CI: 0.168-0.416; β=0.150, 95% CI: 0.020-0.280) and leptin (β=0.071, 95% CI: 0.003-0.138; β=0.071, 95% CI: 0.002-0.140), whereas total n-3, eicosapentaenoic and docosahexaenoic acids were significantly but negatively associated with adiponectin (β=-0.289, 95% CI: -0.420 to -0.159; β=-0.174, 95% CI -0.307 to -0.040; β=-0.253, 95% CI -0.383 to -0.124) and leptin (β=-0.151, 95% CI: -0.220 to -0.083; β=-0.080, 95% CI: -0.151 to -0.009; β=-0.146, 95% CI: -0.214 to -0.078). Positive significant associations of palmitic and trans-fatty acids with adiponectin were also observed. A positive association of lauric and linoleic acids and a negative association of total n-3 fatty acids with both adipokines were observed only with fatty acids measured in the erythrocyte membrane.

Leptin but not adiponectin is related to type 2 diabetes mellitus in obese adolescents.

PubMed

Reinehr, Thomas; Woelfle, Joachim; Wiegand, Susanna; Karges, Beate; Meissner, Thomas; Nagl, Katrin; Holl, Reinhard W

2016-06-01

Adipokines have been suggested to be involved in the development of type 2 diabetes mellitus (T2DM). However, studies in humans are controversial and analyzes at the onset of disease are scarce. We compared adiponectin and leptin levels between 74 predominately Caucasian adolescents with T2DM and 74 body mass index (BMI)-, age-, and gender-matched controls without T2DM. Adiponectin and leptin were correlated to age, BMI, hemoglobin A1c (HbA1c), blood pressure, and lipids. Adolescents with T2DM showed significant lower leptin levels as compared with controls (18 ± 12 vs. 37 ± 23 ng/mL, p < 0.001), whereas the adiponectin levels did not differ between the adolescents with and without T2DM (5.0 ± 2.5 vs. 4.9 ± 2.5 µg/mL, p = 0.833). The associations between adiponectin and high-density lipoprotein (HDL) cholesterol (r = 0.42), systolic (r = -0.15), and diastolic blood pressure (r = -0.20) were stronger as the associations of leptin to these parameters (all r < 0.07). In multiple linear regression analysis, leptin was significantly and positively associated with BMI [β-coefficient: 1.3 (95% confidence interval (95% CI): ±0.5), p < 0.001] and female sex [β-coefficient: 9.7 (95% CI: ±6.7), p = 0.005], and negatively with age [β-coefficient: -2.3 (95% CI: ±2.1), p < 0.001] and HbA1c [β-coefficient -3.1 (95% CI: ±2.1), p = 0.011]. Adiponectin was not significantly associated with BMI, HbA1c, age, or gender in multiple linear regression analysis. Because adiponectin levels did not differ between obese adolescents with and without T2DM, hypoadiponectinemia as observed in obesity seems not to be involved in the genesis of T2DM. The relative hypoleptinemia in obese adolescents with T2DM as compared with obese adolescents without T2DM may contribute to the development of T2DM. Future longitudinal studies in humans are necessary to prove this hypothesis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Circulating leptin and adiponectin are associated with insulin resistance in healthy postmenopausal women with hot flashes

PubMed Central

Huang, Wan-Yu; Chang, Chia-Chu; Chen, Dar-Ren; Kor, Chew-Teng; Chen, Ting-Yu; Wu, Hung-Ming

2017-01-01

Introduction Hot flashes have been postulated to be linked to the development of metabolic disorders. This study aimed to evaluate the relationship between hot flashes, adipocyte-derived hormones, and insulin resistance in healthy, non-obese postmenopausal women. Participants and design In this cross-sectional study, a total of 151 women aged 45–60 years were stratified into one of three groups according to hot-flash status over the past three months: never experienced hot flashes (Group N), mild-to-moderate hot flashes (Group M), and severe hot flashes (Group S). Variables measured in this study included clinical parameters, hot flash experience, fasting levels of circulating glucose, lipid profiles, plasma insulin, and adipocyte-derived hormones. Multiple linear regression analysis was used to evaluate the associations of hot flashes with adipocyte-derived hormones, and with insulin resistance. Settings The study was performed in a hospital medical center. Results The mean (standard deviation) of body-mass index was 22.8(2.7) for Group N, 22.6(2.6) for Group M, and 23.5(2.4) for Group S, respectively. Women in Group S displayed statistically significantly higher levels of leptin, fasting glucose, and insulin, and lower levels of adiponectin than those in Groups M and N. Multivariate linear regression analysis revealed that hot-flash severity was significantly associated with higher leptin levels, lower adiponectin levels, and higher leptin-to-adiponectin ratio. Univariate linear regression analysis revealed that hot-flash severity was strongly associated with a higher HOMA-IR index (% difference, 58.03%; 95% confidence interval, 31.00–90.64; p < 0.001). The association between hot flashes and HOMA-IR index was attenuated after adjusting for leptin or adiponectin and was no longer significant after simultaneously adjusting for leptin and adiponectin. Conclusion The present study provides evidence that hot flashes are associated with insulin resistance in postmenopausal women. It further suggests that hot flash association with insulin resistance is dependent on the combination of leptin and adiponectin variables. PMID:28448547

High-molecular weight adiponectin/HOMA-IR ratio as a biomarker of metabolic syndrome in urban multiethnic Brazilian subjects

PubMed Central

de Abreu, Virgínia Genelhu; Martins, Cyro José de Moraes; de Oliveira, Patricia Aguiar Cardoso; Francischetti, Emilio Antonio

2017-01-01

Metabolic syndrome (MetS) has an important epidemiological relevance due to its increasing prevalence and association with type 2 diabetes and cardiovascular disease. Insulin resistance is a core feature of the MetS. HOMA-IR is a robust clinical and epidemiological marker of MetS. Adiponectin is an adipokine with insulin-sensitizing and anti-inflammatory functions; its levels decrease as number of components of MetS increases. High-molecular weight adiponectin (HMWA) is the multimer responsible for the relationship of adiponectin with insulin sensitivity. HOMA-IR and HMWA are suitable candidates for MetS biomarkers. The ratio of adiponectin to HOMA-IR has been validated as a powerful index of MetS and considered a better marker of its presence, than either HOMA-IR or adiponectin alone, in selected homogeneous populations. We compared the strength of association between HMWA, HOMA-IR and HMWA/HOMA-IR ratio with MetS and its key components. Our data have shown that the median (25th, 75th percentile) of HMWA/HOMA-IR ratio was lower in subjects with MetS [0.51 (0.33, 1.31)] as compared to those without it [2.19 (1.13, 4.71)]. The correlation coefficient (r) was significantly higher for HMWA/HOMA-IR ratio as compared to HMWA for waist circumference (-0.65; -0.40, respectively); mean blood pressure (-0.27; -0.14, respectively); fasting glucose (-0.38; -0.19, respectively); HDL-cholesterol (0.44; 0.40, respectively); and triglycerides (-0.35; -0.18, respectively). In a multivariable logistic regression analysis, the HMWA/HOMA-IR ratio was a sensitive predictor for MetS, being the only marker that was significantly associated with each and all the individual components of the syndrome. These results expand on previous studies in that we used the active circulating form of adiponectin, i.e. HMWA, and represent a typical Brazilian cohort characterized by intense interethnic admixture. Thus, the HMWA/HOMA-IR ratio is a minimally invasive biomarker for MetS that could be clinically useful in prognosing patient outcome. PMID:28746378

High-molecular weight adiponectin/HOMA-IR ratio as a biomarker of metabolic syndrome in urban multiethnic Brazilian subjects.

PubMed

de Abreu, Virgínia Genelhu; Martins, Cyro José de Moraes; de Oliveira, Patricia Aguiar Cardoso; Francischetti, Emilio Antonio

2017-01-01

Metabolic syndrome (MetS) has an important epidemiological relevance due to its increasing prevalence and association with type 2 diabetes and cardiovascular disease. Insulin resistance is a core feature of the MetS. HOMA-IR is a robust clinical and epidemiological marker of MetS. Adiponectin is an adipokine with insulin-sensitizing and anti-inflammatory functions; its levels decrease as number of components of MetS increases. High-molecular weight adiponectin (HMWA) is the multimer responsible for the relationship of adiponectin with insulin sensitivity. HOMA-IR and HMWA are suitable candidates for MetS biomarkers. The ratio of adiponectin to HOMA-IR has been validated as a powerful index of MetS and considered a better marker of its presence, than either HOMA-IR or adiponectin alone, in selected homogeneous populations. We compared the strength of association between HMWA, HOMA-IR and HMWA/HOMA-IR ratio with MetS and its key components. Our data have shown that the median (25th, 75th percentile) of HMWA/HOMA-IR ratio was lower in subjects with MetS [0.51 (0.33, 1.31)] as compared to those without it [2.19 (1.13, 4.71)]. The correlation coefficient (r) was significantly higher for HMWA/HOMA-IR ratio as compared to HMWA for waist circumference (-0.65; -0.40, respectively); mean blood pressure (-0.27; -0.14, respectively); fasting glucose (-0.38; -0.19, respectively); HDL-cholesterol (0.44; 0.40, respectively); and triglycerides (-0.35; -0.18, respectively). In a multivariable logistic regression analysis, the HMWA/HOMA-IR ratio was a sensitive predictor for MetS, being the only marker that was significantly associated with each and all the individual components of the syndrome. These results expand on previous studies in that we used the active circulating form of adiponectin, i.e. HMWA, and represent a typical Brazilian cohort characterized by intense interethnic admixture. Thus, the HMWA/HOMA-IR ratio is a minimally invasive biomarker for MetS that could be clinically useful in prognosing patient outcome.

The effect of n-3 PUFAs on circulating adiponectin and leptin in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Farimani, Azam Rezaei; Hariri, Mitra; Azimi-Nezhad, Mohsen; Borji, Abasalt; Zarei, Sadegh; Hooshmand, Elham

2018-02-16

N-3 PUFAs can potentially influence levels of inflammatory and non-inflammatory adipokines. Given the contradictory effects of n-3 PUFAs on serum levels of adipokines in type 2 diabetes, we conducted a systematic review and meta-analysis study of randomized placebo-controlled clinical trials that examined the effects of n-3 PUFAs on serum levels of leptin and adiponectin in patients with type 2 diabetes. The electronic databases, without regard to language restrictions including PubMed/Medline, Google Scholar, SCOPUS and ISI Web of Science until August 2017, were used to identify randomized controlled trials that assessed the effect of n-3 PUFAs on serum leptin and adiponectin concentrations in type 2 diabetes. Outcomes were extracted based on the mean ± SD as effect size at baseline and end of the intervention. Between-study heterogeneity was evaluated by the I 2 estimates and their 95% CIs. Funnel plot asymmetry was used to investigate the existence of publication bias. Stata software and Review Manager were used for statistical data analysis. Data from 10 eligible articles involved 494 subjects with type 2 diabetes mellitus (intervention groups = 254 and control groups = 240), with age between 44 and 70 years, treated with doses of 0.52-7.4 g/day n-3 PUFAs. Adiponectin concentration nonsignificantly increased by a MD = 0.17 µg/mL (95% CI - 0.11, 0.44). Also, leptin concentration nonsignificantly reduced by a MD = - 0.31 ng/mL (95% CI - 0.69, 0.07). Plant and marine sources of n-3 PUFAs can modify serum leptin and adiponectin levels by increasing adiponectin and decreasing leptin levels in patients with type 2 diabetes. Due to some limitations in this study, further studies are needed to reach a definitive conclusion about the effect of n-3 PUFAs on the levels of leptin and adiponectin in T2DM.

Effects of losartan/hydrochlorothiazide treatment, after change from ARB at usual dosage, on blood pressure and various metabolic parameters including high-molecular weight adiponectin in Japanese male hypertensive subjects.

PubMed

Hirose, Hiroshi; Kawabe, Hiroshi; Saito, Ikuo

2011-01-01

Losartan, an angiotensin II receptor blocker (ARB), has been reported to increase serum level of high-molecular weight (HMW) adiponectin, which has beneficial effects on insulin resistance and atherosclerosis. On the other hand, treatment with diuretics was reported to decrease the adiponectin level. In the present study, we investigated the effects of changing the treatment to losartan/hydrochlorothiazide (HCTZ) on blood pressure (BP) and various metabolic parameters in Japanese male hypertensive subjects. This study included 15 subjects whose therapy was changed from a usual dosage of ARB to losartan 50mg/HCTZ 12.5mg daily, and also 14 subjects who continued losartan treatment (50mg/day). Serum HMW-adiponectin concentration was assayed using a commercially available HMW-specific ELISA kit. In the losartan/HCTZ patient group, systolic/diastolic BP decreased from 146/95 to 130/84 mmHg (P = 0.0012 for both). The HbA1c level tended to increase from 5.44 ± 0.39 to 5.55 ± 0.44% (P = 0.0554) and serum creatinine level slightly increased from 0.82 ± 0.12 to 0.87 ± 0.12 mg/dl (P = 0.0015). In contrast, serum TG (125 ± 77 to 149 ± 112 mg/dl), uric acid, and HMW-adiponectin levels (3.24 ± 2.97 to 3.36 ± 2.43 μg/ml) were unchanged. In the 14 patients who continued losartan treatment, systolic/diastolic BP was unchanged from 134/86 to 129/80 mmHg. The HbA1c level tended to increase from 5.26 ± 0.63 to 5.39 ± 0.71% (P = 0.0880), serum creatinine and uric acid levels were unchanged, serum lipids tended to improve, and serum HMW-adiponectin levels increased from 3.03 ± 1.06 to 3.46 ± 1.28 μg/ml (P = 0.0105). In summary, changing treatment to losartan/HCTZ, when changed from a usual dosage of ARB, exerted good BP control, while the HMW-adiponectin level was unchanged in male hypertensive subjects.

Impact of statin therapy on plasma adiponectin concentrations: A systematic review and meta-analysis of 43 randomized controlled trial arms.

PubMed

Chruściel, Piotr; Sahebkar, Amirhossein; Rembek-Wieliczko, Magdalena; Serban, Maria-Corina; Ursoniu, Sorin; Mikhailidis, Dimitri P; Jones, Steven R; Mosteoru, Svetlana; Blaha, Michael J; Martin, Seth S; Rysz, Jacek; Toth, Peter P; Lip, Gregory Y H; Pencina, Michael J; Ray, Kausik K; Banach, Maciej

2016-10-01

The effect of statin therapy on plasma adiponectin levels has not been conclusively studied. Therefore, we aimed to evaluate this effect through a systematic review and meta-analysis of available randomized controlled trials (RCTs). Quantitative data synthesis was performed using a random-effects model with weighted mean difference (WMD) and 95% confidence interval (CI) as summary statistics. In 30 studies (43 study arms) with 2953 participants, a significant increase in plasma adiponectin levels was observed after statin therapy (WMD: 0.57 μg/mL, 95% CI: 0.18, 0.95, p = 0.004). In subgroup analysis, atorvastatin, simvastatin, rosuvastatin, pravastatin and pitavastatin were found to change plasma adiponectin concentrations by 0.70 μg/mL (95% CI: -0.26, 1.65), 0.50 μg/mL (95% CI: -0.44, 1.45), -0.70 μg/mL (95% CI: -1.08, -0.33), 0.62 μg/mL (95% CI: -0.12, 1.35), and 0.51 μg/mL (95% CI: 0.30, 0.72), respectively. With respect to duration of treatment, there was a significant increase in the subset of trials lasting ≥12 weeks (WMD: 0.88 μg/mL, 95% CI: 0.19, 1.57, p = 0.012) but not in the subset of <12 weeks of duration (WMD: 0.18 μg/mL, 95% CI: -0.23, 0.58, p = 0.390). Random-effects meta-regression suggested a significant association between statin-induced elevation of plasma adiponectin and changes in plasma low density lipoprotein cholesterol levels (slope: 0.04; 95% CI: 0.01, 0.06; p = 0.002). The meta-analysis showed a significant increase in plasma adiponectin levels following statin therapy. Although statins are known to increase the risk for new onset diabetes mellitus, our data might suggest that the mechanism for this is unlikely to be due to a reduction in adiponectin expression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of sugar-sweetened beverages on plasma acylation stimulating protein, leptin, and adiponectin: Relationships with metabolic outcomes

USDA-ARS?s Scientific Manuscript database

OBJECTIVE: The effects of fructose and glucose consumption on plasma acylation stimulating protein (ASP), adiponectin, and leptin concentrations relative to energy intake, body weight, adiposity, circulating triglycerides, and insulin sensitivity were determined. DESIGN AND METHODS: Thirty two over...

Circulating levels of adiponectin, resistin, and visfatin after mud-bath therapy in patients with bilateral knee osteoarthritis

NASA Astrophysics Data System (ADS)

Fioravanti, Antonella; Giannitti, Chiara; Cheleschi, Sara; Simpatico, Antonella; Pascarelli, Nicola Antonio; Galeazzi, Mauro

2015-11-01

Adipocytokines, including adiponectin, resistin, and visfatin may play an important role in the pathophysiology of osteoarthritis (OA). Spa therapy is one of the most commonly used non-pharmacological approaches for OA, but its mechanisms of action are not completely known. The aim of the present study was to assess whether a cycle of mud-bath therapy (MBT) influences the serum levels of adiponectin, resistin, and visfatin in patients with knee OA. As part of a prospective randomized, single blind-controlled trial evaluating the efficacy of MBT in knee OA, we included in this study 95 outpatients. One group ( n = 49) received a cycle of MBT at the spa center of Chianciano Terme (Italy) in addition to the usual treatment, and one group (control group; n = 46) continued their regular care routine alone. Patients were assessed at basal time and at the end of the study (15 days) for clinical and biochemical parameters. Clinical assessments included spontaneous pain on a visual analog scale (VAS) score and the Western Ontario and McMaster Universities index (WOMAC) subscores for knee OA evaluated as total pain score (W-TPS), total stiffness score (W-TSS), and total physical function score (W-TPFS). Adiponectin, resistin and visfatin serum levels were assessed by enzyme immunoassay methods. At the end of the mud-bath therapy, serum adiponectin levels showed a significant decrease ( p < 0.001), while no significant modifications were found in the control group at day 15. Serum resistin showed a significant decrease ( p < 0.0001) in the MBT group at the end of the study and a significant increase in the control patients ( p < 0.001). No significant modifications of visfatin were found in MBT. Furthermore, we tested the relationships between demographic and clinical parameters and adipocytokine concentrations measured in the MBT group at basal and at the end of the study. In conclusion, the present study shows that a cycle of MBT can modify serum levels of adiponectin and resistin but not the circulating levels of visfatin. In view of the recent evidences about the involvement of adiponectin and resistin in the pathogenesis and progression of OA, the decrease of these adipokines after mud-bath therapy may play a protective role in the course of the disease. However, it remains to be clarified which of the mechanisms of action of MBT may have determined the changes in serum levels of adiponectin and resistin that we observed.

Circulating levels of adiponectin, resistin, and visfatin after mud-bath therapy in patients with bilateral knee osteoarthritis.

PubMed

Fioravanti, Antonella; Giannitti, Chiara; Cheleschi, Sara; Simpatico, Antonella; Pascarelli, Nicola Antonio; Galeazzi, Mauro

2015-11-01

Adipocytokines, including adiponectin, resistin, and visfatin may play an important role in the pathophysiology of osteoarthritis (OA). Spa therapy is one of the most commonly used non-pharmacological approaches for OA, but its mechanisms of action are not completely known. The aim of the present study was to assess whether a cycle of mud-bath therapy (MBT) influences the serum levels of adiponectin, resistin, and visfatin in patients with knee OA. As part of a prospective randomized, single blind-controlled trial evaluating the efficacy of MBT in knee OA, we included in this study 95 outpatients. One group (n = 49) received a cycle of MBT at the spa center of Chianciano Terme (Italy) in addition to the usual treatment, and one group (control group; n = 46) continued their regular care routine alone. Patients were assessed at basal time and at the end of the study (15 days) for clinical and biochemical parameters. Clinical assessments included spontaneous pain on a visual analog scale (VAS) score and the Western Ontario and McMaster Universities index (WOMAC) subscores for knee OA evaluated as total pain score (W-TPS), total stiffness score (W-TSS), and total physical function score (W-TPFS). Adiponectin, resistin and visfatin serum levels were assessed by enzyme immunoassay methods. At the end of the mud-bath therapy, serum adiponectin levels showed a significant decrease (p < 0.001), while no significant modifications were found in the control group at day 15. Serum resistin showed a significant decrease (p < 0.0001) in the MBT group at the end of the study and a significant increase in the control patients (p < 0.001). No significant modifications of visfatin were found in MBT. Furthermore, we tested the relationships between demographic and clinical parameters and adipocytokine concentrations measured in the MBT group at basal and at the end of the study. In conclusion, the present study shows that a cycle of MBT can modify serum levels of adiponectin and resistin but not the circulating levels of visfatin. In view of the recent evidences about the involvement of adiponectin and resistin in the pathogenesis and progression of OA, the decrease of these adipokines after mud-bath therapy may play a protective role in the course of the disease. However, it remains to be clarified which of the mechanisms of action of MBT may have determined the changes in serum levels of adiponectin and resistin that we observed.

Differential Susceptibility of Germ and Leydig Cells to Cadmium-Mediated Toxicity: Impact on Testis Structure, Adiponectin Levels, and Steroidogenesis

PubMed Central

Cupertino, Marli C.; Neves, Ana C.; Oliveira, Juraci A.

2017-01-01

This study investigated the relationship between germ and Leydig cell death, testosterone, and adiponectin levels in cadmium-mediated acute toxicity. Cadmium chloride was administered in a single dose to five groups of rats: G1 (0.9% NaCl) and G2 to G5 (0.67, 0.74, 0.86, and 1.1 mg Cd/kg). After 7 days, the animals were euthanized, and the testosterone and testes were analyzed. Dose-dependent Cd accumulation in the testes was identified. At 0.86 and 1.1 mg/kg, animals exhibited marked inflammatory infiltrate and disorganization of the seminiferous epithelium. While Leydig cells were morphologically resistant to Cd toxicity, massive germ cell death and DNA oxidation and fragmentation were observed. Although numerical density of Leydig cells was unchanged, testosterone levels were significantly impaired in animals exposed to 0.86 and 1.1 mg Cd/kg, occurring in parallel with the reduction in total adiponectins and the increase in high-molecular weight adiponectin levels. Our findings indicated that Leydig and germ cells exhibit differential microstructural resistance to Cd toxicity. While germ cells are a primary target of Cd-induced toxicity, Leydig cells remain resistant to death even when exposed to high doses of Cd. Despite morphological resistance, steroidogenesis was drastically impaired by Cd exposure, an event potentially related to the imbalance in adiponectin production. PMID:29422988

The Effect of Vegan Protein-Based Diets on Metabolic Parameters, Expressions of Adiponectin and Its Receptors in Wistar Rats

PubMed Central

Chen, Jie-Hua; Song, Jia; Chen, Yan; Ding, Qiang; Peng, Anfang; Mao, Limei

2016-01-01

Vegan protein-based diet has attracted increasing interest in the prevention of metabolic syndrome (MetS). Meanwhile, adiponectin has become a highly potential molecular target in the prevention of MetS. Our study will identify a potential vegan protein diet for the prevention of MetS using rat models. Thirty-six Wistar rats were randomly assigned into three groups and given diets containing one of the following proteins for 12 weeks: casein (CAS, control diet), soy protein (SOY), and gluten-soy mixed protein (GSM). Changes in metabolic parameters as well as the expressions of adiponectin and its receptors were identified. Compared to CAS diet, both SOY and GSM diets led to decreases in blood total cholesterol and triglycerides, but only GSM diet led to an increase in HDL-cholesterol; no marked difference was observed in blood glucose in all three groups; HOMA-IR was found lower only in SOY group. Among groups, the order of serum adiponectin level was found as GSM > SOY > CAS. Similar order pattern was also observed in expression of adiponectin in adipose tissue and AdipoR1 mRNA in skeletal muscle. Our results suggested for the first time that, besides SOY diet, GSM diet could also be a possible substitute of animal protein to prevent MetS. PMID:27763537

Adiponectin, interleukin-6, monocyte chemoattractant protein-1, and regional fat mass during 12-month randomized treatment with metformin and/or oral contraceptives in polycystic ovary syndrome.

PubMed

Glintborg, Dorte; Mumm, Hanne; Altinok, Magda Lambaa; Richelsen, Bjørn; Bruun, Jens Meldgaard; Andersen, Marianne

2014-08-01

Central obesity in polycystic ovary syndrome (PCOS) is associated with increased inflammatory markers and increased risk for type 2 diabetes. To evaluate if improved body composition during treatment with metformin (M) vs. oral contraceptive pills (OCP) was associated with changes in circulating adiponectin, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1. Ninety patients with PCOS were randomized to 12-month treatment with M (2 g/day), M + OCP (150 mg desogestrel + 30 microgram ethinylestradiol) or OCP. Adiponectin, IL-6, MCP-1, whole body DXA scans, and clinical evaluations were performed before and after the intervention period in the 65 study completers. Changes in inflammatory markers and changes in total and regional fat mass estimates. Adiponectin, IL-6, and MCP-1 levels were unchanged during the three types of medical intervention. Treatment with M and M + OCP was superior to OCP regarding decreased regional fat mass. Baseline adiponectin and IL-6 were associated with BMI, waist, and trunk fat mass. Changes in trunk fat were significantly associated with changes in IL-6 and MCP-1 during M + OCP. Long-term treatment with M alone or in combination with OCP was associated with improved body composition compared to OCP, whereas inflammatory markers were unchanged. OCP was not associated with increased inflammatory markers despite a small but significant weight gain.

Relationship between adiponectin levels, acylated ghrelin levels, and short-term body mass index changes in children with diabetes mellitus type 1 at diagnosis and after insulin therapy.

PubMed

Martos-Moreno, Gabriel A; Barrios, Vicente; Soriano-Guillén, Leandro; Argente, Jesús

2006-11-01

To determine the effect of the initial metabolic imbalance and its restoration after insulin therapy on adiponectin and acylated ghrelin levels in children with type 1 diabetes mellitus (T1DM). Twenty prepubertal children with newly diagnosed T1DM were prospectively studied at diagnosis and after 1 and 4 months of therapy. Body mass index (BMI) and serum levels of adiponectin, resistin, total and acylated ghrelin, leptin, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) were determined. The control group comprised 40 healthy prepubertal children. BMI was decreased at diagnosis, normalized at 1 month, and remained so thereafter. Adiponectin levels at diagnosis were similar to controls, increasing significantly after 1 month and normalizing at 4 months. Acylated ghrelin levels were lower at diagnosis, with a significant increase at 1 month and normalizing at 4 months. Resistin levels were normal at all time points. Leptin levels were decreased, while TNF-alpha and IL-6 were increased at diagnosis and normalized at 1 month. These findings suggest that BMI is not the main predictor of acylated ghrelin or adiponectin levels in newly diagnosed T1DM subjects and that these peptides may play an important role in the metabolic adaptation in this disease.

Paracrine-acting adiponectin promotes mammary epithelial differentiation and synergizes with genistein to enhance transcriptional response to estrogen receptor beta signaling

USDA-ARS?s Scientific Manuscript database

Mammary stromal adipocytes constitute an active site for the synthesis of the adipokine adiponectin (APN) that may influence the mammary epithelial microenvironment. The relationship between 'local', mammary tissue-derived APN and breast cancer risk is poorly understood. Herein, we identify a novel ...

Adiponectin and the mediation of HDL cholesterol change with improved lifestyle: The Look AHEAD Study

USDA-ARS?s Scientific Manuscript database

Adipose tissue dysfunction plays a key role in the development of the metabolic abnormalities characteristic of type 2 diabetes (T2DM) and participates actively in lipid metabolism. Adiponectin, found abundantly in circulation and a marker of adipose health, is decreased in obese persons with T2DM. ...

Cardioprotective Effect of Intermittent Fasting is Associated with an Elevation of Adiponectin Levels in Rats

PubMed Central

Wan, Ruiqian; Ahmet, Ismayil; Brown, Martin; Cheng, Aiwu; Kamimura, Naomi; Talan, Mark; Mattson, Mark P.

2009-01-01

It has been reported that dietary energy restriction, including intermittent fasting (IF), can protect heart and brain cells against injury and improve functional outcome in animal models of myocardial infarction and stroke. Here we report that IF improves glycemic control and protects the myocardium against ischemia-induced cell damage and inflammation in rats. Echocardiographic analysis of heart structural and functional variables revealed that IF attenuates the growth-related increase in posterior ventricular wall thickness, , end systolic and diastolic volumes, and reduces the ejection fraction. The size of the ischemic infarct 24 hours following permanent ligation of a coronary artery was significantly smaller, and markers of inflammation (infiltration of leukocytes in the area at risk and plasma IL-6 levels) were less, in IF rats compared to rats on the control diet. IF resulted in increased levels of circulating adiponectin prior to and after myocardial infarction. Because recent studies have shown that adiponectin can protect the heart against ischemic injury, our findings suggest a potential role for adiponectin as a mediator of the cardioprotective effect of IF. PMID:19423320

Aged Garlic Extract Improves Adiponectin Levels in Subjects with Metabolic Syndrome: A Double-Blind, Placebo-Controlled, Randomized, Crossover Study

PubMed Central

Gómez-Arbeláez, Diego; Lahera, Vicente; Oubiña, Pilar; Valero-Muñoz, Maria; de las Heras, Natalia; Rodríguez, Yudy; García, Ronald Gerardo; Camacho, Paul Anthony; López-Jaramillo, Patricio

2013-01-01

Background. Garlic (Allium sativum) has been shown to have important benefits in individuals at high cardiovascular risk. The aim of the present study was to evaluate the effects of the administration of aged garlic extract (AGE) on the risk factors that constitute the cluster of metabolic syndrome (MS). Methods and Design. Double-blind, crossover, randomized, placebo-controlled clinical trial to assess the effect of 1.2 g/day of AGE (Kyolic), for 24 weeks of treatment (12 weeks of AGE and 12 weeks of placebo), on subjects with MS. Results. The administration of AGE increased the plasma levels of adiponectin (P = 0.027). No serious side effects associated with the intervention were reported. Conclusion. The present results have shown for the first time that the administration of AGE for 12 weeks increased plasma adiponectin levels in patients with MS. This suggests that AGE might be a useful, novel, nonpharmacological therapeutic intervention to increase adiponectin and to prevent cardiovascular (CV) complications in individuals with MS. PMID:23533302

Ubiquitin specific protease 2 acts as a key modulator for the regulation of cell cycle by adiponectin and leptin in cancer cells.

PubMed

Nepal, Saroj; Shrestha, Anup; Park, Pil-Hoon

2015-09-05

Adiponectin and leptin, both produced from adipose tissue, cause cell cycle arrest and progression, respectively in cancer cells. Ubiquitin specific protease-2 (USP-2), a deubiquitinating enzyme, is known to impair proteasome-induced degradation of cyclin D1, a critical cell cycle regulator. Herein, we investigated the effects of these adipokines on USP-2 expression and its potential role in the modulation of cell cycle. Treatment with globular adiponectin (gAcrp) decreased, whereas leptin increased USP-2 expression both in human hepatoma and breast cancer cells. In addition, overexpression or gene silencing of USP-2 affected cyclin D1 expression and cell cycle progression/arrest by adipokines. Adiponectin and leptin also modulated in vitro proteasomal activity, which was partially dependent on USP-2 expression. Taken together, our results reveal that modulation of USP-2 expression plays a crucial role in cell cycle regulation by adipokines. Thus, USP-2 would be a promising therapeutic target for the modulation of cancer cell growth by adipokines. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Sarah; Jung, Jaesung; Kim, Taeyeung

In this study, HepG2-hepatitis B virus (HBV)-stable cells that did not overexpress HBx and HBx-deficient mutant-transfected cells were analyzed for their expression of HBV-induced, upregulated adipogenic and lipogenic genes. The mRNAs of CCAAT enhancer binding protein {alpha} (C/EBP{alpha}), peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), adiponectin, liver X receptor {alpha} (LXR{alpha}), sterol regulatory element binding protein 1c (SREBP1c), and fatty acid synthase (FAS) were expressed at higher levels in HepG2-HBV and lamivudine-treated stable cells and HBx-deficient mutant-transfected cells than in the HepG2 cells. Lamivudine treatment reduced the mRNA levels of PPAR{gamma} and C/EBP{alpha}. Conversely, HBV replication was upregulated by adiponectin and PPAR{gamma}more » agonist rosiglitazone treatments and was downregulated by adiponectin siRNAs. Collectively, our results demonstrate that HBV replication and/or protein expression, even in the absence of HBx, upregulated adipogenic or lipogenic genes, and that the control of adiponectin might prove useful as a therapeutic modality for the treatment of chronic hepatitis B.« less

The role of adiponectin and adipolin as anti-inflammatory adipokines in the formation of macrophage foam cells and their association with cardiovascular diseases.

PubMed

Sargolzaei, Javad; Chamani, Elham; Kazemi, Tooba; Fallah, Soudabeh; Soori, Hosna

2018-04-01

Obesity is one of the major public health concerns that is closely associated with obesity-related disorders such as type 2 diabetes mellitus (T2DM), hypertension, and atherosclerosis. Atherosclerosis is a chronic disease characterized by excess cholesterol deposition in the arterial intima and the formation of foam cells. Adipocytokines or adipokines are secreted by the adipose tissue as endocrine glands; adiponectin and adipolin are among these adipokines that are associated with obese and insulin-resistant phenotypes. Adipolin and adiponectin are cytokines that exert substantial impact on obesity, progression of atherosclerosis, insulin resistance, and glucose metabolism. In this paper, we review the formation of macrophage foam cells, which are associated with atherosclerosis, and the macrophage mechanism, which includes uptake, esterification, and release. We also summarize current information on adipose tissue-derived hormone and energy homeostasis in obesity. Finally, the role of adipokines, e.g., adipoline and adiponectin, in regulating metabolic, cardiovascular diseases is discussed. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

The opposite effect of isotype-selective monoamine oxidase inhibitors on adipogenesis in human bone marrow mesenchymal stem cells.

PubMed

Byun, Youngjoo; Park, Jongho; Hong, Soo Hyun; Han, Mi Hwa; Park, Suzie; Jung, Hyo-Il; Noh, Minsoo

2013-06-01

Adiponectin production during adipocyte differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) can be used to evaluate the pharmacological activity of anti-diabetic drugs to improve insulin sensitivity. Monoamine oxidase (MAO) inhibitors such as phenelzine and pargyline inhibit adipogenesis in murine pre-adipocytes. In this study, however, we found that selective MAO-A inhibitors, moclobemide and Ro41-1049, and a selective MAO-B inhibitor, selegiline, promoted adiponectin production during adipocyte differentiation in hBM-MSCs, which suggested the anti-diabetic potential of these drugs. In contrast, non-selective MAO inhibitors, phenelzine and tranylcypromine, inhibited adipocyte differentiation of hBM-MSCs. Concomitant treatments of MAO-A and MAO-B selective inhibitors did not change the stimulatory effect on adiponectin production in hBM-MSCs. Taken together, the opposite effects of isotype-selective MAO inhibitors on adiponectin production during adipogenesis in hBM-MSCs may not be directly associated with the inhibitory effects of MAO, suggested that the structure of MAO inhibitors may contain a novel anti-diabetic pharmacophore. Copyright © 2013 Elsevier Ltd. All rights reserved.

Exercise Training Modifies Ghrelin and Adiponectin Concentrations and Is Related to Inflammation in Older Adults

PubMed Central

Carrillo, Andres E.; Timmerman, Kyle L.; Jennings, Kristofer; Coen, Paul M.; Pence, Brandt D.; Flynn, Michael G.

2014-01-01

The purpose of this study was to observe exercise training–induced effects on adiponectin, leptin, and ghrelin. Twenty-nine older, healthy participants were classified as physically active (comparison group: N = 15, 70.9±1.2 years) or physically inactive (exercise group: N = 14, 70.5±1.4 years). Exercise group participants completed 12 weeks of combined aerobic and resistance exercise training, whereas comparison group participants maintained their current level of exercise and served as a physically active comparison group. Monocyte phenotype, as well as serum ghrelin, leptin, adiponectin, and soluble tumor necrosis factor receptor II were analyzed prior to and following the 12-week period. Ghrelin and adiponectin increased 47% and 55%, respectively, in exercise group participants following exercise training. Percent change in ghrelin (post and pre) was negatively correlated with the percent change in CD14+CD16+ monocytes (post and pre) in exercise group participants. Despite no changes in body mass, these data contribute to evidence for the anti-inflammatory effects of exercise. PMID:24013674

Osmotin: a plant sentinel and a possible agonist of mammalian adiponectin

PubMed Central

Anil Kumar, S.; Hima Kumari, P.; Shravan Kumar, G.; Mohanalatha, C.; Kavi Kishor, P. B.

2015-01-01

Osmotin is a stress responsive antifungal protein belonging to the pathogenesis-related (PR)-5 family that confers tolerance to both biotic and abiotic stresses in plants. Protective efforts of osmotin in plants range from high temperature to cold and salt to drought. It lyses the plasma membrane of the pathogens. It is widely distributed in fruits and vegetables. It is a differentially expressed and developmentally regulated protein that protects the cells from osmotic stress and invading pathogens as well, by structural or metabolic alterations. During stress conditions, osmotin helps in the accumulation of the osmolyte proline, which quenches reactive oxygen species and free radicals. Osmotin expression results in the accumulation of storage reserves and increases the shelf-life of fruits. It binds to a seven-transmembrane-domain receptor-like protein and induces programmed cell death in Saccharomyces cerevisiae through RAS2/cAMP signaling pathway. Adiponectin, produced in adipose tissues of mammals, is an insulin-sensitizing hormone. Strangely, osmotin acts like the mammalian hormone adiponectin in various in vitro and in vivo models. Adiponectin and osmotin, the two receptor binding proteins do not share sequence similarity at the amino acid level, but interestingly they have a similar structural and functional properties. In experimental mice, adiponectin inhibits endothelial cell proliferation and migration, primary tumor growth, and reduces atherosclerosis. This retrospective work examines the vital role of osmotin in plant defense and as a potential targeted therapeutic drug for humans. PMID:25852715

Osmotin: a plant sentinel and a possible agonist of mammalian adiponectin.

PubMed

Anil Kumar, S; Hima Kumari, P; Shravan Kumar, G; Mohanalatha, C; Kavi Kishor, P B

2015-01-01

Osmotin is a stress responsive antifungal protein belonging to the pathogenesis-related (PR)-5 family that confers tolerance to both biotic and abiotic stresses in plants. Protective efforts of osmotin in plants range from high temperature to cold and salt to drought. It lyses the plasma membrane of the pathogens. It is widely distributed in fruits and vegetables. It is a differentially expressed and developmentally regulated protein that protects the cells from osmotic stress and invading pathogens as well, by structural or metabolic alterations. During stress conditions, osmotin helps in the accumulation of the osmolyte proline, which quenches reactive oxygen species and free radicals. Osmotin expression results in the accumulation of storage reserves and increases the shelf-life of fruits. It binds to a seven-transmembrane-domain receptor-like protein and induces programmed cell death in Saccharomyces cerevisiae through RAS2/cAMP signaling pathway. Adiponectin, produced in adipose tissues of mammals, is an insulin-sensitizing hormone. Strangely, osmotin acts like the mammalian hormone adiponectin in various in vitro and in vivo models. Adiponectin and osmotin, the two receptor binding proteins do not share sequence similarity at the amino acid level, but interestingly they have a similar structural and functional properties. In experimental mice, adiponectin inhibits endothelial cell proliferation and migration, primary tumor growth, and reduces atherosclerosis. This retrospective work examines the vital role of osmotin in plant defense and as a potential targeted therapeutic drug for humans.

Measurement of salivary resistin, visfatin and adiponectin levels.

PubMed

Mamali, Irene; Roupas, Nikolaos D; Armeni, Anastasia K; Theodoropoulou, Anastasia; Markou, Kostas B; Georgopoulos, Neoklis A

2012-01-01

Hormonal determination in saliva offers several advantages. Peptides enter the salivary glands either by active transport mechanisms or are expressed and secreted by the salivary glands themselves. The collection of saliva is a noninvasive, easily repeatable and less stressful technique than blood withdrawal. The purpose of the present study was to introduce a method for measuring salivary resistin, visfatin and adiponectin levels and to evaluate their associations with serum levels. Resistin, visfatin and adiponectin levels were measured in serum and saliva of 50 healthy adult volunteers (17 male and 33 female) using commercial enzyme immunoassay kits for serum with minor modifications. The present study documented the determination of resistin and adiponectin levels in saliva and the significant correlation of salivary levels with serum levels (r=0.441, p<0.01 and r=0.347, p<0.05, respectively). Moreover, the identification of visfatin in saliva was achieved, but no significant correlation with serum visfatin levels was observed. To our knowledge, this is the first study to report the determination of resistin and visfatin in saliva and the significant correlation of salivary resistin with serum levels, while it confirmed the significant association between salivary and serum adiponectin. The introduction of salivary determinations of adipokines could contribute to the elucidation of the physiology and the role of the specific adipokines in various clinical conditions (obesity, insulin resistance, inflammation, reproduction, energy imbalance and stress response). Copyright © 2011 Elsevier Inc. All rights reserved.

Association of subcutaneous and visceral fat mass with serum concentrations of adipokines in subjects with type 2 diabetes mellitus.

PubMed

Saito, Tomoyuki; Murata, Miho; Otani, Taeko; Tamemoto, Hiroyuki; Kawakami, Masanobu; Ishikawa, San-E

2012-01-01

The goal of the study was to examine the association of subcutaneous and visceral fat mass with serum concentrations of adipokines in 130 subjects with type 2 diabetes mellitus. The levels of serum high sensitivity C-reactive protein (HS-CRP), adiponectin, high-molecular-weight (HMW) adiponectin, interleukin-18, and retinol-binding protein 4 were measured. Percentage body fat was determined by dual energy X-ray absorptiometry, and subcutaneous and visceral fat areas were measured by abdominal CT. HS-CRP had significant positive correlations with percentage body fat and subcutaneous fat area, and a particularly significant positive correlation with visceral fat area. Serum adiponectin had a negative correlation with the subcutaneous and visceral fat areas, with the strongest correlation with the visceral fat area. Similar results were obtained for HMW adiponectin. Serum adiponectin had a negative correlation with visceral fat area in subjects with a visceral fat area < 100 cm², but not in those with a visceral fat area ≥ 100 cm². In contrast, serum HS-CRP showed a positive correlation with visceral fat area in subjects with visceral fat area ≥ 100 cm², but not in those with a visceral fat area < 100 cm². These findings indicate that an increased visceral fat area is associated with inflammatory changes, and that inflammatory reactions may alter the functional properties of visceral fat in type 2 diabetes mellitus.

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

PubMed

Dastani, Zari; Hivert, Marie-France; Timpson, Nicholas; Perry, John R B; Yuan, Xin; Scott, Robert A; Henneman, Peter; Heid, Iris M; Kizer, Jorge R; Lyytikäinen, Leo-Pekka; Fuchsberger, Christian; Tanaka, Toshiko; Morris, Andrew P; Small, Kerrin; Isaacs, Aaron; Beekman, Marian; Coassin, Stefan; Lohman, Kurt; Qi, Lu; Kanoni, Stavroula; Pankow, James S; Uh, Hae-Won; Wu, Ying; Bidulescu, Aurelian; Rasmussen-Torvik, Laura J; Greenwood, Celia M T; Ladouceur, Martin; Grimsby, Jonna; Manning, Alisa K; Liu, Ching-Ti; Kooner, Jaspal; Mooser, Vincent E; Vollenweider, Peter; Kapur, Karen A; Chambers, John; Wareham, Nicholas J; Langenberg, Claudia; Frants, Rune; Willems-Vandijk, Ko; Oostra, Ben A; Willems, Sara M; Lamina, Claudia; Winkler, Thomas W; Psaty, Bruce M; Tracy, Russell P; Brody, Jennifer; Chen, Ida; Viikari, Jorma; Kähönen, Mika; Pramstaller, Peter P; Evans, David M; St Pourcain, Beate; Sattar, Naveed; Wood, Andrew R; Bandinelli, Stefania; Carlson, Olga D; Egan, Josephine M; Böhringer, Stefan; van Heemst, Diana; Kedenko, Lyudmyla; Kristiansson, Kati; Nuotio, Marja-Liisa; Loo, Britt-Marie; Harris, Tamara; Garcia, Melissa; Kanaya, Alka; Haun, Margot; Klopp, Norman; Wichmann, H-Erich; Deloukas, Panos; Katsareli, Efi; Couper, David J; Duncan, Bruce B; Kloppenburg, Margreet; Adair, Linda S; Borja, Judith B; Wilson, James G; Musani, Solomon; Guo, Xiuqing; Johnson, Toby; Semple, Robert; Teslovich, Tanya M; Allison, Matthew A; Redline, Susan; Buxbaum, Sarah G; Mohlke, Karen L; Meulenbelt, Ingrid; Ballantyne, Christie M; Dedoussis, George V; Hu, Frank B; Liu, Yongmei; Paulweber, Bernhard; Spector, Timothy D; Slagboom, P Eline; Ferrucci, Luigi; Jula, Antti; Perola, Markus; Raitakari, Olli; Florez, Jose C; Salomaa, Veikko; Eriksson, Johan G; Frayling, Timothy M; Hicks, Andrew A; Lehtimäki, Terho; Smith, George Davey; Siscovick, David S; Kronenberg, Florian; van Duijn, Cornelia; Loos, Ruth J F; Waterworth, Dawn M; Meigs, James B; Dupuis, Josee; Richards, J Brent; Voight, Benjamin F; Scott, Laura J; Steinthorsdottir, Valgerdur; Dina, Christian; Welch, Ryan P; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S; Thorleifsson, Gudmar; McCulloch, Laura J; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming; Willer, Cristen J; Raychaudhuri, Soumya; McCarroll, Steve A; Hofmann, Oliver M; Segrè, Ayellet V; van Hoek, Mandy; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Benediktsson, Rafn; Bennett, Amanda J; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori L; Boström, Kristina Bengtsson; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noël P; Charpentier, Guillaume; Chines, Peter S; Cornelis, Marilyn; Crawford, Gabe; Doney, Alex S F; Elliott, Katherine S; Elliott, Amanda L; Erdos, Michael R; Fox, Caroline S; Franklin, Christopher S; Ganser, Martha; Gieger, Christian; Grarup, Niels; Green, Todd; Griffin, Simon; Groves, Christopher J; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U; Johnson, Paul R V; Jørgensen, Torben; Kao, Wen H L; Kong, Augustine; Kraft, Peter; Kuusisto, Johanna; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Payne, Felicity; Petersen, Ann-Kristin; Platou, Carl; Proença, Christine; Prokopenko, Inga; Rathmann, Wolfgang; Rayner, N William; Robertson, Neil R; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J; Saxena, Richa; Shields, Beverley M; Shrader, Peter; Sigurdsson, Gunnar; Sparsø, Thomas; Strassburger, Klaus; Stringham, Heather M; Sun, Qi; Swift, Amy J; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; van Dam, Rob M; van Haeften, Timon W; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V; Walters, G Bragi; Weedon, Michael N; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N; Cauchi, Stephane; Collins, Francis S; Gloyn, Anna L; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A; Hitman, Graham A; Hofman, Albert; Hunter, David J; Hveem, Kristian; Laakso, Markku; Morris, Andrew D; Palmer, Colin N A; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D; Tuomilehto, Jaakko; Uitterlinden, Andre; Walker, Mark; Watanabe, Richard M; Abecasis, Goncalo R; Boehm, Bernhard O; Campbell, Harry; Daly, Mark J; Hattersley, Andrew T; Pedersen, Oluf; Barroso, Inês; Groop, Leif; Sladek, Rob; Thorsteinsdottir, Unnur; Wilson, James F; Illig, Thomas; Froguel, Philippe; van Duijn, Cornelia M; Stefansson, Kari; Altshuler, David; Boehnke, Michael; McCarthy, Mark I; Soranzo, Nicole; Wheeler, Eleanor; Glazer, Nicole L; Bouatia-Naji, Nabila; Mägi, Reedik; Randall, Joshua; Elliott, Paul; Rybin, Denis; Dehghan, Abbas; Hottenga, Jouke Jan; Song, Kijoung; Goel, Anuj; Lajunen, Taina; Doney, Alex; Cavalcanti-Proença, Christine; Kumari, Meena; Timpson, Nicholas J; Zabena, Carina; Ingelsson, Erik; An, Ping; O'Connell, Jeffrey; Luan, Jian'an; Elliott, Amanda; McCarroll, Steven A; Roccasecca, Rosa Maria; Pattou, François; Sethupathy, Praveen; Ariyurek, Yavuz; Barter, Philip; Beilby, John P; Ben-Shlomo, Yoav; Bergmann, Sven; Bochud, Murielle; Bonnefond, Amélie; Borch-Johnsen, Knut; Böttcher, Yvonne; Brunner, Eric; Bumpstead, Suzannah J; Chen, Yii-Der Ida; Chines, Peter; Clarke, Robert; Coin, Lachlan J M; Cooper, Matthew N; Crisponi, Laura; Day, Ian N M; de Geus, Eco J C; Delplanque, Jerome; Fedson, Annette C; Fischer-Rosinsky, Antje; Forouhi, Nita G; Franzosi, Maria Grazia; Galan, Pilar; Goodarzi, Mark O; Graessler, Jürgen; Grundy, Scott; Gwilliam, Rhian; Hallmans, Göran; Hammond, Naomi; Han, Xijing; Hartikainen, Anna-Liisa; Hayward, Caroline; Heath, Simon C; Hercberg, Serge; Hillman, David R; Hingorani, Aroon D; Hui, Jennie; Hung, Joe; Kaakinen, Marika; Kaprio, Jaakko; Kesaniemi, Y Antero; Kivimaki, Mika; Knight, Beatrice; Koskinen, Seppo; Kovacs, Peter; Kyvik, Kirsten Ohm; Lathrop, G Mark; Lawlor, Debbie A; Le Bacquer, Olivier; Lecoeur, Cécile; Li, Yun; Mahley, Robert; Mangino, Massimo; Martínez-Larrad, María Teresa; McAteer, Jarred B; McPherson, Ruth; Meisinger, Christa; Melzer, David; Meyre, David; Mitchell, Braxton D; Mukherjee, Sutapa; Naitza, Silvia; Neville, Matthew J; Orrù, Marco; Pakyz, Ruth; Paolisso, Giuseppe; Pattaro, Cristian; Pearson, Daniel; Peden, John F; Pedersen, Nancy L; Pfeiffer, Andreas F H; Pichler, Irene; Polasek, Ozren; Posthuma, Danielle; Potter, Simon C; Pouta, Anneli; Province, Michael A; Rayner, Nigel W; Rice, Kenneth; Ripatti, Samuli; Rivadeneira, Fernando; Rolandsson, Olov; Sandbaek, Annelli; Sandhu, Manjinder; Sanna, Serena; Sayer, Avan Aihie; Scheet, Paul; Seedorf, Udo; Sharp, Stephen J; Shields, Beverley; Sigurðsson, Gunnar; Sijbrands, Eric J G; Silveira, Angela; Simpson, Laila; Singleton, Andrew; Smith, Nicholas L; Sovio, Ulla; Swift, Amy; Syddall, Holly; Syvänen, Ann-Christine; Tönjes, Anke; Uitterlinden, André G; van Dijk, Ko Willems; Varma, Dhiraj; Visvikis-Siest, Sophie; Vitart, Veronique; Vogelzangs, Nicole; Waeber, Gérard; Wagner, Peter J; Walley, Andrew; Ward, Kim L; Watkins, Hugh; Wild, Sarah H; Willemsen, Gonneke; Witteman, Jaqueline C M; Yarnell, John W G; Zelenika, Diana; Zethelius, Björn; Zhai, Guangju; Zhao, Jing Hua; Zillikens, M Carola; Borecki, Ingrid B; Meneton, Pierre; Magnusson, Patrik K E; Nathan, David M; Williams, Gordon H; Silander, Kaisa; Bornstein, Stefan R; Schwarz, Peter; Spranger, Joachim; Karpe, Fredrik; Shuldiner, Alan R; Cooper, Cyrus; Serrano-Ríos, Manuel; Lind, Lars; Palmer, Lyle J; Hu, Frank B; Franks, Paul W; Ebrahim, Shah; Marmot, Michael; Kao, W H Linda; Pramstaller, Peter Paul; Wright, Alan F; Stumvoll, Michael; Hamsten, Anders; Buchanan, Thomas A; Valle, Timo T; Rotter, Jerome I; Penninx, Brenda W J H; Boomsma, Dorret I; Cao, Antonio; Scuteri, Angelo; Schlessinger, David; Uda, Manuela; Ruokonen, Aimo; Jarvelin, Marjo-Riitta; Peltonen, Leena; Mooser, Vincent; Sladek, Robert; Musunuru, Kiran; Smith, Albert V; Edmondson, Andrew C; Stylianou, Ioannis M; Koseki, Masahiro; Pirruccello, James P; Chasman, Daniel I; Johansen, Christopher T; Fouchier, Sigrid W; Peloso, Gina M; Barbalic, Maja; Ricketts, Sally L; Bis, Joshua C; Feitosa, Mary F; Orho-Melander, Marju; Melander, Olle; Li, Xiaohui; Li, Mingyao; Cho, Yoon Shin; Go, Min Jin; Kim, Young Jin; Lee, Jong-Young; Park, Taesung; Kim, Kyunga; Sim, Xueling; Ong, Rick Twee-Hee; Croteau-Chonka, Damien C; Lange, Leslie A; Smith, Joshua D; Ziegler, Andreas; Zhang, Weihua; Zee, Robert Y L; Whitfield, John B; Thompson, John R; Surakka, Ida; Spector, Tim D; Smit, Johannes H; Sinisalo, Juha; Scott, James; Saharinen, Juha; Sabatti, Chiara; Rose, Lynda M; Roberts, Robert; Rieder, Mark; Parker, Alex N; Pare, Guillaume; O'Donnell, Christopher J; Nieminen, Markku S; Nickerson, Deborah A; Montgomery, Grant W; McArdle, Wendy; Masson, David; Martin, Nicholas G; Marroni, Fabio; Lucas, Gavin; Luben, Robert; Lokki, Marja-Liisa; Lettre, Guillaume; Launer, Lenore J; Lakatta, Edward G; Laaksonen, Reijo; Kyvik, Kirsten O; König, Inke R; Khaw, Kay-Tee; Kaplan, Lee M; Johansson, Åsa; Janssens, A Cecile J W; Igl, Wilmar; Hovingh, G Kees; Hengstenberg, Christian; Havulinna, Aki S; Hastie, Nicholas D; Harris, Tamara B; Haritunians, Talin; Hall, Alistair S; Groop, Leif C; Gonzalez, Elena; Freimer, Nelson B; Erdmann, Jeanette; Ejebe, Kenechi G; Döring, Angela; Dominiczak, Anna F; Demissie, Serkalem; Deloukas, Panagiotis; de Faire, Ulf; Crawford, Gabriel; Chen, Yii-der I; Caulfield, Mark J; Boekholdt, S Matthijs; Assimes, Themistocles L; Quertermous, Thomas; Seielstad, Mark; Wong, Tien Y; Tai, E-Shyong; Feranil, Alan B; Kuzawa, Christopher W; Taylor, Herman A; Gabriel, Stacey B; Holm, Hilma; Gudnason, Vilmundur; Krauss, Ronald M; Ordovas, Jose M; Munroe, Patricia B; Kooner, Jaspal S; Tall, Alan R; Hegele, Robert A; Kastelein, John J P; Schadt, Eric E; Strachan, David P; Reilly, Muredach P; Samani, Nilesh J; Schunkert, Heribert; Cupples, L Adrienne; Sandhu, Manjinder S; Ridker, Paul M; Rader, Daniel J; Kathiresan, Sekar

2012-01-01

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Association of adiponectin/leptin ratio with carbohydrate and lipid metabolism parameters in HIV-infected patients during antiretroviral therapy.

PubMed

Tiliscan, Catalin; Arama, Victoria; Mihailescu, Raluca; Munteanu, Daniela; Iacob, Diana Gabriela; Popescu, Cristina; Catana, Remulus; Negru, Anca; Lobodan, Alina; Arama, Stefan Sorin

2018-02-16

Adiponectin and leptin are adipose tissue hormones that regulate important lipid and glucose metabolic pathways. Our objective was to evaluate the interplay of these hormones described by the adiponectin/leptin ratio (ALR) in correlation to lipid and carbohydrate metabolism parameters in nondiabetic HIV-infected patients during antiretroviral therapy (ART). We enrolled consecutive nondiabetic patients with confirmed HIV infection, undergoing stable ART regimens for at least six months. Blood samples were collected and tested for immunological and virological parameters, adiponectin and leptin, fasting insulin, fasting plasma glucose, fasting triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol. ALR was computed for each patient. Resistance to insulin was assessed by calculating the Quantitative Insulin Sensitivity Check Index (QUICKI). We enrolled 87 HIV-infected persons, with a mean age of 31.7 years (range: 18-65), including 47 men (mean age = 32.8 years) and 40 women (mean age = 30.5 years). The median value of ALR was 6.8 (interquartile range - IQR = 17.1). In male patients, ALR was inversely associated with the serum level of triglycerides (R = 0.285, p = 0.05), total cholesterol (R = 0.326, p = 0.02), and LDL cholesterol (R = 0.298, p = 0.04). Also for the male cohort, an increase in ALR seemed to improve insulin sensitivity (R = 0.323, p = 0.02) and serum HDL cholesterol (R = 0.597, p = 0.01). None of these correlations were observed in HIV-infected women. Adiponectin and leptin seem to play important but different gender-specific roles in the pathogenesis of lipid and glucose metabolism of HIV-infected patients undergoing antiretroviral therapy. ALR, adiponectin/leptin ratio; BMI, body mass index; LDL, low-density lipoprotein; HDL, high-density lipoprotein; QUICKI, Quantitative Insulin Sensitivity Check Index.

Chlorogenic Acid Improves Late Diabetes through Adiponectin Receptor Signaling Pathways in db/db Mice

PubMed Central

Jin, Shasha; Chang, Cuiqing; Zhang, Lantao; Liu, Yang; Huang, Xianren; Chen, Zhimin

2015-01-01

The aim of this study was to examine the effects of chlorogenic acid (CGA) on glucose and lipid metabolism in late diabetic db/db mice, as well as on adiponectin receptors and their signaling molecules, to provide evidence for CGA in the prevention of type 2 diabetes. We randomly divided 16 female db/db mice into db/db-CGA and db/db-control (CON) groups equally; db/m mice were used as control mice. The mice in both the db/db-CGA and db/m-CGA groups were administered 80 mg/kg/d CGA by lavage for 12 weeks, whereas the mice in both CON groups were given equal volumes of phosphate-buffered saline (PBS) by lavage. At the end of the intervention, we assessed body fat and the parameters of glucose and lipid metabolism in the plasma, liver and skeletal muscle tissues as well as the levels of aldose reductase (AR) and transforming growth factor-β1 (TGF-β1) in the kidneys and measured adiponectin receptors and the protein expression of their signaling molecules in liver and muscle tissues. After 12 weeks of intervention, compared with the db/db-CON group, the percentage of body fat, fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) in the db/db-CGA group were all significantly decreased; TGF-β1 protein expression and AR activity in the kidney were both decreased; and the adiponectin level in visceral adipose was increased. The protein expression of adiponectin receptors (ADPNRs), the phosphorylation of AMP-activated protein kinase (AMPK) in the liver and muscle, and the mRNA and protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) in the liver were all significantly greater. CGA could lower the levels of fasting plasma glucose and HbA1c during late diabetes and improve kidney fibrosis to some extent through the modulation of adiponectin receptor signaling pathways in db/db mice. PMID:25849026

The effect of vitamin D supplementation on insulin resistance, visceral fat and adiponectin in vitamin D deficient women with polycystic ovary syndrome: a randomized placebo-controlled trial.

PubMed

Seyyed Abootorabi, Maryam; Ayremlou, Parvin; Behroozi-Lak, Tahereh; Nourisaeidlou, Sakineh

2018-06-01

Low plasma 25-hydroxy-vitamin D (25OHD) is associated with polycystic ovary syndrome (PCOS). Vitamin D deficiency may contribute to the development of insulin resistance, visceral fat and low level of adiponectin which are common feature in PCOS women. This study aimed to evaluate the effect of vitamin D supplementation on insulin resistance, visceral fat, and adiponectin in hypovitaminosis D women with polycystic ovary syndrome. In this randomized, placebo-controlled clinical trial, 44 PCOS women aged 20-38 years with plasma 25OHD <20 ng/mL were randomized in the intervention or placebo groups and followed for 8 weeks. Participants received 50,000 IU of oral vitamin D3 once weekly in the intervention group or placebo. The visceral adipose tissue, Insulin resistance (HOMA-IR), HOMA-B, QUICKI, and circulating adiponectin were compared before and after the intervention within groups using paired tests and the mean changes were analyzed between two groups by independent t-test. Of 44 eligible participates, 36 patients (81.8%) completed the study. After 8 week intervention, vitamin D supplementation compared to the placebo group significantly decreased fasting plasma glucose (FPG) (7.67 ± 7.66 versus 1.71 ± 7.50 mg/dL, p = .001) and significantly increased homeostasis model of assessment-estimated B cell function (HOMA-B) (129.76 ± 121.02 versus 48.32 ± 128.35, p = .014), Adiponectin (5.17 ± 8.09 versus -5.29 ± 8.64 mg/dL, p = .001), and serum vitamin D level (28.24 ± 6.47 versus 3.55 ± 4.25 ng/mL, p = .001). Vitamin D supplementation in vitamin D deficient women with PCOS, improved the FPG, HOMA-B, Adiponectin, and serum vitamin D level.

High Fat Diet Attenuates the Anticontractile Activity of Aortic PVAT via a Mechanism Involving AMPK and Reduced Adiponectin Secretion

PubMed Central

Almabrouk, Tarek A. M.; White, Anna D.; Ugusman, Azizah B.; Skiba, Dominik S.; Katwan, Omar J.; Alganga, Husam; Guzik, Tomasz J.; Touyz, Rhian M.; Salt, Ian P.; Kennedy, Simon

2018-01-01

Background and aim: Perivascular adipose tissue (PVAT) positively regulates vascular function through production of factors such as adiponectin but this effect is attenuated in obesity. The enzyme AMP-activated protein kinase (AMPK) is present in PVAT and is implicated in mediating the vascular effects of adiponectin. In this study, we investigated the effect of an obesogenic high fat diet (HFD) on aortic PVAT and whether any changes involved AMPK. Methods: Wild type Sv129 (WT) and AMPKα1 knockout (KO) mice aged 8 weeks were fed normal diet (ND) or HFD (42% kcal fat) for 12 weeks. Adiponectin production by PVAT was assessed by ELISA and AMPK expression studied using immunoblotting. Macrophages in PVAT were identified using immunohistochemistry and markers of M1 and M2 macrophage subtypes evaluated using real time-qPCR. Vascular responses were measured in endothelium-denuded aortic rings with or without attached PVAT. Carotid wire injury was performed and PVAT inflammation studied 7 days later. Key results: Aortic PVAT from KO and WT mice was morphologically indistinct but KO PVAT had more infiltrating macrophages. HFD caused an increased infiltration of macrophages in WT mice with increased expression of the M1 macrophage markers Nos2 and Il1b and the M2 marker Chil3. In WT mice, HFD reduced the anticontractile effect of PVAT as well as reducing adiponectin secretion and AMPK phosphorylation. PVAT from KO mice on ND had significantly reduced adiponectin secretion and no anticontractile effect and feeding HFD did not alter this. Wire injury induced macrophage infiltration of PVAT but did not cause further infiltration in KO mice. Conclusions: High-fat diet causes an inflammatory infiltrate, reduced AMPK phosphorylation and attenuates the anticontractile effect of murine aortic PVAT. Mice lacking AMPKα1 phenocopy many of the changes in wild-type aortic PVAT after HFD, suggesting that AMPK may protect the vessel against deleterious changes in response to HFD. PMID:29479319

Globular adiponectin inhibits ethanol-induced reactive oxygen species production through modulation of NADPH oxidase in macrophages: involvement of liver kinase B1/AMP-activated protein kinase pathway.

PubMed

Kim, Mi Jin; Nagy, Laura E; Park, Pil-Hoon

2014-09-01

Adiponectin, an adipokine predominantly secreted from adipocytes, has been shown to play protective roles against chronic alcohol consumption. Although excessive reactive oxygen species (ROS) production in macrophages is considered one of the critical events for ethanol-induced damage in various target tissues, the effect of adiponectin on ethanol-induced ROS production is not clearly understood. In the present study, we investigated the effect of globular adiponectin (gAcrp) on ethanol-induced ROS production and the potential mechanisms underlying these effects of gAcrp in macrophages. Here we demonstrated that gAcrp prevented ethanol-induced ROS production in both RAW 264.7 macrophages and primary murine peritoneal macrophages. Globular adiponectin also inhibited ethanol-induced activation of NADPH oxidase. In addition, gAcrp suppressed ethanol-induced increase in the expression of NADPH oxidase subunits, including Nox2 and p22(phox), via modulation of nuclear factor-κB pathway. Furthermore, pretreatment with compound C, a selective inhibitor of AMPK, or knockdown of AMPK by small interfering RNA restored suppression of ethanol-induced ROS production and Nox2 expression by gAcrp. Finally, we found that gAcrp treatment induced phosphorylation of liver kinase B1 (LKB1), an upstream signaling molecule mediating AMPK activation. Knockdown of LKB1 restored gAcrp-suppressed Nox2 expression, suggesting that LKB1/AMPK pathway plays a critical role in the suppression of ethanol-induced ROS production and activation of NADPH oxidase by gAcrp. Taken together, these results demonstrate that globular adiponectin prevents ethanol-induced ROS production, at least in part, via modulation of NADPH oxidase in macrophages. Further, LKB1/AMPK axis plays an important role in the suppression of ethanol-induced NADPH oxidase activation by gAcrp in macrophages. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

The mechanism of exogenous adiponectin in the prevention of no-reflow phenomenon in type 2 diabetic patients with acute myocardial infarction during PCI treatment.

PubMed

Zhang, C-J; Deng, Y-Z; Lei, Y-H; Zhao, J-B; Wei, W; Li, Y-H

2018-04-01

To investigate the mechanism of exogenous adiponectin in the prevention of no-reflow phenomenon in type 2 diabetic (T2DM) patients with acute myocardial infarction (AMI) during percutaneous coronary intervention (PCI) treatment. 66 patients were randomly divided into control group and observation group, 33 cases in each group. According to the percutaneous coronary intervention (PCI) emergency treatment principle, patients from the control group were treated with an intracoronary injection of adenosine combined with a micro-pump intravenous infusion of tirofiban. Patients from the observation group were injected with exogenous adiponectin in addition to the adenosine and tirofiban treatments. There were no significant differences in gender, age, location of the target lesion, degree of stenosis, stent implantation number, length and the inner diameter between control and observation group (p > 0.05). Lower frequent of slow blood flow and no-reflow and shorter interventional procedures were observed in observation group compared with those of control group (p < 0.05). Moreover, the increase of plasma creatine kinase (CK-MB) in patients of observation group was lower than that of the patients in control group (p < 0.05). In addition, the levels of troponin-I (cTnI), IL-6, TNF- α, endothelin-1 (ET-1), vascular endothelial adhesion molecular I (VCAM-1) and bax/Bcl-2 were significantly lower in observation group than those in control (p < 0.05). Furthermore, the occurrence of major adverse cardiac events (MACE) during a 12-month follow-up was significantly lower in the observation group than that of control (p < 0.05). Exogenous adiponectin further reduced the no-reflow phenomenon during PCI treatment of the patients with T2DM combined with AMI. The function of exogenous adiponectin is associated with the reduced myocardial and endothelial cell injury and the inhibited inflammation and apoptosis. The application of exogenous adiponectin can significantly improve the clinical outcomes.

The Association of SNP276G>T at Adiponectin Gene with Insulin Resistance and Circulating Adiponectin in Morbid Obese Patients After a Biliopancreatic Diversion Surgery.

PubMed

de Luis, Daniel Antonio; Pacheco, David; Primo, D; Izaola, Olatz; Aller, R

2017-12-01

The effects of rs1501299 variant of ADIPO gene on weight loss after bariatric surgery have not been evaluated. We decided to investigate the role of this genetic variant on anthropometric and biochemical outcomes such as serum adiponectin levels after biliopancreatic diversion (BPD) surgery in morbidly obese patients during 3 years. A sample of 64 patients with morbid obesity without diabetes mellitus was operated. Biochemical and anthropometric evaluation were realized at basal visit and at each visit during 3 years (1, 2, and 3 years). Percent excess weight loss, body mass index, weight, waist circumference, fat mass, blood pressure, fasting glucose, LDL cholesterol, total cholesterol, and triglycerides levels improved in both genotype groups. Fasting insulin levels and HOMA-IR decreased significantly only in non-T allele carriers. The decrease of fasting insulin levels at 3 years (delta -9.2 ± 3.4 vs -2.9 ± 2.2 mUI/L; p = 0.01) and HOMA-IR (delta -1.3 ± 0.3 vs -0.8 ± 0.4 units; p = 0.03) were higher in non-T allele carriers than T carriers. Adiponectin levels increased in all times after surgery in non-T allele carriers, too. The increase of adiponectin levels at 3 years (delta 12.2 ± 3.6 vs 1.8 ± 1.2 ng/mL; p = 0.01) was higher in non-T allele carriers than T carriers. Non-T allele of ADIPOQ gene variant (rs1501299) is associated with increases in adiponectin levels and better improvements of insulin and HOMA-IR after BPD massive weight loss. These parameters remained unchanged in T allele carriers.

Effects of 17β-estradiol and progesterone on the production of adipokines in differentiating 3T3-L1 adipocytes: Role of Rho-kinase.

PubMed

Pektaş, Mehtap; Kurt, Akif Hakan; Ün, İsmail; Tiftik, Rukiye Nalan; Büyükafşar, Kansu

2015-04-01

Effect of female sex hormones on the production/release of adipocyte-derived cytokines has been debatable. Furthermore, whether the cellular signaling triggered by these hormones involve Rho-kinase has not been investigated yet. Therefore, in this study, effects of 17β-estradiol and progesterone as well as the Rho-kinase inhibitor, Y-27632 on the level of adipokines such as resistin, adiponectin, leptin, TNF-α and IL-6 were investigated in 3T3-L1-derived adipocytes. Differentiation was induced in the post-confluent preadipocytes by the standard differentiation medium (Dulbecco's modified Eagle's medium with 10% fetal bovine serum together with the mixture of isobutylmethylxanthine, dexamethasone and insulin) in the presence of 17β-estradiol (10(-8)-10(-7)M), progesterone (10(-6)-10(-5)M), the Rho-kinase inhibitor, Y-27632 (10(-5)M) and their combination for 8days. Measurements of the adipokines were performed in the culturing medium by ELISA kits using specific monoclonal antibodies. 17β-estradiol elevated resistin but decreased adiponectin and IL-6 levels; however, it did not alter the concentration of leptin and TNF-α. Y-27632 pretreatment inhibited the rise of resistin and the fall of adiponectin by 17β-estradiol without any effects by its own. Progesterone did not change resistin, leptin and TNF-α level; however, it elevated adiponectin and decreased IL-6 production. Neither 17β-estradiol nor Y-27632 was able to antagonize the increase of adiponectin and the reduction of IL-6 levels by progesterone. While Y-27632 alone lowered IL-6 level, it increased leptin and TNF-α concentration without altering resistin and adiponectin. In conclusion, 17β-estradiol could modify adipokine production in 3T3-L1 adipocytes with the actions some of which involve Rho-kinase mediation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pharmacodynamic Effects of Low-Dose Pioglitazone in Patients with the Metabolic Syndrome without Diabetes Mellitus.

PubMed

Vu, Anh; Kosmiski, Lisa A; Beitelshees, Amber L; Prigeon, Ronald; Sidhom, Maha S; Bredbeck, Brooke; Predhomme, Julie; Deininger, Kimberly M; Aquilante, Christina L

2016-03-01

To determine the effects of low-dose pioglitazone on plasma adipocyte-derived cytokines, high-sensitivity C-reactive protein (hs-CRP), and components of the metabolic syndrome in adults with the metabolic syndrome without diabetes mellitus. Prospective, randomized, double-blind, placebo-controlled study. University of Colorado Clinical and Translational Research Center. Thirty-two men and women, aged 30-60 years, without diabetes who had a clinical diagnosis of the metabolic syndrome, as defined by the American Heart Association/National Heart, Lung, and Blood Institute criteria. Patients were randomly assigned to receive oral pioglitazone 7.5 mg daily or matching placebo for 8 weeks. The primary end point was the change in plasma high-molecular-weight (HMW) adiponectin level from baseline to week 8. Other end points were changes in plasma total adiponectin, omentin, and hs-CRP levels, and changes in components of the metabolic syndrome (e.g., insulin sensitivity) from baseline to week 8. Pioglitazone was associated with a significant increase in plasma HMW adiponectin from baseline to week 8 compared with placebo (+47% vs -10%, p<0.001). Insulin sensitivity increased significantly from baseline to week 8 in the pioglitazone group (+88%, p=0.02) but not in the placebo group (+15%, p=0.14). Change in HMW adiponectin was significantly correlated with the change in insulin sensitivity in the pioglitazone group (r = 0.784, p=0.003). No significant differences in mean percentage changes in plasma total adiponectin, omentin, and hs-CRP levels were observed between the pioglitazone and placebo groups. Likewise, changes in body weight, insulin sensitivity, glucose, lipids, and blood pressure did not differ significantly between the groups. Low-dose pioglitazone favorably modulates plasma HMW adiponectin, which was associated with an improvement in insulin sensitivity, in patients with the metabolic syndrome without diabetes. © 2016 Pharmacotherapy Publications, Inc.

Direct effects of leptin and adiponectin on peripheral reproductive tissues: a critical review

PubMed Central

Kawwass, Jennifer F.; Summer, Ross; Kallen, Caleb B.

2015-01-01

Obesity is a risk factor for infertility and adverse reproductive outcomes. Adipose tissue is an important endocrine gland that secretes a host of endocrine factors, called adipokines, which modulate diverse physiologic processes including appetite, metabolism, cardiovascular function, immunity and reproduction. Altered adipokine expression in obese individuals has been implicated in the pathogenesis of a host of health disorders including diabetes and cardiovascular disease. It remains unclear whether adipokines play a significant role in the pathogenesis of adverse reproductive outcomes in obese individuals and, if so, whether the adipokines are acting directly or indirectly on the peripheral reproductive tissues. Many groups have demonstrated that receptors for the adipokines leptin and adiponectin are expressed in peripheral reproductive tissues and that these adipokines are likely, therefore, to exert direct effects on these tissues. Many groups have tested for direct effects of leptin and adiponectin on reproductive tissues including the testis, ovary, uterus, placenta and egg/embryo. The hypothesis that decreased fertility potential or adverse reproductive outcomes may result, at least in part, from defects in adipokine signaling within reproductive tissues has also been tested. Here, we present a critical analysis of published studies with respect to two adipokines, leptin and adiponectin, for which significant data have been generated. Our evaluation reveals significant inconsistencies and methodological limitations regarding the direct effects of these adipokines on peripheral reproductive tissues. We also observe a pervasive failure to account for in vivo data that challenge observations made in vitro. Overall, while leptin and adiponectin may directly modulate peripheral reproductive tissues, existing data suggest that these effects are minor and non-essential to human or mouse reproductive function. Current evidence suggests that direct effects of leptin or adiponectin on peripheral reproductive tissues are unlikely to factor significantly in the adverse reproductive outcomes observed in obese individuals. PMID:25964237

Relationships between markers of inflammation and bone density: findings from the Hertfordshire Cohort Study.

PubMed

Fuggle, N R; Westbury, L D; Syddall, H E; Duggal, N A; Shaw, S C; Maslin, K; Dennison, E M; Lord, J; Cooper, C

2018-05-28

Among 365 Hertfordshire Cohort Study participants (aged 59-71 years at baseline), higher adiponectin and adiponectin to leptin ratios were associated with lower baseline lumbar spine and femoral neck bone mineral density (BMD). Lower IL-10 was associated with accelerated decline in lumbar spine BMD. This suggests that bone health can be influenced by changes in immune phenotype and alterations in adipokine homeostasis. The aim of this study was to examine the association between indices of inflammation and BMD in a population-based cohort of older adults in the UK. Analyses were based on a sample of 194 men and 171 women of the Hertfordshire Cohort Study (community-living, older adults). Dual energy X-ray absorptiometry (DXA) was performed at the lumbar spine and proximal femur at baseline and repeated at a median of 4.5 years (inter-quartile range 3.6 to 5.2). Inflammatory markers (CRP, TNF, IL-1β, IL-6, IL-8, IL-10, adiponectin and leptin) were ascertained at baseline using enzyme-linked immunosorbent assay (ELISA) techniques and Bio-Plex Pro Assays. Gender-adjusted linear regression was used to examine the associations between markers of inflammation and outcomes with and without adjustment for anthropometric and lifestyle factors. The mean (SD) ages at baseline were 64.4 (2.5) and 66.5 (2.7) years for men and women respectively. Higher levels of adiponectin and adiponectin to leptin ratios were each associated with lower baseline lumbar spine and femoral neck BMD in gender-adjusted (p < 0.01) and fully adjusted (p < 0.05) analyses. Lower levels of IL-10 and TNF were each associated with accelerated decline in lumbar spine BMD in both gender-adjusted (p ≤ 0.05) and fully adjusted (p < 0.05) analyses. In a cohort of older adults, high levels of adiponectin and adiponectin to leptin ratios were both associated with lower BMD at the lumbar spine and femoral neck at baseline, and lower IL-10 was associated with accelerated decline in BMD at the lumbar spine. This adds weight to the theory that bone health can be influenced by changes in immune phenotype and alterations in adipokine homeostasis.

Body and liver fat content and adipokines in schizophrenia: a magnetic resonance imaging and spectroscopy study.

PubMed

Kim, Jong-Hoon; Kim, Jung-Hyun; Park, Pil-Whan; Machann, Jürgen; Roden, Michael; Lee, Sheen-Woo; Hwang, Jong-Hee

2017-06-01

Although antipsychotic treatment often causes weight gain and lipid abnormalities, quantitative analyses of tissue-specific body fat content and its distribution along with adipokines have not been reported for antipsychotic-treated patients. The purposes of the present study were to quantitatively assess abdominal and liver fat in patients with schizophrenia on antipsychotic treatment and age- and body mass index (BMI)-matched healthy controls and to evaluate their associations with plasma leptin and adiponectin levels. In 13 schizophrenia patients on antipsychotic treatment and 11 age- and BMI-matched controls, we simultaneously quantified visceral and subcutaneous fat content using T1-weighted magnetic resonance imaging and liver fat content by 1 H magnetic resonance spectroscopy. Associations of tissue-specific fat content with plasma levels of leptin and adiponectin were evaluated. Plasma adiponectin level (μg/mL) was not statistically different between groups (7.02 ± 2.67 vs. 7.59 ± 2.92), whereas plasma leptin level (ng/mL) trended to be higher in patients than in controls (11.82 ± 7.89 vs. 7.93 ± 5.25). The values of liver fat (%), visceral fat (L), and subcutaneous fat (L) were 9.64 ± 8.03 vs. 7.07 ± 7.35, 4.41 ± 1.64 vs. 3.31 ± 1.97, and 8.37 ± 3.34 vs. 7.16 ± 2.99 in patients vs. controls, respectively. Liver fat content was inversely correlated with adiponectin in controls (r =  - 0.87, p < 0.001) but not in patients (r =  - 0.26, p = 0.39). In both groups, visceral fat was inversely associated with adiponectin (controls : r =  - 0.66, p = 0.03; patients : r =  - 0.65, p = 0.02), while subcutaneous fat was positively correlated with leptin (controls : r = 0.90, p < 0.001; patients : r = 0.67, p = 0.01). These findings suggest that antipsychotic treatment may disrupt the physiological relationship between liver fat content and adiponectin but does not essentially affect the associations of adiponectin and leptin with visceral and subcutaneous compartments.

l-Cysteine supplementation increases insulin sensitivity mediated by upregulation of GSH and adiponectin in high glucose treated 3T3-L1 adipocytes.

PubMed

Achari, Arunkumar E; Jain, Sushil K

2017-09-15

Diabetic patients have lower blood levels of l-cysteine (LC) and glutathione (GSH). This study examined the hypothesis that LC supplementation positively up regulates the effects of insulin on GSH and glucose metabolism in 3T3-L1 adipocyte model. 3T3L1 adipocytes were treated with LC (250 μM, 2 h) and/or insulin (15 or 30 nM, 2 h), and high glucose (HG, 25 mM, 20 h). Results showed that HG caused significant increase (95%) in ROS and reduction in the protein levels of DsbA-L (43%), adiponectin (64%), GCLC (20%), GCLM (21%), GSH (50%), and GLUT-4 (23%) in adipocytes. Furthermore, HG caused a reduction in total (35%) and HMW adiponectin (30%) secretion. Treatment with insulin alone significantly (p < 0.05) reduced ROS levels as well as increased DsbA-L, adiponectin, GCLC, GCLM, GSH, and GLUT-4 protein levels, glucose utilization, and improved total and HMW adiponectin secretion in HG treated adipocytes compared to HG alone. Interestingly, LC supplementation along with insulin caused greater reduction in ROS levels and significantly (p < 0.05) boosted the DsbA-L (41% vs LC, 29% vs Insulin), adiponectin (92% Vs LC, 84% Vs insulin) protein levels and total (32% Vs LC, 22% Vs insulin) and HMW adiponectin (75% Vs LC, 39% Vs insulin) secretion compared with the either insulin or LC alone in HG-treated cells. In addition, LC supplementation along with insulin increased GCLC (21% Vs LC, 14% insulin), GCLM (28% Vs LC, 16% insulin) and GSH (25% Vs LC and insulin) levels compared with the either insulin or LC alone in HG-treated cells. Furthermore, LC and insulin increases GLUT-4 protein expression (65% Vs LC, 18% Vs Insulin), glucose utilization (57% Vs LC, 27% Vs insulin) compared with the either insulin or LC alone in HG-treated cells. Similarly, LC supplementation increased insulin action significantly in cells maintained in medium contained control glucose. To explore the beneficial effect of LC is mediated by the upregulation of GCLC, we knocked down GCLC using siRNA in adipoctyes. There was a significant decrease in DsbA-L and GLUT-4 mRNA levels and GSH levels in GCLC knockdown adipocytes and LC supplementation up regulates GCLC, DsbA-L and GLUT-4 mRNA expression and GSH levels in GCLC knockdown cells. These results demonstrated that LC along with insulin increases GSH levels thereby improving adiponectin secretion and glucose utilization in adipocytes. This suggests that LC supplementation can increase insulin sensitivity and can be used as an adjuvant therapy for diabetes. Copyright © 2017. Published by Elsevier Inc.

Association of serum leptin and adiponectin with anthropomorphic indices of obesity, blood lipids and insulin resistance in a Sub-Saharan African population.

PubMed

Ayina, Clarisse Noël A; Noubiap, Jean Jacques N; Etoundi Ngoa, Laurent Serge; Boudou, Philippe; Gautier, Jean François; Mengnjo, Michel Karngong; Mbanya, Jean Claude; Sobngwi, Eugene

2016-05-17

There is little data on the metabolic effects of adipokines in sub-Saharan African populations. This study aimed to explore the potential relationship of leptin and adiponectin, with obesity, plasma lipids and insulin resistance in a Cameroonian population. We enrolled 167 men and 309 women aged ≥18 years from the general population in Cameroon. Data were collected on waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), body fat (BF%), fasting blood glucose, plasma lipids, adiponectin, leptin, insulin and homeostasis model for assessment of insulin resistance (HOMA-IR). Pearson's correlation and multiple stepwise linear regression analyses were used to determine correlates of leptin and adiponectin serum levels. The prevalence of obesity was higher in women compared to men (p < 0.0001), and Central obesity which is more prevalent particularly in women (WC = 42.4%, WHR = 42.3%), is almost for 90% comparable to %BF (42.7%). Adiponectin negatively with BMI (r = -0.294, p < 0.0001), WC (r = -0.294, p < 0.0001), %BF (r = -0.122, p = 0.028), WHR (r = -0.143, p = 0.009), triglycerides (r = -0.141, p = 0.011), HOMA-IR (r = -0.145, p = 0.027) and insulin (r = -0.130, p = 0.048). Leptin positively correlated with BMI (r = 0.628), WC (r = 0.530), BF% (r = 0.720), (all p < 0.0001); with DBP (r = 0.112, p = 0.043), total cholesterol (r = 0.324, p < 0.0001), LDL-cholesterol (r = 0.298, p < 0.0001), insulin (r = 0.320, p < 0.001 and HOMA-IR (r = 0.272, p < 0.0001). In multiple stepwise regression analysis, adiponectin was negatively associated with WC (β = -0.38, p = 0.001) and BF% (β = 0.33, p < 0.0001), while leptin was positively associated with BF% (β = 0.60, p < 0.0001), total cholesterol (β = 0.11, p = 0.02) and HOMA-IR (β = 0.11, p = 0.02). When controlled for gender, HOMA-IR was found significantly associated to adiponectin (β = 0.13, p = 0.046), but not BF%, while the association previously found between leptin and HOMA-IR disappeared; BMI and WC were significantly associated with leptin (β = 0.18, p = 0.04 & β = 0.19, p = 0.02 respectively). This study, which includes a population who was not receiving potentially confounding medications, confirms the associations previously observed of adiponectin with reduced adiposity especially central adiposity and improved insulin sensitivity. Confirmatory associations were also observed between leptin and obesity, blood lipids and insulin resistance for the first time in an African population. Gender was significant covariate interacting with insulin sensitivity/insulin resistance and obesity indexes associations in this population.

Endogenous hormones, inflammation, and body size in premenopausal Mexican women: results from the Mexican Teachers' Cohort (MTC, ESMaestras).

PubMed

Rinaldi, Sabina; Biessy, Carine; de la Luz Hernandez, Maria; Lajous, Martin; Ortiz-Panozo, Eduardo; Yunes, Elsa; Lopez-Ridaura, Ruy; Torres-Mejia, Gabriela; Romieu, Isabelle

2015-03-01

Obesity is a major risk factor for several cancers, including female cancers. Endogenous hormones and inflammatory factors may mediate the association between anthropometric measures and cancer risk, although these associations have been studied mainly in Caucasians. The aim of the current study was to explore the association of circulating hormones, adipokines, and inflammatory factors with obesity and overweight in premenopausal Mexican women. We conducted a cross-sectional analysis of 504 premenopausal women from the large Mexican Teachers' Cohort (MTC, ESMaestras) study to determine the association of insulin-like growth factor I (IGF-I), its major circulating binding protein (IGFBP-3), leptin, adiponectin, C-peptide, and C-reactive protein with comprehensive measures of body size. Biomarkers were measured by immunoassays. Multivariate regression analyses were performed to compare geometric mean biomarker concentrations with measured markers of body size and adiposity. Mean IGF-I and IGFBP-3 concentrations significantly increased with increasing height and leg length. Concentrations of IGF-I, adiponectin, and the IGF-I/IGFBP-3 ratio strongly decreased with increasing BMI, weight, waist and hip circumferences, waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR), while CRP, leptin, C-peptide concentrations, and the leptin/adiponectin ratio strongly increased. Adiponectin and the leptin/adiponectin ratio remained significantly related to measures of central adiposity (waist circumference, WHpR, and WHtR) after adjustment by body mass index. The results of our study suggest a strong relation between biomarkers and body size in this study population and suggest that different fat depots may have different metabolic properties.

Roles of oxidative stress, adiponectin, and nuclear hormone receptors in obesity-associated insulin resistance and cardiovascular risk.

PubMed

Matsuda, Morihiro; Shimomura, Iichiro

2014-08-01

Obesity leads to the development of type 2 diabetes mellitus, which is a strong risk factor for cardiovascular disease. A better understanding of the molecular basis of obesity will lead to the establishment of effective prevention strategies for cardiovascular diseases. Adipocytes have been shown to generate a variety of endocrine factors termed adipokines/adipocytokines. Obesity-associated changes to these adipocytokines contribute to the development of cardiovascular diseases. Adiponectin, which is one of the most well-characterized adipocytokines, is produced exclusively by adipocytes and exerts insulin-sensitizing and anti-atherogenic effects. Obese subjects have lower levels of circulating adiponectin, and this is recognized as one of the factors involved in obesity-induced insulin resistance and atherosclerosis. Another pathophysiological feature of obesity may involve the low-grade chronic inflammation in adipose tissue. This inflammatory process increases oxidative stress in adipose tissue, which may affect remote organs, leading to the development of diabetes, hypertension, and atherosclerosis. Nuclear hormone receptors (NRs) regulate the transcription of the target genes in response to binding with their ligands, which include metabolic and nutritional substrates. Among the various NRs, peroxisome proliferator-activated receptor γ promotes the transcription of adiponectin and antioxidative enzymes, whereas mineralocorticoid receptor mediates the effects of aldosterone and glucocorticoid to induce oxidative stress in adipocytes. It is hypothesized that both play crucial roles in the pathophysiology of obesity-associated insulin resistance and cardiovascular diseases. Thus, reduced adiponectin and increased oxidative stress play pathological roles in obesity-associated insulin resistance to increase the cardiovascular disease risk, and various NRs may be involved in this pathogenesis.

Pro-inflammatory and atherogenic circulating factors in non-alcoholic fatty liver disease associated to metabolic syndrome.

PubMed

Lucero, Diego; Zago, Valeria; López, Graciela I; Graffigna, Mabel; Fainboim, Hugo; Miksztowicz, Verónica; Meroño, Tomás; Belli, Susana; Levalle, Oscar; Wikinski, Regina; Brites, Fernando; Berg, Gabriela; Schreier, Laura

2011-01-14

It is not elucidated if liver fat deposits associated to metabolic syndrome (MS) aggravate the atherogenic state. We evaluated, in MS patients, if the presence of non-alcoholic hepatic steatosis (HS) determines differences in inflammatory markers and VLDL characteristics. Seventy-five patients with MS were divided into 2 groups depending on the presence or absence of HS, assessed by ultrasound. Lipid profile, free fatty acids (FFA), VLDL composition, adiponectin, tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), and soluble adhesion molecules (sVCAM-1 and sICAM-1) were measured. HS patients presented increased triglycerides levels, HOMA-IR and FFA. Patients with HS showed a reduction in adiponectin (p = 0.04) and increase in hs-CRP (p = 0.02), independently of insulin-resistance (IR). FFA correlated positively with TNF-α (p = 0.04) and inversely with adiponectin (p = 0.01). hs-CRP correlated with all inflammatory markers, independently of IR: TNF-α (r = 0.34, p = 0.02), sVCAM-1 (r = 0.29 p = 0.03), sICAM-1 (r = 0.56, p = 0.01), adiponectin (r = -0.34, p = 0.04). HS patients presented higher VLDL mass and number of particles. Adiponectin correlated with VLDL cholesterol content (r = -0.47, p = 0.04), independently of IR. VLDL, once secreted, would suffer from changes, becoming more atherogenic. Simple HS would play an important role increasing cardiovascular risk, independently of IR. hs-CRP may represent a useful biomarker of this condition. Copyright © 2010 Elsevier B.V. All rights reserved.

Influence of endurance and sprinting exercise on plasma adiponectin, leptin and irisin concentrations in racing Greyhounds and sled dogs.

PubMed

Bell, M A; Levine, C B; Downey, R L; Griffitts, C; Mann, S; Frye, C W; Wakshlag, J J

2016-05-01

The objective of this study was to assess the effects of both short-term anaerobic exercise and long-term aerobic exercise on leptin, adiponectin and irisin concentrations in both sprint and endurance canine athletes. Prospective field trial repeated measures. The 25 racing Greyhounds were run over 400 m, with blood samples collected prior to exercise and at 10 min and 120 min after exercise. The 16 sled dogs were run an average of 3.5-5 h/day on 5 out of 8 days of stage stop racing competition, with assessment on days 0, 2 and 8. Baseline leptin concentrations were found to be lower than previously recorded values of domestic dogs, possibly because of a lower body fat content in athletes, with concentrations in sled dogs being slightly higher than those in Greyhounds. Baseline adiponectin concentrations in both groups of dogs, on average, were lower than most previously recorded values in domestic dogs; although unexpected, these findings may be attributed to differences in body fat content of the study population. Endurance exercise in sled dogs resulted in a persistent decrease in leptin that appears to be independent of race-associated weight loss, with no appreciable changes in adiponectin or irisin concentrations. The anaerobic exercise of Greyhounds produced no detectable changes in leptin and adiponectin concentrations; however, a significant rise in irisin 10 min post-exercise may be a compensatory mechanism for restoration of ATP homeostasis in skeletal muscle. © 2016 Australian Veterinary Association.

Serum adipokines, adipose tissue measurements and metabolic parameters in patients with advanced radiographic knee osteoarthritis.

PubMed

Toussirot, Eric; Michel, Fabrice; Béreau, Matthieu; Dehecq, Barbara; Gaugler, Béatrice; Wendling, Daniel; Grandclément, Emilie; Saas, Philippe; Dumoulin, Gilles

2017-11-01

We conducted the present study to evaluate the serum levels of adipokines (leptin, total and high molecular adiponectin, resistin), a marker of cartilage breakdown (C2C), and ghrelin together with body composition in patients with knee osteoarthritis (OA). Fifty patients and 50 sex-matched healthy subjects (HS) were evaluated. Knee OA was scored according to the Kellgren-Lawrence (KL) grade. Body composition parameters including lean mass and measurements of fat mass (total fat, adiposity, fat in the android and gynoid regions, visceral fat and trunk/legs fat ratio) were obtained using dual energy X-ray absorptiometry. Most of the recruited patients (88%) had advanced knee OA with KL grade 3 or 4. The patients had higher body mass index than HS (p < 0.0001). Serum leptin, high molecular adiponectin, resistin and ghrelin levels did not differ between patients and HS. Total adiponectin was higher in women with OA compared to women from the HS group (p = 0.004). Total fat mass, adiposity and measurements of central adiposity (fat in the android region, trunk/lower limbs fat ratio and visceral fat) were increased in patients with knee OA (all p < 0.05). Total adiponectin was borderline associated with the severity of OA. Our results show that total adiponectin is significantly increased in women with advanced knee OA. Independently of gender, patients with severe knee OA were characterized by a significant excess of fat with a distribution toward the visceral region. This abnormal body composition may contribute to the cardiometabolic profile that is described in patients with knee OA.

Sexual dimorphism in interleukin 17A and adipocytokines and their association with insulin resistance among obese adolescents in Yogyakarta, Indonesia.

PubMed

Susilowati, Rina; Sulistyoningrum, Dian Caturini; Witari, Ni Putu Diah; Huriyati, Emy; Luglio, Harry Freitag; Julia, Madarina

2016-12-01

Pro-inflammatory cytokines interleukin 17A (IL-17), leptin, and adiponectin have been associated with obesity and insulin resistance. Moreover, differences in sex and ethnicity as well as plasma concentration of adipocytokines and cytokines have been associated with the risk of insulin resistance. This study was conducted to elucidate whether sex differences exist in the risk of insulin resistance in Indonesian adolescents and to determine how plasma leptin, adiponectin, and IL-17 predict insulin resistance. The study participants were 69 obese-overweight boys, 53 obese-overweight girls, 59 non-obese boys, and 50 non-obese girls aged 15-18 years. Insulin resistance was determined using the homeostatic model assessment of insulin resistance index. Plasma IL-17, leptin, and adiponectin were measured using ELISA. Data were analysed using one-way ANOVA and linear regression analysis. Odd ratios [ORs; 95% confidence intervals (CIs)] were analysed to estimate the risk of insulin resistance; the significance level was set at 95%. The OR (95% CI) for insulin resistance was higher in obese-overweight boys than in obese-overweight girls. The plasma IL-17 was higher in boys, whereas plasma adiponectin and leptin were significantly higher in girls. In all participants, obesity status and plasma leptin were the most efficient predictors of insulin resistance, whereas the IL-17 could not significantly predict insulin resistance. Sexual dimorphism exists in IL17 as well as leptin and adiponectin in adolescents. Plasma IL-17 cannot be used to predict insulin resistance in adolescents of both sex.

Nutritional Ingredients Modulate Adipokine Secretion and Inflammation in Human Primary Adipocytes

PubMed Central

Romacho, Tania; Glosse, Philipp; Richter, Isabel; Elsen, Manuela; Schoemaker, Marieke H.; van Tol, Eric A.; Eckel, Jürgen

2015-01-01

Nutritional factors such as casein hydrolysates and long chain polyunsaturated fatty acids have been proposed to exert beneficial metabolic effects. We aimed to investigate how a casein hydrolysate (eCH) and long chain polyunsaturated fatty acids could affect human primary adipocyte function in vitro. Incubation conditions with the different nutritional factors were validated by assessing cell vitality with lactate dehydrogenase (LDH) release and neutral red incorporation. Intracellular triglyceride content was assessed with Oil Red O staining. The effect of eCH, a non-peptidic amino acid mixture (AA), and long-chain polyunsaturated fatty acids (LC-PUFAs) on adiponectin and leptin secretion was determined by enzyme-linked immunosorbent assay (ELISA). Intracellular adiponectin expression and nuclear factor-κB (NF-κB) activation were analyzed by Western blot, while monocyte chemoattractant protein-1 (MCP-1) release was explored by ELISA. The eCH concentration dependently increased adiponectin secretion in human primary adipocytes through its intrinsic peptide bioactivity, since the non-peptidic mixture, AA, could not mimic eCH’s effects on adiponectin secretion. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and DHA combined with arachidonic acid (ARA) upregulated adiponectin secretion. However, only DHA and DHA/ARA exerted a potentanti-inflammatory effect reflected by prevention of tumor necrosis factor-α (TNF-α) induced NF-κB activation and MCP-1 secretion in human adipocytes. eCH and DHA alone or in combination with ARA, may hold the key for nutritional programming through their anti-inflammatory action to prevent diseases with low-grade chronic inflammation such as obesity or diabetes. PMID:25629558

Comparison of biochemical data, blood pressure and physical activity between longevity and non-longevity districts in Japan.

PubMed

Mori, Ichiro; Ishizuka, Tatsuo; Morita, Hiroyuki; Matsumoto, Masami; Uno, Yoshihiro; Kajita, Kazuo; Ikeda, Takahide; Fujioka, Kei; Matsubara, Kenji

2008-10-01

There is controversy about longevity-associated factors, including environmental and genetic factors. Clinical and epidemiological studies suggest that multiple risk factors decrease life-span, but there has not been a definitive report regarding the association of risk factors with longevity. The ultimate aim of the present study was to prevent the overwhelming increase in life-style-related diseases by evaluating this association in 2 districts in Japan. Plasma glucose levels, hemoglobin (Hb) A1c, lipids, dehydroepiandrosterone-sulfate, adiponectin and physical activity were examined in 133 subjects (M/F 47/86, 67+/-1 years) in Kokufu, a longevity district (mean life span: 80.4 years according to 2000 Japanese census) and 69 subjects (M/F 29/40, 62+/-1 years) in Miyama, a non-longevity district (mean life span 77.4 years, 2000 census). There were significant differences in systolic and diastolic blood pressures (BPs, p < 0.001), exercise capacity (p < 0.0001) and plasma adiponectin levels (p < 0.04) between the districts. Plasma adiponectin level was significantly correlated with high-density lipoprotein-cholesterol (HDL-C) (r = 0.333, p < 0.0001), triglyceride (TG) (r = -0.161, p < 0.04), HbA1c (r = -0.163, p < 0.03) and HOMA-R (r = -0.163, p < 0.03). Life-style-related factors such as BP, exercise capacity and plasma adiponectin levels might play an important role in longevity, and those of HDL-C and TG, as well as glucose tolerance, might be associated with adiponectin levels.

Experimental hyperthyroidism decreases gene expression and serum levels of adipokines in obesity.

PubMed

Luvizotto, Renata de Azevedo Melo; do Nascimento, André Ferreira; de Síbio, Maria Teresa; Olímpio, Regiane Marques Castro; Conde, Sandro José; Lima-Leopoldo, Ana Paula; Leopoldo, André Soares; Cicogna, Antonio Carlos; Nogueira, Célia Regina

2012-01-01

To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals. Male Wistar rats were randomly divided into two groups: control (C)-fed with commercial chow ad libitum-and obese (OB)-fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB) and obese with 25 μg triiodothyronine (T(3))/100 BW (OT). The T(3) dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin. T(3) treatment was effective, increasing fT(3) levels and decreasing fT(4) and TSH serum concentration. Administration of T(3) promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression. Our results suggest that T(3) modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T(3) and adipokines in obesity.

Adiponectin, Resistin, and Visfatin in Childhood Obesity and Exercise.

PubMed

Jamurtas, Athanasios Z; Stavropoulos-Kalinoglou, Antonios; Koutsias, Stilianos; Koutedakis, Yiannis; Fatouros, Ioannis

2015-11-01

Childhood obesity is increasing alarmingly, and a strong association with chronic diseases has been established. Specific adipokines are released from the adipose tissue and relate with chronic diseases even in the pediatric population. Adiponectin levels are lower in obesity and increase with decreasing body weight. A few pediatric studies examining a possible relationship between resistin and obesity do not provide a clear picture. Most studies agree that visfatin levels appear elevated in childhood obesity. Exercise seems to increase adiponectin levels whereas resistin levels are reduced. The lack of data on the effects of acute and chronic exercise on visfatin levels precludes us from making safe conclusions as to what the effects of exercise (acute or chronic) would be on visfatin levels in children. Clearly, exercise has an impact on the adipose tissue and the release of adiponectin, resistin, and visfatin. However, other factors affect the secretion rate of these adipokines from the adipose tissue; these factors should also be taken into consideration when examining the effects of exercise on adipokines. Gender, age, body composition, physical activity levels, mode and intensity of exercise are some of the factors that should be looked into in future studies.

Exercise, adipokines and pediatric obesity: a meta-analysis of randomized controlled trials.

PubMed

García-Hermoso, A; Ceballos-Ceballos, R J M; Poblete-Aro, C E; Hackney, A C; Mota, J; Ramírez-Vélez, R

2017-04-01

Adipokines are involved in the etiology of diabetes, insulin resistance, and the development of atherosclerosis and other latent-onset complications. The objective of this meta-analysis was to determine the effectiveness of exercise interventions on adipokines in pediatric obesity. A computerized search was made using three databases. The analysis was restricted to studies that examined the effect of exercise interventions on adipokines (adiponectin, leptin, resistin and visfatin) in pediatric obesity (6-18 years old). Fourteen randomized controlled trials (347 youths) were included. Weighted mean difference (WMD) and 95% confidence intervals were calculated. Exercise was associated with a significant increase in adiponectin (WMD=0.882 μg ml -1 , 95% CI, 0.271-1.493) but did not alter leptin and resistin level. Likewise, exercise intensity and change in body fat; as well as total exercise program duration, duration of the sessions, and change in body fat all significantly influenced the effect of exercise on adiponectin and leptin, respectively. Exercise seems to increase adiponectin levels in childhood obesity. Our results also suggested that exercise on its own, without the concomitant presence of changes in body composition levels, does not affect leptin levels.

Homeostasis Model Assessment-Adiponectin: the role of different types of physical exercise in obese adolescents.

PubMed

da Silveira Campos, Raquel M; Landi Masquio, Deborah C; Campos Corgosinho, Flávia; de Lima Sanches, Priscila; de Piano, Aline; Carnier, June; Leão da Silva, Patrícia; Grotti Clemente, Ana P; de Castro Ferreira Vicente, Sofia E; Oyama, Lila M; da Penha Oller do Nascimento, Claudia M; Tock, Lian; Tufik, Sergio; de Mello, Marco T; Dâmaso, Ana R

2017-06-01

Homeostasis Model Assessment-Adiponectin (HOMA-AD) is suggesting a new biomarker of insulin resistance in obese population. In this way, the purpose of this study was to investigate the effects of different kinds of exercise in the sensitive index predictor of insulin resistance. A total of 148 obese adolescents were enrolled in the program. They aged 15-19 y, with Body Mass Index (BMI) ≥P95th and were submitted to 1 year of interdisciplinary weight loss therapy, randomized in two groups, aerobic training (AT) (N.=51) and aerobic plus resistance training (N.=97). Blood samples were collected to analyze adiponectin, glucose and insulin concentrations. The insulin resistance was measured by HOMA-AD and Homeostasis Model Assessment Insulin Resistance Index (HOMA-IR). Both kinds of exercise training promoted a decrease in body mass, body mass index, fat mass, visceral and subcutaneous fat. However, only aerobic plus resistance training was effective to reduce HOMA-AD, insulin and glucose concentration; and increase insulin sensibility and adiponectin concentration. The aerobic plus resistance training was more effective than AT alone to improve the HOMA-AD, suggesting clinical application on obesity, diabetes, atherosclerosis and metabolic syndrome control in the pediatric population.

Artemisia Extract Improves Insulin Sensitivity in Women With Gestational Diabetes Mellitus by Up-Regulating Adiponectin.

PubMed

Sun, Xia; Sun, Hong; Zhang, Jing; Ji, Xianghong

2016-12-01

Gestational diabetes mellitus (GDM) has affected a great number of pregnant women worldwide. Artemisia extracts have been found to exhibit a potent antidiabetic effect in the treatment of type 2 diabetes mellitus. We aimed to examine the effects of Artemisia extract on insulin resistance and lipid profiles in pregnant GDM patients. Patients in their second trimester were randomly assigned to the Artemisia extract group (AE) or to a placebo group (PO). They were instructed to consume either AE or PO daily for a period of 10 weeks. Glucose and insulin profiles and adiponectin level were assessed at baseline (week 0) and after the treatment (week 10). Compared to the PO group, fasting plasma glucose, serum insulin levels, homeostasis model of assessment of insulin resistance (HOMA-IR), and β-cell function (HOMA-B) were significantly reduced in the AE group participants. Moreover, levels of circulating adiponectin were also significantly up-regulated in the AE group, which also positively contributed to improved insulin sensitivity. Daily administration of Artemisia extract improves insulin sensitivity by up-regulating adiponectin in women with gestational diabetes mellitus. © 2016, The American College of Clinical Pharmacology.

Novel adiponectin-resistin (AR) and insulin resistance (IRAR) indexes are useful integrated diagnostic biomarkers for insulin resistance, type 2 diabetes and metabolic syndrome: a case control study

PubMed Central

2011-01-01

Background Adiponectin and resistin are adipokines which modulate insulin action, energy, glucose and lipid homeostasis. Meta-analyses showed that hypoadiponectinemia and hyperresistinemia are strongly associated with increased risk of insulin resistance, type 2 diabetes (T2DM), metabolic syndrome (MS) and cardiovascular disease. The aim of this study was to propose a novel adiponectin-resistin (AR) index by taking into account both adiponectin and resistin levels to povide a better indicator of the metabolic homeostasis and metabolic disorders. In addition, a novel insulin resistance (IRAR) index was proposed by integration of the AR index into an existing insulin resistance index to provide an improved diagnostic biomarker of insulin sensitivity. Methods In this case control study, anthropometric clinical and metabolic parameters including fasting serum total adiponectin and resistin levels were determined in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS) whose ages ranged between 40-70 years old. Significant differences in continuous variables among subject groups were confirmed by ANCOVA or MANCOVA test using 1,000 stratified bootstrap samples with bias corrected and accelerated (BCa) 95% CI. Spearman's rho rank correlation test was used to test the correlation between two variables. Results The AR index was formulated as 1+log10(R0)-log10(A0). The AR index was more strongly associated with increased risk of T2DM and MS than hypoadiponectinemia and hyperresistinemia alone. The AR index was more strongly correlated with the insulin resistance indexes and key metabolic endpoints of T2DM and MS than adiponectin and resistin levels alone. The AR index was also correlated with a higher number of MS components than adiponectin and resistin levels alone. The IRAR index was formulated as log10(I0G0)+log10(I0G0)log10(R0/A0). The normal reference range of the IRAR index for insulin sensitive individuals was between 3.265 and 3.538. The minimum cut-off values of the IRAR index for insulin resistance assessment were between 3.538 and 3.955. Conclusions The novel AR and IRAR indexes are cost-effective, precise, reproducible and reliable integrated diagnostic biomarkers of insulin sensitivity for screening subjects with increased risk of future development of T2DM and MS. PMID:21251282

Comprehensive analysis of circulating adipokines and hsCRP association with cardiovascular disease risk factors and metabolic syndrome in Arabs.

PubMed

Abu-Farha, Mohamed; Behbehani, Kazem; Elkum, Naser

2014-04-09

Cardiovascular diseases (CVD) are a leading cause of death worldwide including the Middle East. This is caused in part by the dysregulation of adipose tissue leading to increased production of pro-inflammatory adipokines and reduction in cardio-protective adipokines such as adiponectin. Ethnicity has been recognized as a major factor in the association between CVD risk factors and the different circulating adipokines. In this study, for the first time, the relationship between traditional cardiovascular risk factors, Metabolic Syndrome (MetS) and circulating level of adipokines in Arab ethnicity was investigated. We conducted a population-based cross-sectional survey on 379 adult Arab participants living in Kuwait. Traditional cardiovascular risk factors such as blood pressure (BP), low density lipoprotein (LDL) and triglyceride (TG) were measured. Plasma levels of circulating Leptin, Plasminogen Activator Inhibitor (PAI-1) visfatin, adiponectin, resistin and adipsin were assessed using the multiplexing immunobead-based assay. Circulating levels of High sensitivity C-Reactive Protein (hsCRP), Leptin, PAI-1 and adiponectin were significantly higher in Arab women than men (p < 0.0001). In multi-variate analysis, the homeostasis model assessment-insulin resistance (HOMA-IR) and body mass index (BMI) showed strong association with most of the biomarkers (p < 0.05). HsCRP showed significant association with all risk factors (p < 0.05). Leptin, PAI-1 and adipsin showed significant positive correlation with BMI, unlike adiponectin which showed inverse correlation (p < 0.05). Subjects in the highest tertile of leptin, PAI-1 and hsCRP had higher odds of having Metabolic Syndrome (MetS) (odd ratio [OR] = 3.02, 95% confidence interval [CI] = 1.47-6.19) and (OR = 2.52, 95% CI = 1.45-4.35), (OR = 4.26, 95% CI = 2.39-7.59) respectively. On the other hand subjects with highest tertile of adiponectin had lower odds of having MetS (OR = 0.22, 95% CI = 0.12-0.40). Leptin, PAI-1 and hsCRP showed significant positive association with increased MetS components (P-trend <0.05), while adiponectin was negatively associated with increased MetS components (P-trend <0.0001). Our results show positive association between hsCRP, leptin, PAI-1 with increased MetS components and increase the odds of having MetS. Adiponectin on the other hand showed inverse correlation with MetS components and associated with reduction in MetS. Overall, our data highlights the significant clinical value these markers have in MetS especially hsCRP which can be used as good marker of low grade inflammation in Arabs.

Soluble CD163, adiponectin, C-reactive protein and progression of dysglycaemia in individuals at high risk of type 2 diabetes mellitus: the ADDITION-PRO cohort.

PubMed

Deichgræber, Pia; Witte, Daniel R; Møller, Holger J; Skriver, Mette V; Richelsen, Bjørn; Jørgensen, Marit E; Johansen, Nanna B; Sandbæk, Annelli

2016-11-01

Our aim was to investigate the association between the macrophage-activation marker soluble CD163 (sCD163), adiponectin, C-reactive protein (CRP) and changes in glycaemia, insulin resistance and insulin secretion in individuals at high risk of type 2 diabetes mellitus. This prospective study included 1014 individuals at high risk of type 2 diabetes mellitus participating in the Danish arm of the Anglo-Danish-Dutch study of Intensive Treatment In PeOple with ScreeN-detected Diabetes in Primary Care (ADDITION-Europe trial) baseline examination in 2001-2006 and follow-up examination (ADDITION-Progression [ADDITION-PRO]) in 2009-2011. Baseline serum samples were analysed for sCD163, adiponectin and CRP. The associations between sCD163, adiponectin and CRP per doubling of concentration, and changes per year in HbA1c, fasting plasma glucose, 2 h glucose, fasting insulin, HOMA-IR and HOMA-β were assessed using a mixed-effects model. A doubling of sCD163 concentration was positively associated with changes in HOMA-β (β = 1.160 per year, 95% CI 0.345, 1.975) as well as a doubling of CRP concentration (β = 0.410 per year, 95% CI 0.051, 0.769) after adjustment for age and sex. A doubling of adiponectin was inversely associated with changes in 2 h glucose (β =-0.063 per year, 95% CI -0.111, -0.014), HOMA-IR (β =-0.038 per year, 95% CI -0.060, -0.015) and HOMA-β (β =-1.028 per year, 95% CI -1.635, -0.421) after adjustment for age and sex. The associations were robust to adjustment for baseline waist circumference and smoking. Adjustment for CRP did not change the associations for sCD163 or adiponectin. Our findings indicate that mechanisms related to inflammation, including macrophage activation and adipocyte metabolism, may play a role in changes in glucose homeostasis in individuals at high risk of type 2 diabetes mellitus.

Analysis of the association of leptin and adiponectin concentrations with metabolic syndrome in children: Results from the IDEFICS study.

PubMed

Nappo, A; González-Gil, E M; Ahrens, W; Bammann, K; Michels, N; Moreno, L A; Kourides, Y; Iacoviello, L; Mårild, S; Fraterman, A; Molnàr, D; Veidebaum, T; Siani, A; Russo, P

2017-06-01

Adipokines may play a role in the pathogenesis of the metabolic syndrome (MetS) in children. We aimed to evaluate the association of leptin, adiponectin, and its ratio (L/A ratio) with the metabolic syndrome (MetS) in a subsample of the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS) cohort. Leptin, adiponectin and MetS parameters were measured in a subsample of 1253 children (3-9.9 years) participating to the IDEFICS study, grouped as: Non-OW (underweight/normal weight) and OW/Ob (overweight/obese). MetS was defined using the sex- and age-specific cut-offs based on the distribution of MetS components in the IDEFICS cohort. The prevalence of the MetS among OW/Ob was 24.8% and 27.1% in boys and girls respectively, whereas ≤2% among Non-OW. OW/Ob had significantly higher leptin and L/A ratio as compared to Non-OW. Significantly higher leptin was found in OW/Ob with MetS as compared with OW/Ob without MetS. Significantly lower adiponectin was observed only in OW/Ob girls as compared to Non-OW. A 1SD increase in leptin and L/A ratio z-scores or a 1SD decrease in adiponectin z-score were significantly associated with higher risk of MetS. After adjustment for BMI or body fat mass (BFM) the association remained significant only for leptin. We showed that in European children, higher leptin concentration is associated with MetS, even after adjusting for BMI or BFM, confirming an early role of leptin in MetS, while the association of adiponectin with MetS seems be mediated by body fat in this age range. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

The role of free fatty acids in the inflammatory and cardiometabolic profile in adolescents with metabolic syndrome engaged in interdisciplinary therapy.

PubMed

Masquio, Deborah Cristina Landi; de Piano-Ganen, Aline; Oyama, Lila Missae; Campos, Raquel Munhoz da Silveira; Santamarina, Aline Boveto; de Souza, Gabriel Inácio de Morais Honorato; Gomes, Aline Dal'Olio; Moreira, Renata Guimarães; Corgosinho, Flávia Campos; do Nascimento, Claudia Maria Oller; Tock, Lian; Tufik, Sergio; de Mello, Marco Túlio; Dâmaso, Ana R

2016-07-01

The purpose of the present study was to evaluate if interdisciplinary therapy can influence the cardiometabolic and serum free fatty acid profile. The second aim was to evaluate if there is an association between serum free fatty acids, inflammation and cardiometabolic biomarkers in obese adolescents with and without metabolic syndrome submitted to a long-term interdisciplinary therapy. The study involved 108 postpuberty obese adolescents, who were divided according to metabolic syndrome (MetS) diagnosis: MetS (n=32) and Non-MetS (n=76). The interdisciplinary therapy consisted of a 1-year period of nutrition, psychology, physical exercise and clinical support. After therapy, both groups improved metabolic, inflammatory (leptin, adiponectin, leptin/adiponectin ratio, adiponectin/leptin ratio and C-reactive protein) and cardiometabolic profile (PAI-1 and ICAM). Metabolic syndrome prevalence reduced from 28.70% to 12.96%. Both groups reduced myristic acid (C14:0) and increased docosahexaenoic acid (DHA, C22:6n3), heneicosapentaenoic acid (HPA, C21:5n3) and arachidonic acid (C20:4n6). After adjustment for metabolic syndrome and the number of metabolic syndrome parameters, multiple regression analysis showed that changes in VCAM and PAI-1 were negatively associated with changes in cis-linoleic acid (C18:2n6c). Additionally, changes in trans-linoleic acid (C18:2n6t) were also positively associated with these biomarkers. Moreover, leptin and leptin/adiponectin ratio were negatively associated with changes in docosapentaenoic acid (DPA, C22:5n3) and stearidonic acid (SDA, C18:4n3). Adiponectin/leptin ratio was positively associated with docosapentaenoic acid (DPA, C22:5n3). Changes in adiponectin were positively correlated with changes in omega 3, such as heneicosapentaenoic acid (HPA, C21:5n3) and docosapentaenoic acid (DPA, C22:5n3). Results support that interdisciplinary therapy can control inflammatory and cardiometabolic profile in obese adolescents. Moreover, serum fatty acids can be influenced by lifestyle changes and are able to modulate these biomarkers. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Tomato and Soy on Serum Adipokine Concentrations in Postmenopausal Women at Increased Breast Cancer Risk: A Cross-Over Dietary Intervention Trial

PubMed Central

Llanos, Adana A.; Peng, Juan; Pennell, Michael L.; Krok, Jessica L.; Vitolins, Mara Z.; Degraffinreid, Cecilia R.

2014-01-01

Context: Breast cancer risk among postmenopausal women increases as body mass index increases. Practical preventive methods to reduce risk of breast cancer are lacking. Few studies have investigated the effects of carotenoids and isoflavones on circulating adipokines in postmenopausal women. Objective: The aim was to examine the effects of lycopene- and isoflavone-rich diets on serum adipokines. Design: This was a 26-week, two-arm, longitudinal crossover trial. Setting: Participants were recruited from clinics at The Ohio State University Comprehensive Cancer Center. Participants: Seventy postmenopausal women at increased breast cancer risk participated in the study. The mean age and body mass index of participants was 57.2 years and 30.0 kg/m2, respectively; the study was comprised of 81.4% whites. Interventions: The interventions included 10 weeks of consumption of a tomato-based diet (≥25 mg lycopene daily) and 10 weeks of consumption of a soy-based diet (≥40 g of soy protein daily), with a 2-week washout in between. Main Outcome Measures: Changes in serum adiponectin, leptin, and the adiponectin to leptin ratio were examined for each intervention through linear mixed models, with ratio estimates corresponding to postintervention adipokine concentrations relative to preintervention concentrations. Results: After the tomato intervention, among all women, adiponectin concentration increased (ratio 1.09, 95% confidence interval (CI) 1.00–1.18), with a stronger effect observed among nonobese women (ratio 1.13, 95% CI 1.02–1.25). After the soy intervention, adiponectin decreased overall (ratio 0.91, 95% CI 0.84–0.97), with a larger reduction observed among nonobese women (ratio 0.89, 95% CI 0.81–0.98). Overall, no significant changes in leptin or the adiponectin to leptin ratio were observed after either intervention. Conclusions: Increasing dietary consumption of tomato-based foods may beneficially increase serum adiponectin concentrations among postmenopausal women at increased breast cancer risk, especially those who are not obese. Additional studies are essential to confirm these effects and to elucidate the specific mechanisms that may make phytonutrients found in tomatoes practical as breast cancer chemopreventive agents. PMID:24423335

Adiponectin and the steatosis marker Chi3L1 decrease following switch to raltegravir compared to continued PI/NNRTI-based antiretroviral therapy.

PubMed

Offor, Obiageli; Utay, Netanya; Reynoso, David; Somasunderam, Anoma; Currier, Judith; Lake, Jordan

2018-01-01

People with HIV are at for metabolic syndrome (MetS) and fatty liver disease, but the role of Antiretroviral therapy (ART) is poorly understood. MetS and fatty liver disease been associated with changes in adiponectin, soluble ST2 (sST2), chitinase 3-like 1 (Chi3L1), hyaluronic acid (HA), tissue inhibitor of metalloproteinase-1 (TIMP-1), lysyl oxidase-like-2 (LOXL2) and transforming growth factor β (TGF-β) concentrations in HIV-uninfected populations. Protease (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) may contribute to these comorbidities, but the effects of switching from PI- or NNRTI to raltegravir (RAL) on these biomarkers is unknown. Cryopreserved plasma was obtained from a completed, prospective trial of HIV-infected women with central adiposity on NNRTI- or PI-based ART during which they were randomized to remain on their current ART or switch to a RAL based regimen. Biomarker concentrations were quantified using ELISA and Multiplex assays at baseline and 24 weeks after randomization. Wilcoxon-signed rank test evaluated within-group changes, Spearman and linear regression models evaluated correlations between biomarkers and clinical covariates. Participants had a median age of 43 years, CD4+ T lymphocyte count 558 cells/mm3 and BMI 32 kg/m2; 35% met criteria for MetS. At baseline, higher adiponectin levels correlated with higher Chi3L1 levels (r = 0.42, p = 0.02), as did declines after 24 weeks (r = 0.40, p = 0.03). Changes in sST2 correlated with changes in Chi3L1 (r = 0.43, p = 0.02) and adiponectin (r = 0.40, p = 0.03). Adiponectin and Chi3L1 levels decreased significantly in women switched to RAL vs continue PI/NNRTI. In women with HIV and central obesity, the hepatic steatosis/fibrosis marker Chi3L1 and adiponectin decrease in conjunction with sST2 decreases following switch to RAL. Whether switching from NNRTI/PI-based regimens to RAL can improve hepatic steatosis and dysmetabolism requires further study. Clinicaltrials.gov NCT00656175.

Meta-analyses of the Association of Sleep Apnea with Insulin Resistance, and the Effects of CPAP on HOMA-IR, Adiponectin, and Visceral Adipose Fat

PubMed Central

Iftikhar, Imran H.; Hoyos, Camilla M.; Phillips, Craig L.; Magalang, Ulysses J.

2015-01-01

Objective: We sought to conduct an updated meta-analysis of randomized controlled trials (RCTs) on the effect of continuous positive airway pressure (CPAP) on insulin resistance, as measured by homeostasis model assessment of insulin resistance (HOMA-IR), visceral abdominal fat (VAF), and adiponectin. Additionally, we performed a separate meta-analysis and meta-regression of studies on the association of insulin resistance and obstructive sleep apnea (OSA). Methods: All included studies were searched from PubMed (from conception to March 15, 2014). Data were pooled across all included RCTs as the mean difference in HOMA-IR and VAF, and as the standardized mean difference in the case of adiponectin analysis. From the included case-control studies, data on the difference of HOMA-IR between cases and controls were pooled across all studies, as the standardized mean difference (SMD). Results: There was a significant difference in HOMA-IR (−0.43 [95% CIs: −0.75 to −0.11], p = 0.008) between CPAP treated and non CPAP treated participants. However, there was no significant difference in VAF or adiponectin; (−47.93 [95% CI: −112.58 to 16.72], p = 0.14) and (−0.06 [95% CI: −0.28 to 0.15], p = 0.56), respectively. Meta-analysis of 16 case-control studies showed a pooled SMD in HOMA-IR of 0.51 (95% CI: 0.28 to 0.75), p ≤ 0.001, between cases and controls. Conclusions: The results of our meta-analyses show that CPAP has a favorable effect on insulin resistance. This effect is not associated with any significant changes in total adiponectin levels or amount of VAF. Our findings also confirm a significant association between OSA and insulin resistance. Citation: Iftikhar IH, Hoyos CM, Phillips CL, Magalang UJ. Meta-analyses of the association of sleep apnea with insulin resistance, and the effects of CPAP on HOMA-IR, adiponectin, and visceral adipose fat. J Clin Sleep Med 2015;11(4):475–485. PMID:25700870

Gemfibrozil and its combination with metformin on pleiotropic effect on IL-10 and adiponectin and anti-atherogenic treatment in insulin resistant type 2 diabetes mellitus rats.

PubMed

Sharma, Ashish Kumar; Raikwar, Sachin Kumar; Kurmi, Muneem Kumar; Srinivasan, Bharthu Parthsarthi

2013-04-01

Gemfibrozil is a PPAR-α ligand that inhibits the progression of atherosclerosis in insulin resistance type 2 diabetes mellitus (IR type 2 DM). Gemfibrozil, poor anti-hyperglycemic combined with metformin, evaluated for MMP-9, IL-10 and adiponectin beyond glycemic control. IR type 2 DM induced by administering streptozotocin (90 mg/kg, i.p.) in neonatal rat model. IR type 2 DM rats at 6-week age treated for 8 weeks with (1) gemfibrozil (140 mg/kg od) and (2) gemfibrozil (70 mg/kg bid) + metformin (60 mg/kg bid). At the end, risk parameters like MMP-9, IL-10 and adiponectin were evaluated by ELISA kits. Gemfibrozil reduced the MMP-9 levels (-25.740 %) (106.772 ± 7.201 ng/ml vs. 80.231 ± 7.023 ng/ml, P < 0.01); increased adiponectin (68.321 %) (8.781 ± 1.111 μg/ml vs. 14.782 ± 1.055 μg/ml) and IL-10 (155.687 %) (334.208 ± 26.307 pg/ml vs. 853.472 ± 23.172 pg/ml, P < 0.001), but poor glycemic control (-6.169 %) (167.5 ± 16.037 vs. 157.167 ± 3.911, P = ns), hence combined with metformin showed synergistic activity, reduced the MMP-9 levels (-16.992 %) (106.772 ± 7.201 ng/ml vs. 89.941 ± 8.636 ng/ml, P < 0.05) and increased adiponectin (39.870 %) (8.781 ± 1.111 μg/ml vs. 12.282 ± 0.782 μg/ml) and, IL-10 (80.136 %) (334.208 ± 26.307 pg/ml vs. 602.029 ± 39.668 pg/ml, P < 0.01) had good glycemic control (-28.856 %) (167.5 ± 16.037 mg/dl vs. 129.167 ± 4.214 mg/dl, P < 0.05). Gemfibrozil plus metformin decrease MMP-9, increase IL-10 and adiponectin acting as anti-atherogenic, anti-inflammatory and immunomodulatory in IR type 2 DM.

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals

PubMed Central

Tanaka, Toshiko; Morris, Andrew P.; Small, Kerrin; Isaacs, Aaron; Beekman, Marian; Coassin, Stefan; Lohman, Kurt; Qi, Lu; Kanoni, Stavroula; Pankow, James S.; Uh, Hae-Won; Wu, Ying; Bidulescu, Aurelian; Rasmussen-Torvik, Laura J.; Greenwood, Celia M. T.; Ladouceur, Martin; Grimsby, Jonna; Manning, Alisa K.; Liu, Ching-Ti; Kooner, Jaspal; Mooser, Vincent E.; Vollenweider, Peter; Kapur, Karen A.; Chambers, John; Wareham, Nicholas J.; Langenberg, Claudia; Frants, Rune; Willems-vanDijk, Ko; Oostra, Ben A.; Willems, Sara M.; Lamina, Claudia; Winkler, Thomas W.; Psaty, Bruce M.; Tracy, Russell P.; Brody, Jennifer; Chen, Ida; Viikari, Jorma; Kähönen, Mika; Pramstaller, Peter P.; Evans, David M.; St. Pourcain, Beate; Sattar, Naveed; Wood, Andrew R.; Bandinelli, Stefania; Carlson, Olga D.; Egan, Josephine M.; Böhringer, Stefan; van Heemst, Diana; Kedenko, Lyudmyla; Kristiansson, Kati; Nuotio, Marja-Liisa; Loo, Britt-Marie; Harris, Tamara; Garcia, Melissa; Kanaya, Alka; Haun, Margot; Klopp, Norman; Wichmann, H.-Erich; Deloukas, Panos; Katsareli, Efi; Couper, David J.; Duncan, Bruce B.; Kloppenburg, Margreet; Adair, Linda S.; Borja, Judith B.; Wilson, James G.; Musani, Solomon; Guo, Xiuqing; Johnson, Toby; Semple, Robert; Teslovich, Tanya M.; Allison, Matthew A.; Redline, Susan; Buxbaum, Sarah G.; Mohlke, Karen L.; Meulenbelt, Ingrid; Ballantyne, Christie M.; Dedoussis, George V.; Hu, Frank B.; Liu, Yongmei; Paulweber, Bernhard; Spector, Timothy D.; Slagboom, P. Eline; Ferrucci, Luigi; Jula, Antti; Perola, Markus; Raitakari, Olli; Florez, Jose C.; Salomaa, Veikko; Eriksson, Johan G.; Frayling, Timothy M.; Hicks, Andrew A.; Lehtimäki, Terho; Smith, George Davey; Siscovick, David S.; Kronenberg, Florian; van Duijn, Cornelia; Loos, Ruth J. F.; Waterworth, Dawn M.; Meigs, James B.; Dupuis, Josee; Richards, J. Brent

2012-01-01

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8–1.2×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10−4). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10−3, n = 22,044), increased triglycerides (p = 2.6×10−14, n = 93,440), increased waist-to-hip ratio (p = 1.8×10−5, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10−3, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10−13, n = 96,748) and decreased BMI (p = 1.4×10−4, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance. PMID:22479202

Acylated and unacylated ghrelin levels in normal weight and obese children: influence of puberty and relationship with insulin, leptin and adiponectin levels.

PubMed

Bellone, S; Prodam, F; Savastio, S; De Rienzo, F; Demarchi, I; Trovato, L; Petri, A; Rapa, A; Aimaretti, G; Bona, G

2012-02-01

Ghrelin circulates in blood as acylated (AG) and unacylated (UAG) ghrelin. The physiological role of the two forms is poorly understood, in particular in childhood. Aim of the study was to evaluate the AG and UAG levels in obese and normal weight (NW) children, pre-pubertal and pubertal, and their relationship with insulin, leptin and adiponectin levels. A population based study in which AG, UAG, leptin, adiponectin, glucose, insulin, testosterone or estradiol levels, insulinemic indexes were evaluated in 82 NW and 58 obese (OB) children. Both ghrelin forms in NW were higher (AG, p<0.02; UAG, p<0.0001) than in OB subjects, with similar ratio AG/UAG . While no differences were observed for gender, puberty AG (p<0.01) and UAG (p<0.0001) levels were higher in pre-pubertal than pubertal NW and OB subjects. Adiponectin levels in NW subjects were higher (p<0.001), while leptin and insulin levels were lower (p<0.0001) than in OB subjects. NW children showed homeostasis model assessment (HOMA) and HOMAβ indices lower than OB children (p<0.0001) with a higher a quantitative insulin sensitivity check index (p<0.0001). AG and UAG levels correlated to each other (p<0.0001), each showing a negative correlation to age, height, weight and body mass index. Both forms, but more strongly UAG, correlated with adiponectin, leptin, and insulin. OB children show lower levels of both AG and UAG when compared to NW subjects, with lower levels during puberty. These results demonstrate a peculiar strong relationship between UAG levels and metabolic parameters in the pediatric population, suggesting a role for UAG in metabolic functions.

Airway and serum adipokines after allergen and diesel exposure in a controlled human crossover study of atopic adults.

PubMed

Kramer, Marabeth M; Hirota, Jeremy A; Sood, Akshay; Teschke, Kay; Carlsten, Christopher

2017-04-01

Adipokines are mediators released from adipose tissue. These proteins are regarded as active elements of systemic and pulmonary inflammation, whose dysregulation can alter an individual's risk of developing allergic lung diseases. Despite this knowledge, adipokine responses to inhaled stimuli are poorly understood. We sought to measure serum and lung adiponectin, leptin, and resistin in an atopic adult study population following exposure to allergen and diesel exhaust (DE). Two types of lung samples including bronchoalveolar lavage (BAL) and bronchial wash (BW), and a time course of serum samples, were collected from the 18 subjects who participated in the randomized, double-blinded controlled human study. The two crossover exposure triads in this study were inhaled DE and filtered air each followed by instilled allergen or saline. Serum and lung adipokine responses to these exposures were quantified using enzyme-linked immunosorbent assay. Allergen significantly increased adiponectin and leptin in BAL, and adiponectin in the BW 48 hours after exposure. Serum leptin and resistin responses were not differentially affected by exposure, but varied over time. Coexposure with DE and allergen revealed significant correlations between the adiponectin/leptin ratio and FEV 1 changes and airway responsiveness measures. Changes in lung and serum adipokines in response to allergen exposure were identified in the context of a controlled exposure study. Coexposure identified a potentially protective role of adiponectin in the lung. This response was not observed in those with baseline airway hyper-responsiveness, or after allergen exposure alone. The clinical relevance of this potentially adaptive adipokine pattern warrants further study. Copyright © 2016 Elsevier Inc. All rights reserved.

Adiponectin and Adiponectin Receptor Gene Variants in Relation to Type 2 Diabetes and Insulin Resistance-Related Phenotypes

PubMed Central

Potapov, Viktor A.; Chistiakov, Dimitry A.; Dubinina, Anna; Shamkhalova, Minara S.; Shestakova, Marina V.; Nosikov, Valery V.

2008-01-01

BACKGROUND: Alterations in adiponectin-mediated pathways are known to be associated with glucose intolerance, insulin resistance (IR), obesity, and type 2 diabetes (T2D) mellitus. Genetic variations in adiponectin (ADIPOQ) and adiponectin 1 and 2 receptor (ADIPOR1 and ADIPOR2) could have effects on IR-related phenotypes and T2D. Here we examine whether the polymorphic markers rs2241766 (ADIPOQ), rs22753738 (ADIPOR1), rs11061971 and rs16928751 (both in ADIPOR2) are implicated in susceptibility to T2D in a Russian population. METHODS: The polymorphic markers were genotyped in 129 T2D patients, and 117 non-diabetic controls, by polymerase chain reaction (PCR) restriction fragment length polymorphism approach. In the subjects, biochemical characteristics including serum insulin, plasma glucose and serum lipids/lipoproteins were measured and compared for correlation with the genetic variations studied. RESULTS: Allele T of rs11061971 and allele A of rs16928751 showed association with higher risk of diabetes providing odds ratios (OR) of 2.05 (p = 0.0025) and 1.88 (p = 0.018), respectively. Haplotype A-G consisting of allele A of rs11061971 and allele G of rs16928751 was associated with reduced risk of T2D (OR = 0.59, pc = 0.0224). Compared to other variants, diabetic patients double homozygous for A/A of rs16928751 and G/G of rs16928751 had decreased homeostasis model assessment-insulin resistance (pc = 0.0375) and serum triglycerides (pc = 0.0285). CONCLUSIONS: The variants of ADIPOR2 confer susceptibility to T2D and are associated with some IR-related phenotypes in the Russian study population. PMID:18548168

Circulating adiponectin concentrations are increased by dietary resistant starch and correlate with serum 25-hydroxycholecalciferol concentrations and kidney function in Zucker diabetic fatty rats.

PubMed

Koh, Gar Yee; Derscheid, Rachel; Fuller, Kelly N Z; Valentine, Rudy J; Leow, Shu En; Reed, Leah; Wisecup, Emily; Schalinske, Kevin L; Rowling, Matthew J

2016-04-01

We previously reported that dietary resistant starch (RS) type 2 prevented proteinuria and promoted vitamin D balance in type 2 diabetic (T2D) rats. Here, our primary objective was to identify potential mechanisms that could explain our earlier observations. We hypothesized that RS could promote adiponectin secretion and regulate the renin-angiotensin system activity in the kidney. Lean Zucker rats (n = 5) were fed control diet; Zucker diabetic fatty rats (n = 5/group) were fed either an AIN-93G control diet (DC) or AIN-93G diet containing either 10% RS or 20% RS (HRS) for 6 weeks. Resistant starch had no impact on blood glucose concentrations and hemoglobin A1c percentage, yet circulating adiponectin was 77% higher in HRS-fed rats, compared to DC rats. Adiponectin concentrations strongly correlated with serum 25-hydroxycholecalciferol (r = 0.815; P < .001) and urinary creatinine concentrations (r = 0.818; P < .001) and inversely correlated with proteinuria (r = -0.583; P = .02). Serum angiotensin II concentrations were 44% lower, and expression of the angiotensin II receptor, type 1, was attenuated in RS-fed rats. Moreover, we observed a 14-fold increase in messenger RNA expression of nephrin, which is required for functioning of the renal filtration barrier, in HRS rats. The HRS, but not 10% RS diet, increased circulating 25-hydroxycholecalciferol concentrations and attenuated urinary loss of vitamin D metabolites in Zucker diabetic fatty rats. Taken together, we provide evidence that vitamin D balance in the presence of hyperglycemia is strongly associated with serum adiponectin levels and reduced renal renin-angiotensin system signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

Adiposity associated changes in serum glucose and adiponectin levels modulate ovarian steroidogenesis during delayed embryonic development in the fruit bat, Cynopterus sphinx.

PubMed

Anuradha; Krishna, Amitabh

2018-06-01

The aim of the present study was to evaluate the mechanism by which embryonic development in Cynopterus sphinx is impaired during the period of increased accumulation of white adipose tissue during winter scarcity of food. The change in the mass of white adipose tissue during adipogenesis showed significant positive correlation with the circulating glucose level. But increase in circulating glucose level during the adipogenesis showed negative correlation with circulating progesterone and adiponectin levels. The in vivo study showed increased glucose uptake by the adipose tissue during adipogenesis due to increased expression of insulin receptor (IR) and glucose transporter (GLUT) 4 proteins. This study showed decline in the adiponectin level during fat accumulation. In the in vitro study, ovary treated with high doses of glucose showed impaired progesterone synthesis. This is due to decreased glucose uptake mediated decrease in the expression of luteinizing hormone-receptor, steroidogenic acute regulatory protein, IR, GLUT4 and AdipoR1 proteins. But the ovary treated with adiponectin either alone or with higher concentration of glucose showed improvement in progesterone synthesis due to increased expression of IR, GLUT4 and AdipoR1 mediated increased glucose uptake. In conclusion, increased circulating glucose level prior to winter dormancy preferably transported to white adipose tissue for fat accumulation diverting glucose away from the ovary. Consequently the decreased availability of adiponectin and glucose to the ovary and utero-embryonic unit may be responsible for impaired progesterone synthesis and delayed embryonic development. The delayed embryonic development in Cynopterus sphinx may have evolved, in part, as a mechanism to prevent pregnancy loss during the period of decreased energy availability. Copyright © 2018 Elsevier Inc. All rights reserved.

Adiposity and insulin resistance correlate with telomere length in middle-aged Arabs: the influence of circulating adiponectin.

PubMed

Al-Attas, Omar S; Al-Daghri, Nasser M; Alokail, Majed S; Alfadda, Assim; Bamakhramah, Ahmed; Sabico, Shaun; Pritlove, Dave; Harte, Alison; Tripathi, Gyanendra; McTernan, Philip G; Kumar, Sudhesh; Chrousos, George

2010-10-01

Studies in obesity have implicated adipocytokines in the development of insulin resistance, which in turn may lead to accelerated aging. In this study, we determined associations of chromosomal telomere length (TL) to markers of obesity and insulin resistance in middle-aged adult male and female Arabs with and without diabetes mellitus type 2 (DMT2). One hundred and ninety-three non-diabetic and DMT2 subjects without complications (97 males and 96 females) participated in this cross-sectional study. Clinical data, as well as fasting blood samples, were collected. Serum glucose and lipid profile were determined using routine laboratory methods. Serum insulin, leptin, adiponectin, resistin, tumor necrosis factor-α, and PAI-1 were quantified using customized multiplex assay kits. High sensitive C-reactive protein (hsCRP) and angiotensin II (ANG II) were measured using ELISAs. Circulating leukocyte TL was examined by quantitative real-time PCR. Circulating chromosomal leukocyte TL had significant inverse associations with body mass index (BMI), systolic blood pressure, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein (LDL)- and total cholesterol, ANG II and hsCRP levels. Adiponectin, BMI, systolic blood pressure, and LDL cholesterol predicted 47% of the variance in TL (P<0.0001). HOMA-IR was the most significant predictor for TL in males, explaining 35% of the variance (P=0.01). In females, adiponectin accounted for 28% of the variance in TL (P=0.01). Obesity and insulin resistance are associated with chromosomal TL among adult Arabs. Evidence of causal relations needs further investigation. The positive association of adiponectin to TL has clinical implications as to the possible protective effects of this hormone from accelerated aging.