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Sample records for adiponectin levels increased

  1. Higher Circulating Adiponectin Levels Are Associated with Increased Risk of Atrial Fibrillation in Older Adults

    PubMed Central

    Macheret, Fima; Bartz, Traci M.; Djousse, Luc; Ix, Joachim H.; Mukamal, Kenneth J.; Zieman, Susan J.; Siscovick, David S.; Tracy, Russell P.; Heckbert, Susan R.; Psaty, Bruce M.; Kizer, Jorge R.

    2016-01-01

    Background Adiponectin has cardioprotective properties, suggesting that lower levels seen in obesity and diabetes could heighten risk of atrial fibrillation (AF). Among older adults, however, higher adiponectin has been linked to greater incidence of adverse outcomes associated with AF, although recent reports have shown this association to be U-shaped. We postulated that higher adiponectin would be linked to increased risk for AF in older adults in a U-shaped manner. Methods We examined the associations of total and high-molecular-weight (HMW) adiponectin with incident AF among individuals free of prevalent cardiovascular disease (CVD) participating in a population-based cohort study of older adults (n=3190; age=74±5 years). Results During median follow-up of 11.4 years, there were 886 incident AF events. Adjusted cubic splines showed a positive and linear association between adiponectin and incident AF. After adjusting for potential confounders, including amino-terminal pro-B-type natriuretic peptide 1–76, the hazard ratio (95% CI) for AF per SD increase in total adiponectin was 1.14 (1.05–1.24), while that for HMW adiponectin was 1.17 (1.08–1.27). Additional adjustment for putative mediators, including subclinical CVD, diabetes, lipids, and inflammation, did not significantly affect these estimates. Conclusions The present findings demonstrate that higher, not lower, levels of adiponectin are independently associated with increased risk of AF in older adults despite its documented cardiometabolic benefits. Additional work is necessary to determine if adiponectin is a marker of failed counter-regulatory pathways or whether this hormone is directly harmful in the setting of or as a result of advanced age. PMID:25855796

  2. Adiponectin plasma levels are increased by atorvastatin treatment in subjects at high cardiovascular risk.

    PubMed

    Blanco-Colio, Luis M; Martín-Ventura, Jose L; Gómez-Guerrero, Carmen; Masramon, Xavier; de Teresa, Eduardo; Farsang, Csaba; Gaw, Allan; Gensini, GianFranco; Leiter, Lawrence A; Langer, Anatoly; Egido, Jesús

    2008-05-31

    Adiponectin can suppress atherogenesis by inhibiting the adherence of monocytes, reducing their phagocytic activity, and suppressing the accumulation of modified lipoproteins in the vascular wall. Contradictory data have been reported about the effect of statins on adiponectin plasma levels. In this work, adiponectin plasma levels were measured in 102 statin-free subjects from the Spanish population of the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study, a 12-week, prospective, multi-centre, open-label trial which enrolled subjects with coronary heart disease, coronary heart disease-equivalent or a 10-year coronary heart disease risk >20%. Subjects were assigned to atorvastatin (10-80 mg/day) based on low-density lipoprotein (LDL)-cholesterol concentration at screening. For comparison, age and gender-matched blood donors (N=40) were used as controls. Control subjects did not present hypertension, hypercholesterolemia, diabetes, metabolic syndrome and history of cardiovascular diseases. Adiponectin levels were diminished in patients at high cardiovascular risk compared with control subjects [4166 (3661-4740) vs 5806 (4764-7075) ng/ml respectively; geometric mean (95% CI); P<0.0001]. In the whole population, atorvastatin treatment increased adiponectin levels [9.7 (3.2-16.7);% Change (95% CI); P=0.003]. This increment was in a dose-dependent manner; maximal effect observed with atorvastatin 80 mg/d [24.7 (5.7-47.1); P=0.01]. Adiponectin concentrations were positively correlated with high-density lipoprotein-cholesterol both before and after atorvastatin treatment. No association was observed between adiponectin and LDL-cholesterol before and after atorvastatin treatment. In conclusion, atorvastatin increased adiponectin plasma levels in subjects at high cardiovascular risk, revealing a novel anti-inflammatory effect of this drug.

  3. Adiposity distribution influences circulating adiponectin levels.

    PubMed

    Guenther, Mitchell; James, Roland; Marks, Jacqueline; Zhao, Shi; Szabo, Aniko; Kidambi, Srividya

    2014-10-01

    Thirty percent of obese individuals are metabolically healthy and were noted to have increased peripheral obesity. Adipose tissue is the primary source of adiponectin, an adipokine with insulin-sensitizing and anti-inflammatory properties. Lower adiponectin levels are observed in individuals with obesity and those at risk for cardiovascular disease. Conversely, higher levels are noted in some obese individuals who are metabolically healthy. Our objective was to determine whether abdominal adiposity distribution, rather than body mass index (BMI) status, influences plasma adiponectin level. A total of 424 subjects (female, 255) of Northern European ancestry were recruited from "Take Off Pounds Sensibly" weight loss club members. Demographics, anthropometrics, and dual-emission x-ray absorptiometry of the whole body, and computed tomography scan of the abdomen were performed to obtain total body fat content and to quantify subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), respectively. Laboratory measurements included fasting plasma glucose, insulin, lipid panel, and adiponectin. Age- and gender-adjusted correlation analyses showed that adiponectin levels were negatively correlated with BMI, waist circumference, triglycerides, total fat mass, and VAT. A positive correlation was noted with high-density lipoprotein cholesterol and fat-free mass (P < 0.05). SAT-to-VAT ratios were also significantly associated with adiponectin (r = 0.13, P = 0.001). Further, the best positive predictors for plasma adiponectin were found to be SAT-to-VAT ratios and gender by regression analyses (P < 0.01). Abdominal adiposity distribution is an important predictor of plasma adiponectin and obese individuals with higher SAT-to-VAT ratios may have higher adiponectin levels.

  4. Weight loss increased serum adiponectin but decreased lipid levels in obese subjects whose body mass index was lower than 30 kg/m².

    PubMed

    Lang, Hui-Fen; Chou, Ching-Ya; Sheu, Wanye Huey-Herng; Lin, Jin-Yuarn

    2011-05-01

    We hypothesized that weight loss in obese subjects may affect adipokine levels, such as adiponectin and tumor necrosis factor (TNF) α. This study investigated the effects of an 8-week weight-control program on serum adiponectin, TNF-α, and blood lipid level profiles in obese subjects. Twenty obese subjects with a body mass index (BMI) higher than 25 kg/m² were recruited for this weight loss program that used dietetic control and aerobic exercise training. A total of 3 obese men and 11 obese women (mean age, 40.3 ± 10.8 years; BMI, 30.0 ± 3.4 kg/m²) finished the program. Anthropometric and biochemical characteristics in subjects before and after the program were determined. The results showed that subjects' body weight, BMI, waist circumference, hip circumference, diastolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol levels significantly (P < .05) decreased during the program. Further analysis showed a negative correlation between delta adiponectin and delta TNF-α, triacylglycerol, and systolic blood pressure in obese subjects. Subgroup analysis showed that obese subjects whose original BMI was less than 30 kg/m² had significantly increased serum adiponectin levels, and more than 3% weight reduction markedly improved blood lipids and body fat profiles during the program. Our findings suggest that weight reduction through an 8-week weight loss program may have anti-inflammatory and antiatherogenic effects via increased serum adiponectin levels and improvements in blood lipid profiles and systolic blood pressure.

  5. Effect of diet on adiponectin levels in blood.

    PubMed

    Silva, Flávia M; de Almeida, Jussara C; Feoli, Ana M

    2011-10-01

    Dietary management has been considered an alternative means of modulating adiponectin levels. The purpose of this review is to examine the scientific evidence regarding the effect of diet on adiponectin levels in blood. Clinical trials were selected from Medline until April 2010 using the following MeSH terms: adipokines OR adiponectin AND diet OR lifestyle. A total of 220 articles were identified in the initial search, and 52 studies utilizing three different methods of dietary management were included in the present review: low-calorie diets (n = 9 studies), modification of diet composition (n = 33), and diet plus exercise (n = 10). Daily intake of fish or omega-3 supplementation increased adiponectin levels by 14-60%. Weight loss achieved with a low-calorie diet plus exercise increased adiponectin levels in the range of 18-48%. A 60-115% increase in adiponectin levels was obtained with fiber supplementation. In conclusion, dietary management can be an effective therapeutic means of increasing adiponectin levels. Studies investigating different forms of adiponectin and changes in the types of adipose tissue are necessary in order to elucidate the mechanisms involved in the modulation of adiponectin levels.

  6. Enhanced Metabolic Flexibility Associated with Elevated Adiponectin Levels

    PubMed Central

    Asterholm, Ingrid Wernstedt; Scherer, Philipp E.

    2010-01-01

    Metabolically healthy individuals effectively adapt to changes in nutritional state. Here, we focus on the effects of the adipocyte-derived secretory molecule adiponectin on adipose tissue in mouse models with genetically altered adiponectin levels. We found that higher adiponectin levels increased sensitivity to the lipolytic effects of adrenergic receptor agonists. In parallel, adiponectin-overexpressing mice also display enhanced clearance of circulating fatty acids and increased expansion of subcutaneous adipose tissue with chronic high fat diet (HFD) feeding. These adaptive changes to the HFD were associated with increased mitochondrial density in adipocytes, smaller adipocyte size, and a general transcriptional up-regulation of factors involved in lipid storage through efficient esterification of free fatty acids. The physiological response to adiponectin overexpression resembles in many ways the effects of chronic exposure to β3-adrenergic agonist treatment, which also results in improvements in insulin sensitivity. In addition, using a novel computed tomography-based method for measurements of hepatic lipids, we resolved the temporal events taking place in the liver in response to acute HFD exposure in both wild-type and adiponectin-overexpressing mice. Increased levels of adiponectin potently protect against HFD-induced hepatic lipid accumulation and preserve insulin sensitivity. Given these profound effects of adiponectin, we propose that adiponectin is a factor that increases the metabolic flexibility of adipose tissue, enhancing its ability to maintain proper function under metabolically challenging conditions. PMID:20093494

  7. 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

    2017-01-13

    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 MnCl2) 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.

  8. LDL but not HDL increases adiponectin release of primary human adipocytes.

    PubMed

    Krautbauer, Sabrina; Neumeier, Markus; Eisinger, Kristina; Hader, Yvonne; Dada, Ashraf; Schmitz, Gerd; Aslanidis, Charalampos; Buechler, Christa

    2013-12-01

    Adipocytes in obesity have inappropriately low cholesterol while adiponectin release is reduced. Cholesterol shortage may contribute to low adiponectin and 3T3-L1 cells treated with lovastatin have diminished adiponectin in cell supernatants. LDL and HDL deliver cholesterol to adipocytes. LDL but not HDL increases adiponectin in cell supernatants of primary human adipocytes. The effect of LDL is not blocked by receptor associated protein suggesting that members of the LDL-receptor family are not involved. To evaluate whether these in vitro observations translate into changes in systemic adiponectin, adiponectin was measured in serum of three patients before, immediately after and 3d after LDL-apheresis. Whereas circulating lipoproteins are reduced immediately after apheresis adiponectin is not changed. Therefore, acute lowering of lipoproteins does not affect systemic adiponectin also excluding that plenty of adiponectin is bound to lipoprotein particles. Accordingly, levels of adiponectin in purified lipoproteins are quite low. Familial hypobetalipoproteinemia (FHBL) is a rare disorder associated with low plasma LDL. Serum adiponectin is, however, similar compared to healthy controls. Thus, neither LDL nor HDL directly contributes to circulating adiponectin concentrations.

  9. Caloric restriction increases adiponectin expression by adipose tissue and prevents the inhibitory effect of insulin on circulating adiponectin in rats.

    PubMed

    Ding, Qi; Ash, Catherine; Mracek, Tomas; Merry, Brian; Bing, Chen

    2012-08-01

    Aging is associated with redistribution of body fat and the development of insulin resistance. White adipose tissue emerges as an important organ in controlling life span. Caloric restriction (CR) delays the rate of aging possibly modulated partly by altering the amount and function of adipose tissue. Adiponectin is a major adipose-derived adipokine that has anti-inflammatory and insulin-sensitizing properties. This study examined the effects of CR on adiposity and gene expression of adiponectin, its receptors (AdipoR1 and AdipoR2) in adipose tissue and in isolated adipocytes of Brown Norway rats that had undergone CR for 4 months or fed ad libitum. The study also determined plasma concentrations of adiponectin and insulin in these animals and whether insulin infusion for 7 days affects adiponectin expression and its circulating concentrations under CR conditions. CR markedly reduced body weight as anticipated, epididymal fat mass and adipocyte size. CR led to an increase in plasma free fatty acid and glycerol (both twofold), and adipose triglyceride lipase messenger RNA (mRNA) in adipose tissue and isolated adipocytes (both >2-fold). Adiponectin mRNA levels were elevated in adipose tissue and adipocytes (both >2-fold) as was plasma adiponectin concentration (2.8-fold) in CR rats. However, CR did not alter tissue or cellular AdipoR1 and AdipoR2 expression. Seven days of insulin infusion decreased adiponectin mRNA in adipose tissue but did not reverse the CR-induced up-regulation of circulating adiponectin levels. Our results suggest that the benefits of CR could be, at least in part, dependent on enhanced expression and secretion of adiponectin by adipocytes.

  10. 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

  11. Adiponectin increases glucose-induced insulin secretion through the activation of lipid oxidation.

    PubMed

    Patané, G; Caporarello, N; Marchetti, P; Parrino, C; Sudano, D; Marselli, L; Vigneri, R; Frittitta, L

    2013-12-01

    The expression of adiponectin receptors has been demonstrated in human and rat pancreatic beta cells, where globular (g) adiponectin rescues rat beta cells from cytokine and fatty acid-induced apoptosis. The aim of our study was to evaluate whether adiponectin has a direct effect on insulin secretion and the metabolic pathways involved. Purified human pancreatic islets and rat beta cells (INS-1E) were exposed (1 h) to g-adiponectin, and glucose-induced insulin secretion was measured. A significant increase in glucose-induced insulin secretion was observed in the presence of g-adiponectin (1 nmol/l) with respect to control cells in both human pancreatic islets (n = 5, p < 0.05) and INS-1E cells (n = 5, p < 0.001). The effect of globular adiponectin on insulin secretion was independent of AMP-dependent protein kinase (AMPK) activation or glucose oxidation. In contrast, g-adiponectin significantly increased oleate oxidation (n = 5, p < 0.05), and the effect of g-adiponectin (p < 0.001) on insulin secretion by INS-1E was significantly reduced in the presence of etomoxir (1 μmol/l), an inhibitor of fatty acid beta oxidation. g-Adiponectin potentiates glucose-induced insulin secretion in both human pancreatic islets and rat beta cells via an AMPK independent pathway. Increased fatty acid oxidation rather than augmented glucose oxidation is the mechanism responsible. Overall, our data indicate that, in addition to its anti-apoptotic action, g-adiponectin has another direct effect on beta cells by potentiating insulin secretion. Adiponectin, therefore, in addition to its well-known effect on insulin sensitivity, has important effects at the pancreatic level.

  12. Plasma adiponectin levels are increased despite insulin resistance in corticotropin-releasing hormone transgenic mice, an animal model of Cushing syndrome.

    PubMed

    Shinahara, Masayuki; Nishiyama, Mitsuru; Iwasaki, Yasumasa; Nakayama, Shuichi; Noguchi, Toru; Kambayashi, Machiko; Okada, Yasushi; Tsuda, Masayuki; Stenzel-Poore, Mary P; Hashimoto, Kozo; Terada, Yoshio

    2009-01-01

    Adiponectin (AdN), an adipokine derived from the adipose tissue, has an insulin-sensitizing effect, and plasma AdN is shown to be decreased in obesity and/or insulin resistant state. To clarify whether changes in AdN are also responsible for the development of glucocorticoid-induced insulin resistance, we examined AdN concentration in plasma and AdN expression in the adipose tissue, using corticotropin-releasing hormone (CRH) transgenic mouse (CRH-Tg), an animal model of Cushing syndrome. We found, unexpectedly, that plasma AdN levels in CRHTg were significantly higher than those in wild-type littermates (wild-type: 19.7+/-2.5, CRH-Tg: 32.4+/-3.1 microg/mL, p<0.01). On the other hand, AdN mRNA and protein levels were significantly decreased in the adipose tissue of CRH-Tg. Bilateral adrenalectomy in CRH-Tg eliminated both their Cushing's phenotype and their increase in plasma AdN levels (wild-type/sham: 9.4+/-0.5, CRH-Tg/sham: 15.7+/-2.0, CRH-Tg/ADX: 8.5+/-0.4 microg/mL). These results strongly suggest that AdN is not a major factor responsible for the development of insulin resistance in Cushing syndrome. Our data also suggest that glucocorticoid increases plasma AdN levels but decreases AdN expression in adipocytes, the latter being explained possibly by the decrease in AdN metabolism in the Cushing state.

  13. Novel Locus FER Is Associated With Serum HMW Adiponectin Levels

    PubMed Central

    Qi, Lu; Menzaghi, Claudia; Salvemini, Lucia; De Bonis, Concetta; Trischitta, Vincenzo; Hu, Frank B.

    2011-01-01

    OBJECTIVE High molecular weight (HMW) adiponectin is a predominant isoform of circulating adiponectin and has been related to type 2 diabetes. Previous linkage studies suggest that different genetic components might be involved in determining HMW and total adiponectin levels. RESEARCH DESIGN AND METHODS We performed a genome-wide association study (GWAS) of serum HMW adiponectin levels in individuals of European ancestry drawn from the Nurses’ Health Study (NHS) (N = 1,591). The single nucleotide polymorphisms (SNPs) identified in the GWAS analysis were replicated in an independent cohort of Europeans (N = 626). We examined the associations of the identified variations with diabetes risk and metabolic syndrome. RESULTS We identified a novel locus near the FER gene (5q21) at a genome-wide significance level, best represented by SNP rs10447248 (P = 4.69 × 10−8). We also confirmed that variations near the adiponectin-encoding ADIPOQ locus (3q27) were related to serum HMW adiponectin levels. In addition, we found that FER SNP rs10447248 was related to HDL cholesterol levels (P = 0.009); ADIPOQ variation was associated with fasting glucose (P = 0.04), HDL cholesterol (P = 0.04), and a metabolic syndrome score (P = 0.002). CONCLUSIONS Our results suggest that different loci may be involved in regulation of circulating HMW adiponectin levels and provide novel insight into the mechanisms that affect HMW adiponectin homeostasis. PMID:21700879

  14. Infliximab therapy increases body fat mass in early rheumatoid arthritis independently of changes in disease activity and levels of leptin and adiponectin: a randomised study over 21 months

    PubMed Central

    2010-01-01

    Introduction Rheumatoid arthritis (RA) is associated with changes in body composition and bone mineral density (BMD). The purpose of the present study was to evaluate whether anti-TNF treatment in early RA has an impact on body composition and BMD besides that which could be achieved by intensive disease-modifying anti-rheumatic drug (DMARD) combination therapy. Methods Forty patients with early RA who failed treatment with methotrexate up to 20 mg/week for 3 months were randomised to addition of sulphasalazine and hydroxychloroquine (treatment A) or addition of infliximab (treatment B). At 3, 12 and 24 months, body composition and BMD were assessed by total-body dual-energy X-ray absorptiometry. At the same time points, leptin, adiponectin, apolipoproteins, insulin-like growth factor-1 (IGF-1) and markers of bone remodelling were analysed. Compliance to treatment was considered in the analyses. Data were analysed with a mixed, linear model. Results Patients treated with anti-TNF had a significant increase in fat mass at 2 years, 3.8 (1.6 to 5.9) kg, in contrast to patients in treatment A, 0.4 (-1.5 to 2.2) kg (P = 0.040), despite similar reduction in disease activity. Both treatment strategies prevented loss of muscle mass and bone. Leptin concentrations increased significantly in both groups at 2 years and adiponectin increased significantly at 2 years in treatment A and at 1 year in treatment B. There were no significant changes in apolipoproteins or IGF-1. The markers of bone resorption decreased at 12 months in both treatment groups with no significant difference between the treatment groups. Conclusions Infliximab therapy increased body fat mass, an effect that was not achieved with the combination of DMARDs, despite a similar reduction in disease activity, and thus seemed to be drug specific. The increase of fat mass was not associated with an exacerbated atherogenic lipid profile. Leptin and adiponectin concentrations increased in both treatment groups. The

  15. The Effects of Aerobic Exercise on Plasma Adiponectin Level and Adiponectin-related Protein Expression in Myocardial Tissue of ApoE(-/-) Mice.

    PubMed

    Zhu, Xiao-Juan; Chen, Li-Hui; Li, Jiang-Hua

    2015-12-01

    Numerous reports have confirmed the effect of ApoE knockout in the induction of cardiovascular diseases and the protective effect of adiponectin against the progression of cardiovascular diseases. The aim of this study was to reveal the roles of adiponectin signaling in the progression of cardiovascular diseases induced by ApoE knockout and to analyze the healthy effects of aerobic exercise on ApoE knockout mice (ApoE(-/-) mice) through observing the changes of adiponectin signaling caused by ApoE knockout and aerobic exercise. A twelve-week aerobic exercise program was carried out on the male ApoE(-/-) mice and the C57BL / 6J mice (C57 mice) of the same strain. Results show that the body weights, blood lipid level, plasma adiponectin level and adiponectin-related proteins in myocardial tissue were all significantly changed by ApoE knockout. A twelve-week aerobic exercise program exerted only minimal effects on the body weights, blood lipid levels, and plasma adiponectin levels of ApoE(-/-) mice, but increased the expressions of four adiponectin-related proteins, AdipoR1, PPARα, AMPK and P-AMPK, in the myocardial tissue of the ApoE(-/-) mice. In summary, adiponectin signaling may play an import role in the progression of cardiovascular diseases induced by ApoE knockout, and the beneficial health effects of aerobic exercise on ApoE(-/-) mice may be mainly from the increased adiponectin-related protein expression in myocardial tissue. Key pointsA twelve-week aerobic exercise program exerted only limited effects on the body weights and the plasma adiponectin levels of both the normal mice and the ApoE(-/-) mice but did effectively regulate the blood lipid levels of the normal mice (but not the ApoE(-/-) mice).After 12 weeks of aerobic exercise, expression of the adiponectin-related proteins in the myocardial tissue of the ApoE(-/-) and normal mice was increased, but the increased amplitudes of these proteins in the ApoE(-/-) mice were much larger in the Apo

  16. Adiponectin concentrations increase during acute FFA elevation in humans treated with rosiglitazone.

    PubMed

    Krzyzanowska, K; Mittermayer, F; Krugluger, W; Roden, M; Schernthaner, G; Wolzt, M

    2007-10-01

    The adipocytokine adiponectin is released by adipocytes upon activation of the peroxisome proliferator-activated receptor gamma (PPAR gamma). PPAR gamma has binding sites for thiazolidinediones and free fatty acids (FFAs). To evaluate if adiponectin serum concentrations are synergistically regulated by FFAs and thiazolidinediones IN VIVO plasma FFAs were acutely elevated in healthy subjects pre-treated with rosiglitazone or placebo. Sixteen healthy male subjects (23-37 years) were included in this double-blind, randomized, placebo-controlled parallel-group study. Rosiglitazone 8 mg or placebo was administered daily for 21 days. On the last day plasma FFA concentrations were increased by an intravenous triglyceride/heparin infusion. Blood for determination of adiponectin, C-reactive protein (CRP), leptin, resistin, FFAs, glucose, and insulin was drawn at baseline and on day 21 before and after 5 hours of triglyceride/heparin infusion. Adiponectin concentrations increased and FFA levels decreased in subjects receiving rosiglitazone (all p<0.05 VS. baseline). Lipid infusion significantly increased FFA plasma concentrations, with an attenuated elevation in rosiglitazone-treated subjects. However, adiponectin concentrations were only increased in subjects on rosiglitazone (p=0.018 VS. before lipid infusion), but not in controls. Leptin increased during lipid infusion in subjects receiving placebo but not in those on rosiglitazone. CRP and resistin were not affected by rosiglitazone or FFAs. The acute increase in circulating adiponectin concentrations during acutely elevated FFA depends on PPAR gamma activation in healthy subjects.

  17. Blockade of the renin-angiotensin system increases adiponectin concentrations in patients with essential hypertension.

    PubMed

    Furuhashi, Masato; Ura, Nobuyuki; Higashiura, Katsuhiro; Murakami, Hideyuki; Tanaka, Marenao; Moniwa, Norihito; Yoshida, Daisuke; Shimamoto, Kazuaki

    2003-07-01

    Adiponectin, an adipocyte-derived protein, has been suggested to play an important role in insulin sensitivity. We examined the association between insulin sensitivity (M value) evaluated by the euglycemic-hyperinsulinemic glucose clamp and adiponectin concentrations in 30 essential hypertensives (EHT) and 20 normotensives (NT) and investigated the effect of blockade of the renin-angiotensin system (RAS) on adiponectin concentrations. EHT were divided into 12 insulin-resistant EHT (EHT-R) and 18 non-insulin-resistant EHT (EHT-N) using mean-1 SD of the M value in NT. There were no intergroup differences in age, gender, and body mass index (BMI). EHT-R had significantly higher levels of insulin and triglyceride and lower levels of adiponectin than did NT and EHT-N. EHT-R had higher levels of free fatty acid and lower levels of high-density lipoprotein (HDL) cholesterol than did EHT-N. Adiponectin concentrations were positively correlated with M value and HDL cholesterol and negatively correlated with BMI, insulin, free fatty acid, and triglyceride but not with blood pressure. M value, BMI, and HDL cholesterol were independent determinants of adiponectin concentrations in multiple and stepwise regression analyses. Sixteen EHT were treated with an angiotensin-converting enzyme inhibitor (temocapril, 4 mg/d; n=9) or an angiotensin II receptor blocker (candesartan, 8 mg/d; n=7) for 2 weeks. Treatment with temocapril or candesartan significantly decreased blood pressure and increased M value and adiponectin concentrations but did not affect BMI and HDL cholesterol. These results suggest that hypoadiponectinemia is related to insulin resistance in essential hypertension and that RAS blockade increases adiponectin concentrations with improvement in insulin sensitivity.

  18. Circulating Adiponectin Levels Following Treatment Can Predict Late Clinical Outcomes in Chronic Heart Failure

    PubMed Central

    Yu, Ho-Ping; Jen, Hsu-Lung; Yin, Wei-Hsian; Wei, Jeng

    2017-01-01

    Background Circulating adiponectin concentration increases in patients with chronic heart failure (HF). We sought to explore the prognostic value of temporal changes in adiponectin concentration following treatment for chronic HF. Methods Serum adiponectin levels were measured at baseline and after a 3-month anti-failure treatment in 124 patients with symptomatic chronic systolic HF. Major adverse cardiac events (MACE) including death, heart transplantation, or hospitalization with worsening HF during a median follow-up period of 752 days were determined. Results Univariate and multivariate analysis showed that high levels of adiponectin after a 3-month treatment were associated with a 3.8-fold increased risk of MACE (p = 0.03), independent of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Moreover, the combining of circulating levels of adiponectin with NT-proBNP provided independent and additional prognostic value in identifying high risk patients with MACE during follow-up. Conclusions Changes in adiponectin and NT-proBNP over time provide prognostic information. When adiponectin is used in conjunction with NT-proBNP in chronic HF, the prognostic value may be better than if each biomarker is used separately. PMID:28344417

  19. 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

  20. Total and high molecular weight adiponectin levels in the rat model of post-myocardial infarction heart failure.

    PubMed

    Kalisz, M; Baranowska, B; Wolinska-Witort, E; Maczewski, M; Mackiewicz, U; Tulacz, D; Gora, M; Martynska, L; Bik, W

    2015-10-01

    Adiponectin is a protein secreted primarily by adipose tissue. It has been suggested that adiponectin plays a protective role in the early phase following myocardial infarction. Our primary aim was to investigate the effects of post-myocardial infarction heart failure well-characterized by left ventricular hemodynamic parameters on the total and high molecular weight adiponectin concentrations in plasma, fat and cardiac tissue. Eight weeks after myocardial infarction or sham operation, total and high molecular weight adiponectin concentrations in plasma, fat, and cardiac tissues were assayed in rats. In addition, hemodynamic parameters and expression of the genes encoding atrial natriuretic peptide and brain natriuretic peptide in left ventricle were evaluated. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels in left ventricle tissue were higher in rats with myocardial infarction-induced heart failure compared with the controls. Similarly, total adiponectin concentration was increased in left ventricle (but not in right ventricle) in rats with post-myocardial infarction heart failure. In contrast, adiponectin levels in plasma and cardiac adipose tissue in rats with post-myocardial infarction heart failure were lower than in sham-operated animals. Furthermore, there were no significant differences in levels of high molecular weight adiponectin in plasma, cardiac tissue or adipose tissue between these two groups. We conclude that in the rat model of post-myocardial infarction heart failure, adiponectin level is increased in left ventricle tissue. This is accompanied by decreased adiponectin levels in plasma and cardiac adipose tissue.

  1. Pioglitazone increases secretion of high-molecular-weight adiponectin from adipocytes.

    PubMed

    Bodles, Angela M; Banga, Anannya; Rasouli, Neda; Ono, Fumiyo; Kern, Philip A; Owens, Randall J

    2006-11-01

    Adiponectin is an adipocyte-derived serum protein that plays important roles in energy homeostasis, obesity, and insulin sensitivity. Using sucrose gradients and Western blotting of nondenaturing gels, we examined the adiponectin isoforms secreted from human adipose tissue, human and mouse adipocytes, and cell lines in response to pioglitazone added in vitro. The predominant form secreted from adipose tissue in vitro was the high-molecular-weight (HMW) isoform, with small amounts of low-molecular-weight (LMW) forms present. The addition of pioglitazone (1-3 micromM) in vitro increased the secretion of the HMW isoform, with no significant effect on the other isoforms. Human adipose tissue was also examined for changes in adiponectin mRNA levels upon pioglitazone treatment. No difference was detected, suggesting that the effect of pioglitazone is not at the transcriptional level but, rather, at a posttranscriptional phase of the secretory pathway. Additional experiments were conducted to determine whether adiponectin expression was mechanistically similar in other adipose cells. Examination of primary human adipocytes revealed an increase in intracellular HMW isoform with a decline in LMW forms following pioglitazone treatment, with a corresponding increase in the secreted HMW form. Similar results were observed with primary mouse adipocytes, 3T3-F422A cells, and SGBS human adipocyte cells, although differences in the distribution of HMW and LMW isoforms were apparent between cell types. Although there are differences in isoforms between species, in all cases pioglitazone served to increase the secretion of the HMW form of adiponectin.

  2. Hypoglycemic effects of three Iranian edible plants; jujube, barberry and saffron: Correlation with serum adiponectin level.

    PubMed

    Hemmati, Mina; Asghari, Somaye; Zohoori, Elham; Karamian, Mehdi

    2015-11-01

    One of the most common disorders of the endocrine system is diabetes mellitus. This disease is associated with dyslipidemia. Adiponectin is a protein hormone that secreted by adipocytes and has an important role in regulating of glucose and fatty acid metabolic pathways. This study was designed to investigate the changes in serum level of adiponectin in diabetic rats treated with hydroalcoholic extracts of three medicinal plants; jujube (Ziziphus jujuba), barberry (Berberis vulgaris) and saffron (Crocus sativus) in comparison with quercetin. Streptozotocin -induced diabetic male rats were gavaged with specified doses of the extracts (25 and 100mg/kg) for two weeks. At the end of treatment period, fasting blood specimens were collected. The levels of adiponectin, fasting blood sugar (FBS), total Cholesterol, triglycerides, HDL-C and LDL-C were measured. Statistical analysis showed that serum levels of triglyceride and VLDL decreased significantly (P<0.05) in all treated groups. FBS level in all treated groups, decreased significantly and reach to normoglycemic level (P<0.05). Except Jujube, other plant extracts had no effect on cholesterol. Jujube in two doses (25 and 100mg/kg) could increased significantly HDL-C (P<0.05) with no effect on total cholesterol and LDL-C. Serum adiponectin level increased in all treated groups. These beneficial effects of C. sativus, B. vulgaris and Z. jujube extracts and quercetin in diabetic rats may be associated with increase in adiponectin level.

  3. Subetta treatment increases adiponectin secretion by mature human adipocytes in vitro.

    PubMed

    Nicoll, Jim; Gorbunov, Evgeniy A; Tarasov, Sergey A; Epstein, Oleg I

    2013-01-01

    Purpose. To investigate the mechanism of action in peripheral tissues of novel complex drug containing release-active dilutions of antibodies to the beta subunit of the insulin receptor and antibodies to endothelial nitric oxide synthase (Subetta), which has shown efficacy in animal models of diabetes. Methods. Human mature adipocytes were incubated either with Subetta, with one of negative controls (placebo or vehicle), with one of nonspecific controls (release-active dilutions of antibodies to cannabinoid receptor type I or release-active dilutions of rabbit nonimmune serum), or with dimethyl sulfoxide (DMSO) at 37°C in a humidified incubator at 5% CO2 for three days. Rosiglitazone was used as reference drug. Secretion of adiponectin was measured by quantitative enzyme-linked immunosorbent assay (ELISA). Results. Only Subetta significantly stimulates adiponectin production by mature human adipocytes. Nonspecific controls did not significantly affect adiponectin secretion, resulting in adiponectin levels comparable to background values of the negative controls and DMSO. Conclusion. Increasing adiponectin production in absence of insulin by Subetta probably via modulating effect on the beta subunit of the insulin receptor might serve as one of the mechanisms of the antidiabetic effect of this drug. These in vitro results give first insight on possible mechanism of action of Subetta and serve as a background for further studies.

  4. Circulating adiponectin levels in various malignancies: an updated meta-analysis of 107 studies

    PubMed Central

    Peng, Xin; Wu, Li-Ling; Yu, Guang-Yan

    2016-01-01

    Early detection of cancers is challenging for lack of specific biomarkers. Adiponectin is an adipokine predominantly derived from adipocytes and hypoadiponectinemia has been reported to associate with risk of many types of cancers. However, available evidence is controversial. Some studies show that increased adiponectin levels correlate with cancer risk. Therefore, we performed a meta-analysis of the association between circulating adiponectin levels and cancer development. A systematic search of PubMed, EMBASE, Wiley Online Library and Cochrane Library was conducted for eligible studies involving circulating adiponectin and malignancies from inception to August 8, 2015. Standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated by use of a random-effect model. Funnel plot and Egger's linear regression test were conducted to examine the risk of publication bias. 107 studies were included with 19,319 cases and 25,675 controls. The pooled analysis indicated that circulating adiponectin levels were lower in patients with various cancers than in controls, with a pooled SMD of −0.334 μg/ml (95% CI, −0.465 to −0.203, P = 0.000). No evidence of publication bias was observed. Circulating high molecular weight adiponectin levels were also lower in cancer patients than in controls, with a pooled SMD of −0.502 μg/ml (95% CI, −0.957 to −0.047, P = 0.000). This meta-analysis provides further evidence that decreased adiponectin levels is associated with risk of various cancers. Hypoadiponectinemia may represent a useful biomarker for early detection of cancers. PMID:27119501

  5. Circulating adiponectin levels in various malignancies: an updated meta-analysis of 107 studies.

    PubMed

    Wei, Tai; Ye, Peng; Peng, Xin; Wu, Li-Ling; Yu, Guang-Yan

    2016-07-26

    Early detection of cancers is challenging for lack of specific biomarkers. Adiponectin is an adipokine predominantly derived from adipocytes and hypoadiponectinemia has been reported to associate with risk of many types of cancers. However, available evidence is controversial. Some studies show that increased adiponectin levels correlate with cancer risk. Therefore, we performed a meta-analysis of the association between circulating adiponectin levels and cancer development. A systematic search of PubMed, EMBASE, Wiley Online Library and Cochrane Library was conducted for eligible studies involving circulating adiponectin and malignancies from inception to August 8, 2015. Standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated by use of a random-effect model. Funnel plot and Egger's linear regression test were conducted to examine the risk of publication bias. 107 studies were included with 19,319 cases and 25,675 controls. The pooled analysis indicated that circulating adiponectin levels were lower in patients with various cancers than in controls, with a pooled SMD of -0.334 μg/ml (95% CI, -0.465 to -0.203, P = 0.000). No evidence of publication bias was observed. Circulating high molecular weight adiponectin levels were also lower in cancer patients than in controls, with a pooled SMD of -0.502 μg/ml (95% CI, -0.957 to -0.047, P = 0.000). This meta-analysis provides further evidence that decreased adiponectin levels is associated with risk of various cancers. Hypoadiponectinemia may represent a useful biomarker for early detection of cancers.

  6. Adiponectin and colorectal cancer.

    PubMed

    Otani, Kensuke; Ishihara, Soichiro; Yamaguchi, Hironori; Murono, Koji; Yasuda, Koji; Nishikawa, Takeshi; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Kawai, Kazushige; Nozawa, Hiroaki; Watanabe, Toshiaki

    2017-02-01

    Colorectal cancer is an obesity-related malignancy. Adiponectin is an adipokine produced exclusively by adipose tissue, and its concentration in the serum is reduced in obesity. A low serum level of adiponectin is associated with an increased risk of various types of malignancies including colorectal cancer. These facts suggest that the epidemiological link between obesity and cancer may have a significant association with adiponectin. Although numerous studies of colorectal cancer have been reported, the results are conflicting about the anti-cancer effect of adiponectin, and how adiponectin affects carcinogenesis or cancer development remains controversial. Because adiponectin has multiple systemic effects and exists as a high serum concentration protein, the main role of adiponectin should be regulation of homeostasis, and it would not likely act as an anti-cancerous hormone. However, as epidemiological evidence shows, a low adiponectin level may be a basic risk factor for colorectal cancer. We speculate that when the colonic epithelium is stimulated or damaged by another carcinogen under the condition of a low adiponectin level, carcinogenesis is promoted and cancer development is facilitated. In this report, we summarize recent findings of the correlation between adiponectin and colorectal cancer and investigate the effect of adiponectin on colorectal cancer.

  7. Serum Adiponectin Level and Clinical, Metabolic, and Hormonal Markers in Patients with Polycystic Ovary Syndrome

    PubMed Central

    Yildiz, Yunus; Ozaksit, Gülnur; Serdar Unlu, Bekir; Ozgu, Emre; Energin, Hasan; Kaba, Metin; Ugur, Mustafa

    2014-01-01

    Background: To investigate the relationship between adiponectin, metabolic and hor- monal parameters, and insulin resistance in patients with non-treated polycystic ovary syndrome. Materials and Methods: In this cross-sectional observational study, 81 patients admitted to out-patient clinic with complaints of menstrual irregularity, hirsutism and obesity were enrolled. Serum adiponectin, biochemical and hormonal parameters, and 75 gram oral glu- cose tolerance test (OGTT) were measured. Spearman’s correlation coefficient was used for statistical analysis. Results: We observed inverse correlations between serum adiponectin level and body mass index, homeostasis model assessment insulin-resistance score, insulin level, fast- ing glucose level, and prolactin level (p=0.001, p=0.02, p=0.04, p=0.02, and p=0.005, respectively). No significant correlations were found between serum adiponectin level and age, height, weight, Ferriman-Gallwey score, 2 hours OGTT test value and free tes- tosterone level (p=0.3, p=0.6, p=0.2, p=0.8, p=0.9, and p=0.01, respectively). Conclusion: The present study demonstrated that in polycystic ovary syndrome patients, when serum adiponectin level decreased, degree of insulin resistance increased. Our find- ings indicate that serum adiponectin level is likely to be an adequate marker for deter- mination of the degree of insulin resistance, and may be a predictor of diseases, such as type 2 diabetes mellitus (T2DM) and metabolic syndrome, which develop on the basis of insulin resistance. PMID:24520503

  8. Fenofibrate administration to arthritic rats increases adiponectin and leptin and prevents oxidative muscle wasting

    PubMed Central

    Castillero, Estíbaliz; Martín, Ana Isabel; Nieto-Bona, Maria Paz; Fernández-Galaz, Carmen; López-Menduiña, María; Villanúa, María Ángeles; López-Calderón, Asunción

    2012-01-01

    Chronic inflammation induces skeletal muscle wasting and cachexia. In arthritic rats, fenofibrate, a peroxisome proliferator-activated receptor α (PPARα (PPARA)) agonist, reduces wasting of gastrocnemius, a predominantly glycolytic muscle, by decreasing atrogenes and myostatin. Considering that fenofibrate increases fatty acid oxidation, the aim of this study was to elucidate whether fenofibrate is able to prevent the effect of arthritis on serum adipokines and on soleus, a type I muscle in which oxidative metabolism is the dominant source of energy. Arthritis was induced by injection of Freund's adjuvant. Four days after the injection, control and arthritic rats were gavaged daily with fenofibrate (300 mg/kg bw) or vehicle over 12 days. Arthritis decreased serum leptin, adiponectin, and insulin (P<0.01) but not resistin levels. In arthritic rats, fenofibrate administration increased serum concentrations of leptin and adiponectin. Arthritis decreased soleus weight, cross-sectional area, fiber size, and its Ppar α mRNA expression. In arthritic rats, fenofibrate increased soleus weight, fiber size, and Ppar α expression and prevented the increase in Murf1 mRNA. Fenofibrate decreased myostatin, whereas it increased MyoD (Myod1) and myogenin expressions in the soleus of control and arthritic rats. These data suggest that in oxidative muscle, fenofibrate treatment is able to prevent arthritis-induced muscle wasting by decreasing Murf1 and myostatin expression and also by increasing the myogenic regulatory factors, MyoD and myogenin. Taking into account the beneficial action of adiponectin on muscle wasting and the correlation between adiponectin and soleus mass, part of the anticachectic action of fenofibrate may be mediated through stimulation of adiponectin secretion. PMID:23781298

  9. Effects of isotretinoin on body mass index, serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients

    PubMed Central

    Ayvaz, Havva Hilal; Ozturk, Gulfer; Ergin, Can; Akıs, Havva Kaya; Gonul, Muzeyyen; Arzuhal, Ercan

    2016-01-01

    Introduction Isotretinoin has been successfully used for the treatment of acne vulgaris. Aim To investigate the effects of isotretinoin on body mass index (BMI), to determine whether isotretinoin causes any changes in serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients, and to correlate variables. Material and methods Thirty-two patients were included in this study. Oral isotretinoin was begun at a dose of 0.5–0.6 mg/kg and raised to 0.6–0.75 mg/kg. Pretreatment and posttreatment third-month BMI and adiponectin, leptin, and ghrelin serum levels were measured. Results The pre- and posttreatment BMI values were not significantly different. In addition, serum adiponectin and leptin levels were significantly increased following isotretinoin therapy while serum ghrelin levels were not different. Conclusions Isotretinoin may exert its anti-inflammatory activity by increasing leptin and adiponectin levels. PMID:27605902

  10. Effects of L-thyroxine therapy on circulating leptin and adiponectin levels in subclinical hypothyroidism: a prospective study.

    PubMed

    Yildiz, Bulent Okan; Aksoy, Duygu Yazgan; Harmanci, Ayla; Unluturk, Ugur; Cinar, Nese; Isildak, Mehlika; Usman, Aydan; Bayraktar, Miyase

    2013-05-01

    Subclinical hypothyroidism (SCH) is defined by increased thyrotropin (TSH) and normal free thyroxine (fT4) levels. Controversial data are available regarding the effects of SCH on adipose tissue. Adiponectin and leptin are two major adipokines secreted from adipose tissue. We aimed to determine the levels of adiponectin and leptin in women with SCH and potential effects of L-thyroxine therapy on those levels. Forty three women with SCH and 53 age- and BMI-matched healthy euthyroid control women were included. Adiponectin and leptin levels, total cholesterol (TC), triglycerides (TG), HDL-, and LDL cholesterol, fat mass (FM) and fat-free mass (FFM) were determined in all participants. Patients received L-thyroxine treatment for 6 months after which all measurements were repeated. Patients with SCH and controls had similar baseline values for adiponectin, leptin, lipids, FM and FFM. All patients reached euthyroid status after 6 months of replacement therapy. Treatment resulted in an increase in adiponectin (p <0.01) and a decrease in leptin levels (p <0.05). Lipid levels, FM and FFM did not show a significant change. Achievement of euthyroid status by replacement therapy increases adiponectin and decreases leptin levels in women with SCH in this prospective study independent of a change in body fat mass.

  11. 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.

  12. Feeding a Modified Fish Diet to Bottlenose Dolphins Leads to an Increase in Serum Adiponectin and Sphingolipids

    PubMed Central

    Sobolesky, Philip M.; Harrell, Tyler S.; Parry, Celeste; Venn-Watson, Stephanie; Janech, Michael G.

    2016-01-01

    Feeding a modified fish diet has been suggested to improve insulin sensitivity in bottlenose dolphins; however, insulin sensitivity was not directly measured. Since demonstrating an improvement in insulin sensitivity is technically difficult in dolphins, we postulated that directional changes in the hormone axis: fibroblast growth factor 21 (FGF21)/Adiponectin/Ceramide (Cer), could provide further support to this hypothesis. We measured 2-h post-prandial serum FGF21, total adiponectin, percent unmodified adiponectin, ceramide, and sphingosine levels from dolphins fed a diet rich in heptadecanoic acid (C17:0) over 24 weeks. Serum FGF21 was quantified by ELISA with an observed range of 129–1599 pg/ml, but did not significantly change over the 24-week study period. Total adiponectin levels (mean ± SD) significantly increased from 776 ± 400 pmol/ml at week 0 to 1196 ± 467 pmol/ml at week 24. The percent unmodified adiponectin levels (mean ± SD) decreased from 23.8 ± 6.0% at week 0 to 15.2 ± 5.2% at week 24. Interestingly, although FGF21 levels did not change, there was a good correlation between FGF21 and total adiponectin (ρ = 0.788, P < 0.001). We quantified the abundances of serum ceramides and sphingosines (SPH) because adiponectin has a defined role in sphingolipid metabolism through adiponectin receptor-mediated activation of ceramidases. The most abundant ceramide in dolphin sera was Cer 24:1 comprising 49% of the ceramides measured. Significant reductions were observed in the unsaturated Cer 18:1, Cer 20:1, and Cer 24:1, whereas significant increases were observed in saturated Cer 22:0, Cer 24:0, and Cer 26:0. However, total serum ceramides did not change. Significant elevations were detected for total sphingosine, dihydrosphingosine, sphingosine-1-phosphate, and dihydrosphingosine-1-phosphate. Proteomic analysis of the serum proteins revealed few changes in serum proteins over the study period. In conclusion

  13. Obesity indices and metabolic markers are related to hs-CRP and adiponectin levels in overweight and obese females.

    PubMed

    Sanip, Zulkefli; Ariffin, Farah Diana; Al-Tahami, Belqes Abdullah Mohammed; Sulaiman, Wan Azman Wan; Rasool, Aida Hanum Ghulam

    2013-01-01

    Obese subjects had increased serum high sensitivity C-reactive protein (hs-CRP), decreased adiponectin levels, and impaired microvascular endothelial function compared to lean subjects. We investigated the relationships of serum hs-CRP, adiponectin and microvascular endothelial function with obesity indices and metabolic markers in overweight and obese female subjects. Anthropometric profile, body fat composition, biochemical analysis, serum hs-CRP and adiponectin levels, and microvascular endothelial function were measured in 91 female subjects. Microvascular endothelial function was determined using laser Doppler fluximetry and the process of iontophoresis. Mean age and body mass index (BMI) of subjects were 34.88 (7.87) years and 32.93 (4.82) kg/m(2). hs-CRP levels were positively correlated with weight, BMI, waist circumference, hip circumference, body fat and visceral fat. Adiponectin levels were positively correlated with insulin sensitivity index (HOMA-%S), and inversely correlated with waist hip ratio, triglyceride, fasting insulin and insulin resistance index (HOMA-IR). No relationship was seen between microvascular endothelial function and obesity indices, and metabolic markers. In overweight and obese female subjects, hs-CRP levels were correlated with obesity indices while adiponectin levels were inversely correlated with obesity indices and metabolic markers. No significant relationship was seen between microvascular endothelial function with obesity indices and metabolic markers including hs-CRP and adiponectin in female overweight and obese subjects.

  14. Docosahexaenoic acid increases cellular adiponectin mRNA and secreted adiponectin protein, as well as PPARγ mRNA, in 3T3-L1 adipocytes.

    PubMed

    Oster, Richard T; Tishinsky, Justine M; Yuan, Zongfei; Robinson, Lindsay E

    2010-12-01

    Adiponectin, a protein secreted from adipose tissue, has been shown to have anti-diabetic and anti-inflammatory effects, but its regulation is not completely understood. Long-chain n-3 fatty acids eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3; DHA) may be involved in adiponectin regulation as they are potential ligands for peroxisome proliferator-activated receptor-γ (PPARγ), a key transcription factor for the adiponectin gene. To examine this, 3T3-L1 adipocytes were incubated with 125 µmol·L-1 EPA, DHA, palmitic, or oleic acids complexed to albumin, or with albumin alone (control) for 24 h. Adipocytes were also incubated for 24 h with EPA and DHA plus bisphenol-A-diglycidyl ether (BADGE), a PPARγ antagonist. Both EPA and DHA increased (p < 0.05) secreted adiponectin concentration compared with the control (44% and 102%, respectively), but did not affect cellular adiponectin protein content. Incubation with BADGE and DHA inhibited increases in secreted adiponectin protein, suggesting that DHA may act through a PPARγ-dependent mechanism. However, BADGE had no effect on EPA-induced increases in secreted adiponectin protein. Only DHA enhanced (p < 0.05) PPARγ and adiponectin mRNA expression compared wtih the control. Our results demonstrate that DHA increases cellular adiponectin mRNA and secreted adiponectin protein in 3T3-L1 adipocytes, possibly by a mechanism involving PPARγ. Moreover, DHA increased adiponectin concentration to a greater extent (40% more, p < 0.05) compared with EPA, emphasizing the need to consider the independent actions of EPA and DHA in adipocytes.

  15. Normal total and high molecular weight adiponectin levels in adults with cystic fibrosis.

    PubMed

    Ziai, S; Elisha, B; Hammana, I; Tardif, A; Berthiaume, Y; Coderre, L; Rabasa-Lhoret, R

    2011-12-01

    Cystic fibrosis related diabetes (CFRD) is an important complication of CF that increases mortality. Adiponectin, an adipokine secreted from adipose tissue, plays an important role in fatty acid and glucose metabolism. Lower total adiponectin (TA) levels have been linked to the risk of developing type 2 diabetes. However, studies show that the high molecular weight isoform (HMW), thought to be more active than TA, might be a better indicator of insulin sensitivity. Our aim was to determine the association between HMW and insulin sensitivity in CF subjects and determine if other factors might modulate its levels. Thirteen control subjects and 47 CF adults (16 with normal glucose tolerance, 16 prediabetic and 15 with CFRD) underwent an oral glucose tolerance test. Blood samples were taken at time 0, 30, 60, 90 and 120 min. Body mass index, fibrinogen, glucose and insulin, TA and HMW were measured in every subject. Regression analysis was used to determine the association between TA, HMW and glucose (fasting glucose, 2h glucose and glucose AUC) as well as insulin (fasting insulin, insulin AUC, and Stumvoll insulin sensitivity index) parameters. TA and HMW levels were similar between CF patients and controls and were not associated to insulin sensitivity. TA was negatively associated to insulin AUC (p=0.0108) and 2h glucose (p=0.0116) in controls while these relationships were either weakly negative (p=0.0208) or weakly positive (p=0.0105) in CF patients. Also, HMW was negatively associated to insulin (p=0.00301) and glucose AUC (p=0.0546) in controls whereas these associations were positive in CF patients (p=0.0388, p=0.0232 respectively). In conclusion, our exploratory study on HMW adiponectin demonstrated similar levels of TA and HMW between CF patients and controls and different relationships between forms of adiponectin to glucose metabolism and insulin in CF.

  16. Cardioprotective effect of intermittent fasting is associated with an elevation of adiponectin levels in rats.

    PubMed

    Wan, Ruiqian; Ahmet, Ismayil; Brown, Martin; Cheng, Aiwu; Kamimura, Naomi; Talan, Mark; Mattson, Mark P

    2010-05-01

    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 (MI) 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 h 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 MI. 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.

  17. The rapid increase of circulating adiponectin in neonatal calves depends on colostrum intake.

    PubMed

    Kesser, J; Hill, M; Heinz, J F L; Koch, C; Rehage, J; Steinhoff-Wagner, J; Hammon, H M; Mielenz, B; Sauerwein, H; Sadri, H

    2015-10-01

    blood concentrations of adiponectin and placental transfer of adiponectin to the bovine fetus is unlikely. In conclusion, colostrum intake is essential for the postnatal increase of circulating adiponectin in newborn calves.

  18. Increased plasma isoprostane is associated with visceral fat, high molecular weight adiponectin, and metabolic complications in obese children.

    PubMed

    Araki, Shunsuke; Dobashi, Kazushige; Yamamoto, Yukiyo; Asayama, Kohtaro; Kusuhara, Koichi

    2010-08-01

    Oxidative stress is considered to be increased in obese subjects. However, the association of oxidative stress with visceral adiposity and adiponectin level is not fully understood in children. Forty-four obese Japanese children and adolescents, 28 boys and 16 girls, with median age of 9.9 years [5.2-13.8 years], and the 28 age-matched non-obese healthy controls, 15 boys and 13 girls, were enrolled in this study. The median BMI Z scores were +2.21 [1.31-4.38] for the obese subjects and -0.72 [-2.11-1.31] for the control. Plasma concentrations of 8-epi-prostaglandin F₂α (isoprostane), a marker of oxidative stress, and adiponectin fractions were assayed using ELISA. 8-epi-PGF₂α levels were significantly higher in the obese group (37.1 [4.7-112.7], median and the range) than in the control (11.5 [4.5-27.3]). In a univariate analysis, concentrations of 8-epi-PGF₂α positively correlated with visceral adipose tissue area measured by computed tomography, waist circumference, serum triglycerides, alanine aminotransferase, insulin levels, and the homeostasis of minimal assessment of insulin resistance and inversely correlated with high-density-lipoprotein cholesterol and high-molecular weight (HMW) adiponectin. Total-, medium-, or low-molecular weight adiponectin fraction did not show a significant correlation with 8-epi-PGF₂α Forty of 44 obese children had one or more metabolic complications. The 8-epi-PGF[Formula: see text] levels also elevated with increasing numbers of obesity-related complications. These results suggest that oxidative stress is enhanced in relation to visceral fat accumulation and decreasing HMW adiponectin level in childhood obesity. Oxidative stress may be associated with the development of obesity-related complications.

  19. Effects of aging on the plasma levels of nesfatin-1 and adiponectin

    PubMed Central

    LI, JIANG-BO; NISHIDA, MIYUKI; KAIMOTO, KAORI; ASAKAWA, AKIHIRO; CHAOLU, HUHE; CHENG, KAI-CHUN; LI, YING-XIAO; TERASHI, MUTSUMI; KOYAMA, KEN ICHIRO; AMITANI, HARUKA; SAKOGUCHI, TAKEO; USHIKAI, MIHARU; IKEDA, SATOSHI; AOYAMA, KOHJI; HORIUCHI, MASAHISA; LI, JIAN-ZHONG; INUI, AKIO

    2014-01-01

    Gastric and adipose tissue secrete a number of hormones that are involved in energy metabolism. The biological functions of these hormones, including their effects on aging, are currently under investigation. Adiponectin was shown to be directly involved in appetite and the control of body weight. However, the effects of aging of nesfatin-1, an appetite-suppressing peptide that was recently identified, have not yet been fully elucidated. The aim of this study was to determine the effects of aging on the plasma levels of nesfatin-1 and adiponectin. Our results demonstrated no significant differences in the nesfatin-1 plasma levels among three age groups (2, 6 and 24 months) of female BALB/c mice. The plasma nesfatin-1 levels/visceral fat (VF) ratio in the 24-month-old mice was significantly lower compared to that in the 2- and 6-month-old mice. In addition, there were no significant differences in the plasma adiponectin levels among the three age groups. The plasma adiponectin levels/VF ratio in the 24-month-old mice was significantly lower compared to that in the 2- and 6-month-old mice. In conclusion, there were no age-related changes in the plasma levels of nesfatin-1 and adiponectin, although the ratio of plasma levels of nesfatin-1 and adiponectin per VF was decreased with advancing age. Our results indicated that nesfatin-1 and adiponectin may be involved in controlling energy balance during aging. PMID:24649088

  20. The Role of Alcohol Consumption in Regulating Circulating Levels of Adiponectin: A Prospective Cohort Study

    PubMed Central

    Britton, Annie

    2015-01-01

    Context: The role of alcohol intake in influencing longitudinal trajectories of adiponectin is unclear. Objective: The objective of the study was to examine the association between alcohol intake and changes in the circulating levels of adiponectin over repeat measures. Design, Setting, and Participants: A prospective cohort study of 2855 men and women (74% men with a mean age of 50 y at baseline) drawn from the Whitehall II study. Data from study phases 3 (1991–1993), 5 (1997–1999), and 7 (2002–2004) were used. Main Outcome Measure: Adiponectin serum concentrations (nanograms per milliliter) were measured, and alcohol intake was defined in terms of number of UK units (1 U = 8 g ethanol) consumed in the previous 7 days on three occasions. Cross-sectional associations between alcohol and adiponectin levels were calculated using linear regression. A bivariate dual-change score model was used to estimate the effect of alcohol intake on upcoming change in adiponectin. Models were adjusted for age, sex, ethnicity, and smoking status. Results: Alcohol consumption was cross-sectionally associated with (log transformed) adiponectin levels (β ranging from .001 to .004, depending on phase and level of adjustment) but was not associated with changes in adiponectin levels over time [γ = −0.002 (SE 0.002), P = 0.246]. Conclusion: Alcohol intake is not associated with changes in circulating adiponectin levels in this cohort. This finding provides evidence that adiponectin levels are unlikely to mediate the relationship between moderate alcohol consumption and reduced risk of type 2 diabetes. It is important to consider dynamic longitudinal relationships rather than cross-sectional associations. PMID:26000546

  1. 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

    SciTech Connect

    Yamane, Takumi; Kobayashi-Hattori, Kazuo; Oishi, Yuichi

    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 along 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.

  2. Adiponectin serum levels correlate with insulin resistance in type 2 diabetic patients

    PubMed Central

    Aleidi, Shereen; Issa, Ala; Bustanji, Haidar; Khalil, Mohammad; Bustanji, Yasser

    2014-01-01

    The adipose tissue is not only an inert storage depot for lipids, but also it secretes a variety of bioactive molecules, known as adipokines, which affect whole-body homeostasis. Adiponectin is the most abundant of these adipocytokines and is known to have a regulatory effect on the metabolism of glucose and lipid. The main objectives of this study were to evaluate the serum levels of adiponectin and to establish a correlation between adiponectin serum levels and the degree of insulin resistance in type 2 diabetic patients. Eighty participants were enrolled in this study; 61 type 2 diabetic patients and 19 apparently healthy subjects. Serum level of adiponectin was measured by enzyme-linked immunosorbent assay (ELISA) for each participant. Data collection sheet was filled with all required information for each participant. Adiponectin level in the diabetic patients (5.05 ± 2.61 μg/ml) was lower than in non-diabetic healthy controls (5.71 ± 2.35 μg/ml). When the results were compared according to gender, diabetic females showed significantly higher adiponectin levels (5.76 ± 2.64 μg/ml) than diabetic males (4.366 ± 2.43 μg/ml, P = 0.035). In addition, female diabetic patients with abdominal obesity (waist circumference (WC) ⩾ 88 cm) had lower adiponectin levels (5.58 ± 2.58 μg/ml) than diabetic females without abdominal obesity (6.96 ± 3.12 μg/ml). The correlation analysis indicated that adiponectin had a significant positive correlation with age (r = −0.450, P < 0.001). In conclusion, female diabetic patients had a statistically significant higher adiponectin level than male diabetic patients which could indicate a gender effect. Adiponectin levels were inversely related to insulin resistance; as patients with abdominal obesity had lower serum levels of adiponectin. PMID:26106273

  3. Adiponectin is Associated with Increased Mortality and Heart Failure in Patients with Stable Ischemic Heart Disease: Data from the Heart and Soul Study

    PubMed Central

    Beatty, Alexis L.; Zhang, Mary H.; Ku, Ivy A.; Na, Beeya; Schiller, Nelson B.; Whooley, Mary A.

    2011-01-01

    Objective Serum adiponectin protects against incident ischemic heart disease (IHD). However, in patients with existing IHD, higher adiponectin levels are paradoxically associated with worse outcomes. We investigated this paradox by evaluating the relationship between adiponectin and cardiovascular events in patients with existing IHD. Methods We measured total serum adiponectin and cardiac disease severity by stress echocardiography in 981 outpatients with stable IHD who were recruited for the Heart and Soul Study between September 2000 and December 2002. Subsequent heart failure hospitalizations, myocardial infarction, and death were recorded. Results During an average of 7.1 years of follow-up, patients with adiponectin levels in the highest quartile were more likely than those in the lowest quartile to be hospitalized for heart failure (23% vs. 13%; demographics-adjusted hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.04–2.56, p=0.03) or die (49% vs. 31%; HR 1.67, 95% CI 1.24–2.26, p<0.008), but not more likely to have a myocardial infarction (12% vs. 17%; HR 0.64, 95% CI 0.38–1.06, p=0.08). The combined outcome of myocardial infarction, heart failure, or death occurred in 56% (136/245) of participants in the highest quartile of adiponectin vs. 38% (94/246) of participants in the lowest quartile (HR 1.54, 95% CI 1.31–2.21, p<0.002). Adjustment for left ventricular ejection fraction, diastolic dysfunction, inducible ischemia, C-reactive protein, and NT-proBNP attenuated the association between higher adiponectin and increased risk of subsequent events (HR 1.43, 95% CI 0.98–2.09 p=0.06). Conclusions Higher concentrations of adiponectin were associated with heart failure and mortality among patients with existing IHD. PMID:22196150

  4. Association between Risk Factors for Vascular Dementia and Adiponectin

    PubMed Central

    Lee, Won Taek; Park, Kyung Ah

    2014-01-01

    Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine secreted by adipose tissue. Adiponectin is widely known as a regulating factor related to cardiovascular disease and diabetes. Adiponectin plasma levels decrease with age. Decreased adiponectin increases the risk of cardiovascular disease and diabetes. Adiponectin improves hypertension and atherosclerosis by acting as a vasodilator and antiatherogenic factor. Moreover, adiponectin is involved in cognitive dysfunction via modulation of insulin signal transduction in the brain. Case-control studies demonstrate the association between low adiponectin and increased risk of stroke, hypertension, and diabetes. This review summarizes the recent findings on the association between risk factors for vascular dementia and adiponectin. To emphasize this relationship, we will discuss the importance of research regarding the role of adiponectin in vascular dementia. PMID:24860814

  5. 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

  6. 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

  7. Activation of AMPK by berberine promotes adiponectin multimerization in 3T3-L1 adipocytes.

    PubMed

    Li, Yun; Wang, Pengcheng; Zhuang, Yuan; Lin, Huan; Li, Yehua; Liu, Ling; Meng, Qinghang; Cui, Ting; Liu, Jing; Li, Zhen

    2011-06-23

    Adiponectin is assembled into trimer (LMW), hexamer (MMW) and high-molecular-weight (HMW) multimer in adipocytes. The HMW adiponectin is more metabolically active and closely associated with peripheral insulin sensitivity. In this study, we reported that berberine, an isoquinoline alkaloid with insulin-sensitizing effect, inhibits the expression of adiponectin, but promotes the assembly of HMW adiponectin and increases the ratio of HMW to total adiponectin. Berberine activates AMPK. Knockdown of AMPKα1 abolishes the effect of berberine. Activation of AMPK by AICAR also increases the level of HMW adiponectin. Our study suggested that activation of AMPK by berberine promotes adiponectin multimerization.

  8. Leptin and adiponectin levels in girls with central precocious puberty before and during GnRH agonist treatment

    PubMed Central

    Yoo, Jae Won; Song, Chun Woo

    2016-01-01

    Purpose The effects of gonadotropin-releasing hormone agonist (GnRHa) treatment on the energy metabolism in girls with central precocious puberty (CPP) are controversial. We focused the changes and related factors of serum levels of leptin and adiponectin in girls with CPP before and during GnRHa treatment. Methods Thirty girls with idiopathic CPP were enrolled in the study. Their auxological data and fasting blood were collected at the baseline and after six months of GnRHa treatment. Results After treatment, height (P<0.001), weight (P<0.001), and serum leptin levels (P=0.033) were significantly increased, whereas body mass index (BMI), homeostasis model of assessment-insulin resistance, serum adiponectin levels, and adiponectin/leptin ratio exhibited no significant changes. A Pearson correlation analysis showed that height, weight, BMI, and their standard deviation scores (SDSs), but not basal LH, FSH, and estradiol, were significantly correlated with serum leptin levels before and after GnRHa treatment. After a multiple linear regression analysis, only BMI was associated with serum leptin levels. Moreover, leptin SDSs adjusted for BMI were not significantly different before and after GnRHa. The Δ leptin levels (r2=0.207, P=0.012), but not with Δ leptin SDS (r2=0.019, P=0.556), during GnRHa treatment were positively correlated with Δ BMI. Conclusion These results suggest that GnRHa treatment in girls with CPP does not affect serum levels of leptin and adiponectin and insulin resistance. Serum leptin levels were depend on the changes in BMI during GnRHa treatment. PMID:28164072

  9. Evaluation of body weight, insulin resistance, leptin and adiponectin levels in premenopausal women with hyperprolactinemia.

    PubMed

    Atmaca, Aysegul; Bilgici, Birsen; Ecemis, Gulcin Cengiz; Tuncel, Ozgur Korhan

    2013-12-01

    The effects of hyperprolactinemia on metabolic parameters are not clear and a few data evaluating adiponectin levels in prolactinoma and idiopathic hyperprolactinemia exist. The aim of this study was to evaluate the effects of hyperprolactinemia on body weight, insulin resistance, beta cell function, and leptin and adiponectin levels in premenopausal women with hyperprolactinemia. Forty premenopausal women with prolactinoma or idiopathic hyperprolactinemia were compared to 41 age-matched healthy premenopausal women with regard to body weight, body mass index, waist and hip circumferences, waist to hip ratio, fasting plasma glucose, insulin levels, insulin resistance measured by homeostasis model assessment (HOMA)-insulin resistance index, beta cell function measured by HOMA-β index, leptin and adiponectin levels. Plasma insulin levels and HOMA indexes (both insulin resistance and beta indexes) were significantly higher in hyperprolactinemic women. The other parameters were similar between both groups. There was a positive correlation between prolactin levels and fasting plasma glucose in hyperprolactinemic women. The results of this study showed that high prolactin levels may be associated with hyperinsulinemia and insulin resistance in premenopausal women. This effect seems to be independent of body weight, leptin and adiponectin levels. High prolactin levels may directly stimulate insulin secretion from pancreas and directly cause hepatic and whole-body insulin resistance.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  11. Serum Adiponectin Levels, Neuroimaging, and Cognition in the Mayo Clinic Study of Aging

    PubMed Central

    Wennberg, Alexandra M. V.; Gustafson, Deborah; Hagen, Clinton E.; Roberts, Rosebud O.; Knopman, David; Jack, Clifford; Petersen, Ronald C.; Mielke, Michelle M.

    2016-01-01

    BACKGROUND Adiponectin, a protein involved in inflammatory pathways, may impact the development and progression of Alzheimer’s disease (AD). Adiponectin levels have been associated with mild cognitive impairment (MCI) and AD; however, its association with Alzheimer-associated neuroimaging and cognitive outcomes is unknown. OBJECTIVE Determine the cross-sectional association between plasma adiponectin and neuroimaging and cognitive outcomes in an older population-based sample. METHODS Multivariable adjusted regression models were used to investigate the association between plasma adiponectin and hippocampal volume (HVa), PiB-PET, FDG PET, cortical thickness, MCI diagnosis, and neuropsychological test performance. Analyses included 535 non-demented participants aged 70 and older enrolled in the Mayo Clinic Study of Aging. RESULTS Women had higher adiponectin than men (12,631 ng/mL vs. 8,908 ng/mL, P < .001). Among women, higher adiponectin was associated with smaller HVa (B=−0.595; 95% CI −1.19, −0.005), poorer performance in language (B−0.676; 95% CI −1.23, −0.121) and global cognition (B=−0.459; 95% CI −0.915, −0.002), and greater odds of a MCI diagnosis (OR=6.23; 95% CI 1.20, 32.43). In analyses stratified by sex and elevated amyloid (PiB-PET SUVR>1.4), among women with elevated amyloid, higher adiponectin was associated with smaller HVa (B=−0.723; 95% CI −1.43, −0.014), poorer performance in memory (B=−1.02; 95% CI −1.73, −0.312), language (B=−0.896; 95% CI −1.58, −0.212), and global (B=−0.650; 95% CI −1.18, −0.116) cognition, and greater odds of MCI (OR=19.34; 95% CI 2.72, 137.34). CONCLUSION Higher plasma adiponectin was associated with neuroimaging and cognitive outcomes among women. Longitudinal analyses are necessary to determine whether higher adiponectin predicts neurodegeneration and cognitive decline. PMID:27163809

  12. Increased beta -oxidation but no insulin resistance or glucose intolerance in mice lacking adiponectin.

    PubMed

    Ma, Ke; Cabrero, Agatha; Saha, Pradip K; Kojima, Hideto; Li, Lan; Chang, Benny Hung-Junn; Paul, Antoni; Chan, Lawrence

    2002-09-20

    Previous reports showed that recombinant fragments of adiponectin (adipo) displayed pharmacological effects when injected into rodents, but the relevance of these observations to the physiological function of adipo is unclear. We generated Adipo(-/-) mice by gene targeting. Adipo(-/-) mice are fertile with normal body and fat pad weights. Plasma glucose and insulin levels of Adipo(-/-) and Adipo(+/+) mice are similar under fasting conditions and during an intraperitoneal glucose tolerance test (GTT). Insulin tolerance test (ITT) also produces similar plasma glucose and insulin levels in the two groups of mice. Hyperinsulinemic-euglycemic clamp analysis showed that Adipo(-/-) and Adipo(+/+) mice have similar glucose infusion rates to maintain a similar serum glucose. High-fat diet feeding for 7 months led to similar weight gain and similar GTT and ITT responses. We next measured beta-oxidation and found it to be significantly increased in muscle and liver of Adipo(-/-) mice. In conclusion, our study indicates that absence of adipo causes increased beta-oxidation but does not cause glucose intolerance or insulin resistance in mice.

  13. Association of adiponectin gene polymorphism 45TG with gestational diabetes mellitus diagnosed on the new IADPSG criteria, plasma adiponectin levels and adverse pregnancy outcomes.

    PubMed

    Han, Yun; Zheng, Yan-li; Fan, Yu-ping; Liu, Man-hua; Lu, Xiao-yan; Tao, Qian

    2015-02-01

    The aim of this study was to identify the association of adiponectin gene single nucleotide polymorphism (SNP) 45TG with gestational diabetes mellitus (GDM) diagnosed on the new International Diabetes in Pregnancy Consensus Group (IADPSG) criteria, plasma adiponectin levels and adverse pregnancy outcomes in Han women of Nantong area in China. This cross-sectional study included 128 pregnant women with GDM (GDM group) and 140 pregnant women with normal glucose tolerance (NGT group) according to oral glucose tolerance test results based on the new IADPSG criteria. The GDM pregnant women were treated by diet control or diet control and insulin injection. All pregnant women attended antenatal cares and were recorded until delivery. Adiponectin gene was amplified through PCR, and SNP was detected using restriction enzyme SmaI. Plasma adiponectin levels were measured by ELISA. The G allele and TG+GG genotype were significantly more frequent than the T allele in the GDM group than in the NGT group (p < 0.05). Plasma adiponectin concentrations of TG+GG genotype carriers were significantly lower than those of TT genotype in both groups (p < 0.01). After adjustment for confounding factors, plasma adiponectin level remained significantly lower in pregnant women with TG+GG genotype than those with TT genotype (p < 0.05). Compared with the NGT group, the GDM group with glycemic control still had significantly higher incidences of macrosomia, neonatal hypoglycemia and asphyxia (p < 0.05). Further analysis revealed that the incidences of macrosomia and neonatal hypoglycemia were significantly higher in pregnant women with TG+GG genotype than those with TT genotype after adjustment for potential confounders in affecting pregnancy outcomes (p < 0.05). Even though pregnant women are diagnosed as GDM according to the new IADPSG criteria, the adiponectin SNP45 may be closely correlated with the prevalence of GDM in Han women of Nantong area in China, and the allele +45G in adiponectin

  14. Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats.

    PubMed

    Rossi, Andrea S; Lombardo, Yolanda B; Lacorte, Jean-Marc; Chicco, Adriana G; Rouault, Christine; Slama, Gérard; Rizkalla, Salwa W

    2005-08-01

    Insulin resistance and adiposity induced by a long-term sucrose-rich diet (SRD) in rats could be reversed by fish oil (FO). Regulation of plasma leptin and adiponectin levels, as well as their gene expression, by FO might be implicated in these findings. This study was designed to evaluate the long-term regulation of leptin and adiponectin by dietary FO in a dietary model of insulin resistance induced by long-term SRD in rats and to determine their impact on adiposity and insulin sensitivity. Rats were randomized to consume a control diet (CD; n = 25) or an SRD (n = 50) for 7 mo. Subsequently, the SRD-fed rats were randomized to consume SRD+FO or to continue on SRD for an additional 2 mo. Long-term SRD induced overweight and decreased both plasma leptin and adiponectin levels without change in gene expression. Dyslipidemia, adiposity, and insulin resistance accompanied these modifications. Shifting the source of fat to FO for 2 mo increased plasma levels of both adipokines, reversed insulin resistance and dyslipidemia, and improved adiposity. These results were not associated with modifications in gene expression. These results suggest that increasing both adipokines by dietary FO might play an essential role in the normalization of insulin resistance and adiposity in dietary-induced, insulin-resistant models.

  15. Association between adipose tissue expression and serum levels of leptin and adiponectin in women with polycystic ovary syndrome.

    PubMed

    Lecke, S B; Morsch, D M; Spritzer, P M

    2013-02-28

    We reviewed emerging evidence linking serum levels and adipose tissue expression of leptin and adiponectin in women with polycystic ovary syndrome (PCOS). Previous data obtained by our group from a sample of overweight/obese PCOS women and a control sample of normal weight controls, both stratified by BMI, were reanalyzed. Circulating levels of leptin and adiponectin were determined by commercially available enzyme-linked immunosorbent assays. Adipose tissue total RNA was reserve-transcripted into complementary DNA samples, which were used as templates for quantitative real-time PCR amplification. Positive correlations were found between serum and mRNA levels for both leptin (r = 0.321; P = 0.005) and adiponectin (r = 0.266; P = 0.024). Determination of leptin and adiponectin serum levels could serve as an indirect method to assess adipocyte production, since leptin and adiponectin are predominantly produced by subcutaneous adipocytes in women.

  16. Implication of low HDL-c levels in patients with average LDL-c levels: a focus on oxidized LDL, large HDL subpopulation, and adiponectin.

    PubMed

    Mascarenhas-Melo, Filipa; Sereno, José; Teixeira-Lemos, Edite; Marado, Daniela; Palavra, Filipe; Pinto, Rui; Rocha-Pereira, Petronila; Teixeira, Frederico; Reis, Flávio

    2013-01-01

    To evaluate the impact of low levels of high density lipoprotein cholesterol (HDL-c) on patients with LDL-c average levels, focusing on oxidative, lipidic, and inflammatory profiles. Patients with cardiovascular risk factors (n = 169) and control subjects (n = 73) were divided into 2 subgroups, one of normal HDL-c and the other of low HDL-c levels. The following data was analyzed: BP, BMI, waist circumference and serum glucose Total-c, TGs, LDL-c, oxidized LDL, total HDL-c and subpopulations (small, intermediate, and large), paraoxonase-1 (PON1) activity, hsCRP, uric acid, TNF- α , adiponectin, VEGF, and iCAM1. In the control subgroup with low HDL-c levels, significantly higher values of BP and TGs and lower values of PON1 activity and adiponectin were found, versus control normal HDL-c subgroup. However, differences in patients' subgroups were clearly more pronounced. Indeed, low HDL-c subgroup presented increased HbA1c, TGs, non-HDL-c, Ox-LDL, hsCRP, VEGF, and small HDL-c and reduced adiponectin and large HDL. In addition, Ox-LDL, large-HDL-c, and adiponectin presented interesting correlations with classical and nonclassical markers, mainly in the normal HDL-c patients' subgroup. In conclusion, despite LDL-c average levels, low HDL-c concentrations seem to be associated with a poor cardiometabolic profile in a population with cardiovascular risk factors, which is better evidenced by traditional and nontraditional CV biomarkers, including Ox-LDL, large HDL-c, and adiponectin.

  17. Phycocyanin prevents hypertension and low serum adiponectin level in a rat model of metabolic syndrome.

    PubMed

    Ichimura, Mayuko; Kato, Shigeko; Tsuneyama, Koichi; Matsutake, Sachiko; Kamogawa, Mai; Hirao, Eri; Miyata, Ayako; Mori, Sawako; Yamaguchi, Noriaki; Suruga, Kazuhito; Omagari, Katsuhisa

    2013-05-01

    Endothelial dysfunction is associated with hypertension, atherosclerosis, and metabolic syndrome. Phycocyanin is a pigment found in the blue-green algae, Spirulina, which possesses antihypertensive effect. In this study, we hypothesized that phycocyanin derived from Spirulina exerts antihypertensive actions by improving endothelial dysfunction in metabolic syndrome. Spontaneously hypertensive/NIH-corpulent (SHR/NDmcr-cp) rats were divided into 4 groups then fed a normal diet with or without phycocyanin (2500-, 5000-, or 10,000-mg/kg diet) for 25 weeks. At 34 weeks of age, although systolic blood pressure was not significantly different among groups, phycocyanin-fed groups exhibited a dose-dependent decrease in blood pressure. Serum levels of adiponectin and messenger RNA levels of adiponectin and CCAAT/enhancer-binding protein α in the adipose tissue of rats fed diets containing phycocyanin tended to be higher than those of rats fed a normal diet, but the differences were not statistically significant. Immunohistochemistry analysis showed a significant and positive correlation between aortic endothelial nitric oxide synthase (eNOS) expression levels, a downstream target of the adiponectin receptor, and serum adiponectin levels, although there were no significant differences in eNOS expression among groups. There was also no significant correlation between eNOS expression levels and systolic blood pressure. These results suggest that long-term administration of phycocyanin may ameliorate systemic blood pressure by enhancing eNOS expression in aorta that is stimulated by adiponectin. Phycocyanin may be beneficial for preventing endothelial dysfunction-related diseases in metabolic syndrome.

  18. 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

  19. Study of Adiponectin Level in Diabetic Adolescent Girls in Relation to Glycemic Control and Complication of Diabetes

    PubMed Central

    Dayem, Soha M. Abd El; Nazif, Hayam K.; EI-Kader, Mona Abd; El-Tawil, Maha

    2015-01-01

    AIM: To study the relation between adiponectin level with glycemic control and complication of diabetes. PATIENTS AND METHODS: The study included 40 female adolescent type 1 diabetic patients and 40 healthy volunteers of the same age and sex. Blood sample was taken for assessment of glycosylated hemoglobin, lipid profile and adiponectine. Urine sample was taken for assessment of albumin/creatinine ratio. RESULTS: Diabetic patients had a significantly higher diastolic blood pressure, triglyceride, total cholesterol, LDL and adiponectin than controls. Patients with diabetes complication had a significant lower BMI and HDL. On the other hand, they had higher disease duration, total cholesterol, HbA1, albumin/creatinine ratio and adiponectin. Patients with microalbuminuria had a lower BMI, higher disease duration, diastolic blood pressure and adiponectin. Patients with diabetic retinopathy had higher disease duration, insulin dose, HbA1, microalbuminuria and adiponectin. Adiponectin in diabetic patients had a significant negative correlation with BMI and positive correlation with systolic blood pressure and microlabuminuria. CONCLUSION: Serum adiponectin level is high in adolescent type 1 diabetic girls. It can be used as a predictor of diabetes complications rather than a sensitive biochemical marker for glycemic control. PMID:27275296

  20. Comparison of metabolic profile and adiponectin level with pioglitazone versus voglibose in patients with type-2 diabetes mellitus associated with metabolic syndrome.

    PubMed

    Fujitaka, Keisuke; Otani, Hajime; Jo, Fusakazu; Jo, Hiromi; Nomura, Emiko; Iwasaki, Masayoshi; Nishikawa, Mitsushige; Iwasaka, Toshiji

    2011-01-01

    Type 2 diabetes mellitus (T2DM) associated with metabolic syndrome (MetS) represents a high risk of cardiovascular disease. We compared the effect of early intervention with pioglitazone versus voglibose on physical and metabolic profiles and serum adiponectin level in patients with T2DM associated with MetS. Sixty patients who were diagnosed for the first time as T2DM associated with MetS were analyzed for insulin sensitivity, lipid profile, serum adiponectin and systemic inflammation. Those patients were randomly assigned to oral pioglitazone group (n = 30) or voglibose group (n = 30) in addition to conventional diet and exercise training. Body mass index and waist circumference did not change in the pioglitazone group, whereas these physical parameters significantly decreased in the voglibose group during a 6-month follow-up period. However, glycosylated hemoglobin, fasting plasma glucose, and HOMA-IR more significantly decreased in the pioglitazone group. The level of serum adiponectin especially high-molecular weight adiponectin markedly increased in the pioglitazone group. Moreover, high sensitive CRP significantly decreased only in the pioglitazone group. These results suggest that voglibose is superior in improving obesity, while pioglitazone is superior in ameliorating insulin sensitivity and increasing serum adiponectin in patients with an early stage of T2DM associated with MetS.

  1. Coculture with primary visceral rat adipocytes from control but not streptozotocin-induced diabetic animals increases glucose uptake in rat skeletal muscle cells: role of adiponectin.

    PubMed

    Vu, Vivian; Kim, Wi; Fang, Xiangping; Liu, Yuan-Tao; Xu, Aimin; Sweeney, Gary

    2007-09-01

    We developed a coculture system comprising primary rat adipocytes and L6 rat skeletal muscle cells to allow investigation of the effects of physiologically relevant mixtures of adipokines. We observed that coculture, or adipocyte-conditioned media, increased glucose uptake in muscle cells. An adipokine that could potentially mediate this effect is adiponectin, and we demonstrated that small interfering RNA-mediated knockdown of adiponectin receptor-2 in muscle cells reduced the uptake of glucose upon coculture with primary rat adipocytes. Analysis of coculture media by ELISA indicated total adiponectin concentration of up to 1 microg/ml, and Western blotting and gel filtration analysis demonstrated that the adipokine profile was hexamer greater than high molecular weight much greater than trimer. We used the streptozotocin-induced rat model of diabetes and found that high-molecular-weight adiponectin levels decreased in comparison with control animals and this correlated with the fact that diabetic rat-derived primary adipocytes in coculture did not stimulate glucose uptake to the same extent as control adipocytes. Coculture induced phosphorylation of AMP-activated protein kinase (T172) and interestingly also insulin receptor substrate-1 (Y612) and Akt (T308 & S473), which could be attenuated after adiponectin receptor-2-small interfering RNA treatment. In summary, we believe that this coculture system represents an excellent model to study the effects of primary adipocyte-derived adipokine mixtures on skeletal muscle metabolism, and here we have established that in the context of physiologically relevant mixtures of adipokines, adiponectin may be an important determinant of positive cross talk between adipocytes and skeletal muscle.

  2. Mendelian Randomization Studies Do Not Support a Causal Role for Reduced Circulating Adiponectin Levels in Insulin Resistance and Type 2 Diabetes

    PubMed Central

    Yaghootkar, Hanieh; Lamina, Claudia; Scott, Robert A.; Dastani, Zari; Hivert, Marie-France; Warren, Liling L.; Stancáková, Alena; Buxbaum, Sarah G.; Lyytikäinen, Leo-Pekka; Henneman, Peter; Wu, Ying; Cheung, Chloe Y.Y.; Pankow, James S.; Jackson, Anne U.; Gustafsson, Stefan; Zhao, Jing Hua; Ballantyne, Christie M.; Xie, Weijia; Bergman, Richard N.; Boehnke, Michael; el Bouazzaoui, Fatiha; Collins, Francis S.; Dunn, Sandra H.; Dupuis, Josee; Forouhi, Nita G.; Gillson, Christopher; Hattersley, Andrew T.; Hong, Jaeyoung; Kähönen, Mika; Kuusisto, Johanna; Kedenko, Lyudmyla; Kronenberg, Florian; Doria, Alessandro; Assimes, Themistocles L.; Ferrannini, Ele; Hansen, Torben; Hao, Ke; Häring, Hans; Knowles, Joshua W.; Lindgren, Cecilia M.; Nolan, John J.; Paananen, Jussi; Pedersen, Oluf; Quertermous, Thomas; Smith, Ulf; Lehtimäki, Terho; Liu, Ching-Ti; Loos, Ruth J.F.; McCarthy, Mark I.; Morris, Andrew D.; Vasan, Ramachandran S.; Spector, Tim D.; Teslovich, Tanya M.; Tuomilehto, Jaakko; van Dijk, Ko Willems; Viikari, Jorma S.; Zhu, Na; Langenberg, Claudia; Ingelsson, Erik; Semple, Robert K.; Sinaiko, Alan R.; Palmer, Colin N.A.; Walker, Mark; Lam, Karen S.L.; Paulweber, Bernhard; Mohlke, Karen L.; van Duijn, Cornelia; Raitakari, Olli T.; Bidulescu, Aurelian; Wareham, Nick J.; Laakso, Markku; Waterworth, Dawn M.; Lawlor, Debbie A.; Meigs, James B.; Richards, J. Brent; Frayling, Timothy M.

    2013-01-01

    Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic variants at the ADIPOQ gene as instruments to calculate a regression slope between adiponectin levels and metabolic traits (up to 31,000 individuals) and a combination of instrumental variables and summary statistics–based genetic risk scores to test the associations with gold-standard measures of insulin sensitivity (2,969 individuals) and type 2 diabetes (15,960 case subjects and 64,731 control subjects). In conventional regression analyses, a 1-SD decrease in adiponectin levels was correlated with a 0.31-SD (95% CI 0.26–0.35) increase in fasting insulin, a 0.34-SD (0.30–0.38) decrease in insulin sensitivity, and a type 2 diabetes odds ratio (OR) of 1.75 (1.47–2.13). The instrumental variable analysis revealed no evidence of a causal association between genetically lower circulating adiponectin and higher fasting insulin (0.02 SD; 95% CI −0.07 to 0.11; N = 29,771), nominal evidence of a causal relationship with lower insulin sensitivity (−0.20 SD; 95% CI −0.38 to −0.02; N = 1,860), and no evidence of a relationship with type 2 diabetes (OR 0.94; 95% CI 0.75–1.19; N = 2,777 case subjects and 13,011 control subjects). Using the ADIPOQ summary statistics genetic risk scores, we found no evidence of an association between adiponectin-lowering alleles and insulin sensitivity (effect per weighted adiponectin-lowering allele: −0.03 SD; 95% CI −0.07 to 0.01; N = 2,969) or type 2 diabetes (OR per weighted adiponectin-lowering allele: 0.99; 95% CI 0.95–1.04; 15,960 case subjects vs. 64,731 control subjects). These results do not provide any consistent evidence that interventions aimed at increasing adiponectin levels will improve insulin sensitivity or risk of

  3. In contrast to matrix metalloproteinases, serum adiponectin concentrations increase after radioiodine treatment of thyrotoxicosis

    PubMed Central

    2012-01-01

    Background Matrix metalloproteinases (MMPs), together with their tissue inhibitors (TIMPs), remodel extracellular matrix under physiological and pathological conditions and are implicated in pathogenesis of cardiovascular diseases, cancer and in chronic inflammation. We have endeavoured to assess whether concentrations of MMPs, TIMPs, and anti-inflammatory adiponectin are altered by pharmacological treatment of acute thyrotoxicosis or by radioiodine therapy (RIT). Material and methods We measured serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, and adiponectin, TSH, free T4 (FT4) and free T3 (FT3) in 15 patients (4 males), age (years) 51.8±15.3 (mean±SD) with hyperthyroidism treated with thiamazole (Group 1) and in 20 subjects (2 males), treated for thyrotoxicosis with radioiodine, age 52.3±12.4 (Group 2), where blood samples were taken before RIT, visit 1 (V1), seven days post RIT, visit 2 (V2), and two to three months post RIT, visit 3 (V3). Results In Group 1 there was no significant change in concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2 or adiponectin, despite a fall in FT4 and FT3 (8.74±4.79 pg/ml vs 3.54±2.40 pg/ml, for FT3, and 4.48 ±2.21 ng/ml vs 1.02±1.07 ng/ml, for FT4, p<0.001). In Group 2 RIT did not cause any acute change in serum MMP-2, MMP-9, TIMP-1 and TIMP-2 or adiponectin (V1 vs V2). However, there was a significant increase in serum adiponectin [from 15201±8860 ng/ml (V1) to 19373±8657 ng/ml (at V3), p<0.05], and TIMP-2 at V3 [from 129±45 ng/ml (V1) to 149±38 ng/ml (V3), p<0.01]. There was no significant change MMP-2, MMP-9 and TIMP-1 between V1 and V3. There was a decrease in FT4 and FT3 from 24.4±15.4 pmol/l (V1) to 14.7±10.6 pmol/l (V3), and from 10.0±5.65 (V1) to 6.1±4.8 pmol/l (V2), p<0.01, for FT4 and FT3, respectively. Conclusions Radioiodine therapy of thyrotoxicosis does not alter serum MMP-2, MMP-9 or TIMP-1 concentrations either acutely or after about three months of observation. An increase in serum adiponectin

  4. Ghrelin, leptin, adiponectin, and resistin levels in sleep apnea syndrome: Role of obesity

    PubMed Central

    Ursavas, Ahmet; Ilcol, Yesim Ozarda; Nalci, Nazan; Karadag, Mehmet; Ege, Ercument

    2010-01-01

    AIM: The aim of this study was to investigate the relationship among plasma leptin, ghrelin, adiponectin, resistin levels, and obstructive sleep apnea syndrome (OSAS). METHODS: Fifty-five consecutive newly diagnosed OSAS patients and 15 age-matched nonapneic controls were enrolled in this study. After sleep study between 8:00 AM and 9:00 AM on the morning, venous blood was obtained in the fasting state to measure ghrelin and adipokines. RESULTS: Serum ghrelin levels of OSAS group were significantly (P < 0.05) higher than those of the control group. No significant difference was noted in the levels of leptin, adiponectin, and resistin in OSAS group when compared to controls. There was a significant positive correlation between ghrelin and apnea–hypopnea index (AHI) (r = 0.237, P < 0.05) or the Epworth sleepiness scale (ESS) (r = 0.28, P < 0.05). There was also a significant positive correlation between leptin and body mass index (r = 0.592, P < 0.0001). No significant correlation was observed between leptin, adiponectin, resistin, and any polysomnographic parameters. CONCLUSION: Our findings demonstrated that serum ghrelin levels were higher in OSAS patients than those of control group and correlated with AHI and ESS. Further studies are needed to clarify the complex relation among OSAS, obesity, adipokines, and ghrelin. PMID:20835311

  5. Enhanced nutrition improves growth and increases blood adiponectin concentrations in very low birth weight infants

    PubMed Central

    Blakstad, Elin W.; Moltu, Sissel J.; Nakstad, Britt; Veierød, Marit B.; Strømmen, Kenneth; Júlíusson, Pétur B.; Almaas, Astrid N.; Rønnestad, Arild E.; Brække, Kristin; Drevon, Christian A.; Iversen, Per O.

    2016-01-01

    Background Adequate nutrient supply is essential for optimal postnatal growth in very low birth weight (VLBW, birth weight<1,500 g) infants. Early growth may influence the risk of metabolic syndrome later in life. Objective To evaluate growth and blood metabolic markers (adiponectin, leptin, and insulin-like growth factor-1 (IGF-1)) in VLBW infants participating in a randomized nutritional intervention study. Design Fifty VLBW infants were randomized to an enhanced nutrient supply or a standard nutrient supply. Thirty-seven infants were evaluated with growth measurements until 2 years corrected age (CA). Metabolic markers were measured at birth and 5 months CA. Results Weight gain and head growth were different in the two groups from birth to 2 years CA (weight gain: pinteraction=0.006; head growth: pinteraction=0.002). The intervention group improved their growth z-scores after birth, whereas the control group had a pronounced decline, followed by an increase and caught up with the intervention group after discharge. At 5 months CA, adiponectin concentrations were higher in the intervention group and correlated with weight gain before term (r=0.35) and nutrient supply (0.35≤r≤0.45). Leptin concentrations correlated with weight gain after term and IGF-1 concentrations with length growth before and after term and head growth after term (0.36≤r≤0.53). Conclusion Enhanced nutrient supply improved early postnatal growth and may have prevented rapid catch-up growth later in infancy. Adiponectin concentration at 5 months CA was higher in the intervention group and correlated positively with early weight gain and nutrient supply. Early nutrition and growth may affect metabolic markers in infancy. Clinical Trial Registration (ClinicalTrials.gov) no.: NCT01103219 PMID:27914187

  6. Downregulation of GPR83 in the hypothalamic preoptic area reduces core body temperature and elevates circulating levels of adiponectin.

    PubMed

    Dubins, Jeffrey S; Sanchez-Alavez, Manuel; Zhukov, Victor; Sanchez-Gonzalez, Alejandro; Moroncini, Gianluca; Carvajal-Gonzalez, Santos; Hadcock, John R; Bartfai, Tamas; Conti, Bruno

    2012-10-01

    The G protein-coupled receptor 83 (GPR83) was recently demonstrated in warm sensitive neurons (WSN) of the hypothalamic preoptic area (POA) that participate in temperature homeostasis. Thus, we investigated whether GPR83 may have a role in regulating core body temperature (CBT) by reducing its expression in the POA. Dissipation of energy in the form of heat is the primary mode of energy expenditure in mammals and can ultimately affect energy homeostasis. Thus, we also measured the level of important regulators of metabolism. Downregulation of GPR83 was obtained by lentiviral short-hairpin RNAs (shGPR83) vectors designed and selected for their ability to reduce GPR83 levels in vitro. Mice received POA injection of shGPR83 or non-silencing vectors and were monitored for CBT, motor activity, food intake body weight and circulating levels of IGF-1, insulin, leptin and adiponectin. Down-regulation of GPR83 in the POA resulted in a small (0.15°C) but significant reduction of CBT during the dark/active cycle of the day. Temperature reduction was followed by increased body weight gain independent of caloric intake. shGPR83 mice also had increased level of circulating adiponectin (31916±952 pg/mL vs. 23474±1507 pg/mL, P<.01) while no change was observed for insulin, IGF-1 or leptin. GPR83 may participate in central thermoregulation and the central control of circulating adiponectin. Further work is required to determine how GPR83 can affect POA WSN and what are the long term metabolic consequences of its down-regulation.

  7. Effects of Rosuvastatin Alone or in Combination with Omega-3 Fatty Acid on Adiponectin Levels and Cardiometabolic Profile

    PubMed Central

    Al-Kuraishy, Hayder M.; Al-Gareeb, Ali I.

    2016-01-01

    Background: Adiponectin is an important adipocyte-related protein that has been postulated to participate in prevention of the development of metabolic syndrome. The relationship between adiponectin serum levels and risk of coronary artery disease (CAD) has been widely investigated and remains controversial. The aim of the present study was to evaluate the effects of rosuvastatin and/or omega-3 fatty acid on adiponectin serum levels in patients with insulin resistance (IR) and CAD. Patients and Methods: This study involved 87 patients with CADs and IR of different etiology, the patients were divided into three groups; 24 patients on treatment with rosuvastatin, 22 patients on treatment with omega-3 fatty acid, 23 patients on treatment with omega-3 fatty acid and rosuvastatin, 18 patients were not previously or currently treated with either rosuvastatin or omega-3 fatty acid, those regarded as control patients. Anthropometric measures, adiponectin serum levels, and other biochemical parameters were assessed in each treated group. Results: Rosuvastatin therapy leads to a significant elevation in adiponectin serum levels from 4.1 ± 0.99 ng/mL to 6.76 ± 1.03 ng/mL compared to control P < 0.01. Omega-3 fatty acid therapy leads to a significant elevation in adiponectin serum levels from 4.1 ± 0.99 ng/mL to 6.11 ± 1.29 ng/mL compared to control P < 0.01. Rosuvastatin plus omega-3 fatty acid therapy lead to a significant elevation in adiponectin serum levels from 4.1 ± 0.99 ng/mL to 7.99 ± 1.76 ng/mL compared to control P < 0.01. Conclusions: Rosuvastatin and/or omega-3 fatty acid lead to significant cardiometabolic protection through an increment in adiponectin serum levels. PMID:28104968

  8. Leptin and adiponectin in the female life course.

    PubMed

    Lecke, S B; Morsch, D M; Spritzer, P M

    2011-05-01

    Adipose tissue secretes a variety of adipokines, including leptin and adiponectin, which are involved in endocrine processes regulating glucose and fatty metabolism, energy expenditure, inflammatory response, immunity, cardiovascular function, and reproduction. The present article describes the fluctuations in circulating leptin and adiponectin as well as their patterns of secretion in women from birth to menopause. During pregnancy, leptin and adiponectin seem to act in an autocrine/paracrine fashion in the placenta and adipose tissue, playing a role in the maternal-fetal interface and contributing to glucose metabolism and fetal development. In newborns, adiponectin levels are two to three times higher than in adults. Full-term newborns have significantly higher leptin and adiponectin levels than preterms, whereas small-for-gestational-age infants have lower levels of these adipokines than adequate-for-gestational-age newborns. However, with weight gain, leptin concentrations increase significantly. Children between 5 and 8 years of age experience an increase in leptin and a decrease in adiponectin regardless of body mass index, with a reversal of the newborn pattern for adiponectin: plasma adiponectin levels at age five are inversely correlated with percentage of body fat. In puberty, leptin plays a role in the regulation of menstrual cycles. In adults, it has been suggested that obese individuals exhibit both leptin resistance and decreased serum adiponectin levels. In conclusion, a progressive increase in adiposity throughout life seems to influence the relationship between leptin and adiponectin in women.

  9. Adiponectin levels predict prediabetes risk: the Pathobiology of Prediabetes in A Biracial Cohort (POP-ABC) study

    PubMed Central

    Jiang, Yunna; Owei, Ibiye; Wan, Jim; Ebenibo, Sotonte; Dagogo-Jack, Samuel

    2016-01-01

    Background Adiponectin levels display ethnic disparities, and are inversely associated with the risk of type 2 diabetes (T2DM). However, the association of adiponectin with prediabetes risk in diverse populations has not been well-studied. Here, we assessed baseline adiponectin levels in relation to incident prediabetes in a longitudinal biracial cohort. Research design and methods The Pathobiology of Prediabetes in A Biracial Cohort study followed non-diabetic offspring of parents with T2DM for the occurrence of prediabetes, defined as impaired fasting glucose and/or impaired glucose tolerance. Assessments at enrollment and during follow-up included a 75 g oral glucose tolerance test, anthropometry, biochemistries (including fasting insulin and adiponectin levels), insulin sensitivity and insulin secretion. Logistic regression was used to evaluate the contribution of adiponectin to risk of progression to prediabetes. Results Among the 333 study participants (mean (SD) age 44.2 (10.6) year), 151(45.3%) were white and 182 (54.8%) were black. During approximately 5.5 (mean 2.62) years of follow-up, 110 participants (33%) progressed to prediabetes (N=100) or T2DM (N=10), and 223 participants (67%) were non-progressors. The mean cohort adiponectin level was 9.41+5.30 μg/mL (range 3.1–45.8 μg/mL); values were higher in women than men (10.3+5.67 μg/mL vs 7.27+3.41 μg/mL, p<0.0001) and in white than black offspring (10.7+5.44 μg/mL vs 8.34+4.95 μg/mL, p<0.0001). Adiponectin levels correlated inversely with adiposity and glycemia, and positively with insulin sensitivity and high-density lipoprotein cholesterol levels. Baseline adiponectin strongly predicted incident prediabetes: the HR for prediabetes per 1 SD (approximately 5 μg/mL) higher baseline adiponectin was 0.48 (95% CI 0.27 to 0.86, p=0.013). Conclusions Among healthy white and black adults with parental history of T2DM, adiponectin level is a powerful risk marker of incident prediabetes

  10. Adiponectin Enhances Mouse Fetal Fat Deposition

    PubMed Central

    Qiao, Liping; Yoo, Hyung sun; Madon, Alysha; Kinney, Brice; Hay, William W.; Shao, Jianhua

    2012-01-01

    Maternal obesity increases offspring birth weight and susceptibility to obesity. Adiponectin is an adipocyte-secreted hormone with a prominent function in maintaining energy homeostasis. In contrast to adults, neonatal blood adiponectin levels are positively correlated with anthropometric parameters of adiposity. This study was designed to investigate the role of adiponectin in maternal obesityenhanced fetal fat deposition. By using high-fat diet–induced obese mouse models, our study showed that maternal obesity increased fetal fat tissue mass, with a significant elevation in fetal blood adiponectin. However, adiponectin gene knockout (Adipoq−/−) attenuated maternal obesity-induced high fetal fat tissue mass. We further studied the effects of fetal adiponectin on fetal fat deposition by using a cross breeding approach to create Adipoq−/+ and Adipoq−/− offspring, whereas maternal adiponectin was null. Adipoq−/+ offspring had more fat tissue mass at both birth and adulthood. Significantly high levels of lipogenic genes, such as sterol regulatory element–binding protein 1c and fatty acid synthase, were detected in the livers of Adipoq−/+ fetuses. In addition, expression of genes for placental fatty acid transport was significantly increased in Adipoq−/+ fetuses. Together, our study indicates that adiponectin enhances fetal fat deposition and plays an important role in maternal obesity-induced high birth weight. PMID:22872236

  11. Reappraisal of effects of serum chemerin and adiponectin levels and nutritional status on cardiovascular outcomes in prevalent hemodialysis patients

    PubMed Central

    Chen, Hung-Yuan; Chiu, Yen-Lin; Hsu, Shih-Ping; Pai, Mei-Fen; Yang, Ju-Yeh; Wu, Hon-Yen; Peng, Yu-Sen

    2016-01-01

    Although chemerin, an adipokine, increases the cardiovascular (CV) risk in obese people, it is associated with a survival advantage in incident hemodialysis (HD) patients. We explored the potential effects of chemerin on CV outcomes in prevalent HD patients. This prospective study included 343 prevalent HD patients. The composite outcome was the occurrence of CV events and death during follow-up. We used multivariate Cox regression analysis to test the predictive power of different chemerin and adiponectin levels and geriatric nutritional risk index (GNRI) for the outcomes. HD patients with higher chemerin levels (≥211.4 ng/mL) had a lower risk of CV events (adjusted hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.41–0.98) and composite CV outcome (adjusted HR, 0.67; 95% CI, 0.45–0.99) than those with lower chemerin levels (<211.4 ng/mL). When evaluating CV outcomes, we identified an interaction between chemerin levels and GNRI, but not between chemerin and adiponectin levels. The findings remained robust in the sensitivity analysis. Thus, in prevalent HD patients with negligible residual renal function, higher chemerin levels predict more favourable CV outcomes. PMID:27667092

  12. Low plasma adiponectin level, white blood cell count and Helicobacter pylori titre independently predict abnormal pancreatic beta-cell function.

    PubMed

    So, Wing-Yee; Tong, Peter C; Ko, Gary T; Ma, Ronald C; Ozaki, Risa; Kong, Alice P; Yang, Xilin; Ho, Chung-Shun; Lam, Christopher C; Chan, Juliana C

    2009-11-01

    Adiponectin is an adipocytokine with insulin sensitizing effect while chronic inflammation damages pancreatic beta-cells leading to reduced insulin response. We aimed to prove the hypothesis that adiponectin levels and inflammatory markers (white blood cell counts [WCC], Helicobacter pylori [HP] titers, high sensitivity C-reactive protein [hs-CRP]) may interact to affect risk of diabetes. We studied 288 Chinese men (age-median: 41.0 years, IQR: 35.3-46.0 years) being recruited from the community in Hong Kong. The mean adiponectin level was 5.39+/-2.81 microg/ml and 40.9% (n=107) had low adiponectin level (<4 microg/ml). On multiple regression analysis, adiponectin was negatively associated with diabetes, HOMA insulin resistance top quartile, plasma glucose (PG) and 2h insulin; and positively associated with HOMA insulin sensitivity index. WCC was independently associated with PG and 15' insulin, and negatively associated with HOMA insulin sensitivity top quartile. HP titre was associated with 30' PG level and diabetes. hs-CRP did not enter the multivariable model. In conclusion, adiponectin, WCC and HP titer are independent predictors for hyperglycemia and reduced insulin sensitivity in Chinese men. These findings may explain the high risk for diabetes in Chinese population despite their relatively low adiposity.

  13. Circulating adiponectin levels and risk of endometrial cancer: Systematic review and meta-analysis.

    PubMed

    Li, Zhi-Jun; Yang, Xue-Ling; Yao, Yan; Han, Wei-Qing; Li, B O

    2016-06-01

    Previous epidemiological studies have presented conflicting results regarding associations between circulating adiponectin (APN) levels and the risk of endometrial cancer. Thus a meta-analysis was performed to investigate the association between these factors. Multiple electronic sources, including PubMed, SpringerLink and Google Scholar databases were searched to identify relevant studies for the present meta-analysis. All of the selected studies examined the correlation between circulating APN levels and endometrial cancer. The standardized mean difference (SMD) and 95% confidence intervals (CIs) were estimated and pooled using meta-analysis methods. Overall, 18 case-control studies met the inclusion criteria. A total of 5,692 participants and 2,337 cases of endometrial cancer were included in this meta-analysis. The SMD of the pooled analysis (95% CI) were -1.96 (-2.60, -1.31), P=0.000. When the cancer grades were compared, the APN values were not significantly different between the grades of endometrial cancer [G1 vs. G3, 1.02 (-0.68, 2.72), P>0.05; G1 vs. G2, 0.34 (-0.86, 1.54), P>0.05]. However, there was a significant association between high APN levels and postmenopausal endometrial cancer cases with an SMD (95% CI) of -2.27 (-4.36, -0.18) and P<0.05, however, no association was observed in premenopausal endometrial cancer cases with an SMD (95% CI) of -1.52 (-3.49, 0.45) and P>0.05. The low circulating APN level increases the risk of endometrial cancer, whereas the high APN level decreases this risk in postmenopausal women. Circulating APN as simple biomarkers may be a promising tool for the prevention, early diagnosis and disease monitoring of endometrial cancer.

  14. Circulating adiponectin levels and risk of endometrial cancer: Systematic review and meta-analysis

    PubMed Central

    LI, ZHI-JUN; YANG, XUE-LING; YAO, YAN; HAN, WEI-QING; LI, BO

    2016-01-01

    Previous epidemiological studies have presented conflicting results regarding associations between circulating adiponectin (APN) levels and the risk of endometrial cancer. Thus a meta-analysis was performed to investigate the association between these factors. Multiple electronic sources, including PubMed, SpringerLink and Google Scholar databases were searched to identify relevant studies for the present meta-analysis. All of the selected studies examined the correlation between circulating APN levels and endometrial cancer. The standardized mean difference (SMD) and 95% confidence intervals (CIs) were estimated and pooled using meta-analysis methods. Overall, 18 case-control studies met the inclusion criteria. A total of 5,692 participants and 2,337 cases of endometrial cancer were included in this meta-analysis. The SMD of the pooled analysis (95% CI) were −1.96 (−2.60, −1.31), P=0.000. When the cancer grades were compared, the APN values were not significantly different between the grades of endometrial cancer [G1 vs. G3, 1.02 (−0.68, 2.72), P>0.05; G1 vs. G2, 0.34 (−0.86, 1.54), P>0.05]. However, there was a significant association between high APN levels and postmenopausal endometrial cancer cases with an SMD (95% CI) of −2.27 (−4.36, −0.18) and P<0.05, however, no association was observed in premenopausal endometrial cancer cases with an SMD (95% CI) of −1.52 (−3.49, 0.45) and P>0.05. The low circulating APN level increases the risk of endometrial cancer, whereas the high APN level decreases this risk in postmenopausal women. Circulating APN as simple biomarkers may be a promising tool for the prevention, early diagnosis and disease monitoring of endometrial cancer. PMID:27284314

  15. Visceral Fat Area and Serum Adiponectin Level Predict the Development of Metabolic Syndrome in a Community-Based Asymptomatic Population

    PubMed Central

    Cho, Jae-Young; Lee, Seung Hun; Park, Jae Hyoung; Hong, Soon Jun; Yu, Cheol Woong; Lim, Do-Sun

    2017-01-01

    Background Although it has been demonstrated that visceral adipose tissue content and serum levels of adiponectin are associated with metabolic syndrome, their predictive potential for the development of metabolic syndrome remains to be elucidated. Methods We studied 1,130 participants of the Seoul Metabolic Syndrome cohort. A total of 337 subjects without metabolic syndrome underwent the follow-up evaluation and finally analyzed. Visceral fat area (VFA) was measured using dual bioelectrical impedance analysis. We compared the 1-year incidence rate of metabolic syndrome among four different groups: Group 1 (high adiponectin level and low VFA), Group 2 (low adiponectin level and low VFA), Group 3 (high adiponectin level and high VFA) and Group 4 (low adiponectin level and high VFA). Results Median follow-up duration was 17 months. Cut-off points of adiponectin level and VFA for metabolic syndrome were 7.34 ng/ml and 84 cm2 for men, and 12.55 and 58 cm2 ng/ml for women, respectively. The incidence of metabolic syndrome was the highest in Group 4 (Group 1; 16.47%, Group 2; 22.08%, Group 3; 25%, and Group 4; 46.15%, p<0.001). Adjusted logistic regression analyses for metabolic syndrome prediction demonstrated that Group 4 exhibited the highest odds ratio compared with Group 1 (4.918 [2.05–11.795]), which was predominantly affected by waist circumference and serum triglyceride levels. Notably, triglyceride/high-density lipoprotein cholesterol (TG/HDL) ratio was significantly higher in Group 4 (p = 0.017). Conclusion Incidence rate of metabolic syndrome was the highest in subjects with low serum adiponectin levels and high visceral fat area. Higher TG/HDL ratio in these subjects suggested insulin resistance may contribute to the development of metabolic syndrome. PMID:28046037

  16. Circulating Adiponectin and Risk of Endometrial Cancer

    PubMed Central

    Zheng, Qiaoli; Wu, Haijian; Cao, Jiang

    2015-01-01

    Background Adiponectin is an insulin-sensitizing hormone produced by adipocytes. It has been suggested to be involved in endometrial tumorigenesis. Published data have shown inconsistent results for the association between circulating adiponectin levels and endometrial cancer. In this study, we conducted a meta-analysis to evaluate the predictive value of circulating adiponectin levels on the development of endometrial cancer. Methods PubMed, Embase, ISI web of knowledge, and Cochrane databases were searched for all eligible studies, and the summary relative risk (SRR) was calculated. Additionally, we performed dose-response analysis with eight eligible studies. Results A total of 1,955 cases and 3,458 controls from 12 studies were included. The SRR for the ‘highest’ vs ‘lowest’ adiponectin levels indicated high adiponectin level reduced the risk of endometrial cancer [SRR = 0.40, 95% confidence interval (CI), 0.33–0.66]. Results from the subgroup analyses were consistent with the overall analysis. The SRR for each 1 µg/ml increase of adiponectin indicated a 3% reduction in endometrial cancer risk (95% CI: 2%–4%), and a 14% reduction for each increase of 5 µg/ml (95% CI: 9%–19%). No evidence of publication bias was found. Conclusions This meta-analysis demonstrates that low level of circulating adiponectin is a risk factor for endometrial cancer. PMID:26030130

  17. Associations between single-nucleotide polymorphisms of ADIPOQ, serum adiponectin and increased type 2 diabetes mellitus risk in Bahraini individuals.

    PubMed

    Al Hannan, F A; O'Farrell, P A; Morgan, M P; Tighe, O; Culligan, K G

    2016-11-02

    This study aimed to estimate the frequency of the SNPs (+45T>G and +276G>T) genotypes and investigate the association between the two SNPs and adiponectin concentration, metabolic parameters and risk of T2DM in the Bahraini population. We genotyped the two ADIPOQ SNPs in 140 unrelated T2DM patients and 66 nondiabetic controls using the polymerase chain reaction-restriction fragment length polymorphism assay. Lipid profile was measured by enzymatic methods. Total serum adiponectin levels were measured by immunoassay. T2DM patients had reduced adiponectin levels compared with controls. +45T>G was more prevalent in patients than controls. The rare G allele of +45T>G occurred more frequently than the common T allele in T2DM patients compared with controls, and was associated with lower serum adiponectin levels. There was no significant difference in allele and genotype frequencies of +276G>T between type T2DM patients and controls. There was no association between both SNPs and metabolic parameters.

  18. Dietary Supplementation with ω-3 PUFA Increases Adiponectin and Attenuates Ventricular Remodeling and Dysfunction with Pressure Overload

    PubMed Central

    Duda, Monika K.; O'Shea, Karen M.; Lei, Biao; Barrows, Brian R.; Azimzadeh, Agnes M.; McElfresh, Tracy E.; Hoit, Brian D.; Kop, Willem J.; Stanley, William C.

    2009-01-01

    Objective Epidemiological studies suggest that consumption of ω-3 polyunsaturated fatty acids (ω-3 PUFA) decreases the risk of heart failure. We assessed the effects of dietary supplementation with ω-3 PUFA from fish oil on the response of the left ventricle (LV) to arterial pressure overload. Methods Male Wistar rats were fed a standard chow or a ω-3 PUFA-supplemented diet. After 1 week rats underwent abdominal aortic banding or sham surgery (n=9-12/group). LV function was assessed by echocardiography after 8 weeks. In addition, we studied the effect of ω-3 PUFA on the cardioprotective adipocyte-derived hormone adiponectin, which may alter the pro-growth serine-threonine kinase Akt. Results Banding increased LV mass to a greater extent with the standard chow (31%) than with ω-3 PUFA (18%). LV end diastolic and systolic volumes were increased by 19% and 105% with standard chow, respectively, but were unchanged with ω-3 PUFA. The expression of adiponectin was up-regulated in adipose tissue, and the plasma adiponectin concentration was significantly elevated. Treatment with ω-3 PUFA increased total Akt protein expression in the heart, but decreased the fraction of Akt in the active phosphorylated form, and thus did not alter the amount of active phospho-Akt. Conclusion Dietary supplementation with ω-3 PUFA attenuated pressure overload-induced LV dysfunction, which was associated with elevated plasma adiponectin. PMID:17643403

  19. 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.

  20. Adiponectin, leptin, and yoga practice.

    PubMed

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

    2012-12-05

    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.

  1. 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

  2. Delayed liver regeneration after partial hepatectomy in adiponectin knockout mice

    SciTech Connect

    Ezaki, Hisao; Yoshida, Yuichi; Saji, Yukiko; Takemura, Takayo; Fukushima, Juichi; Matsumoto, Hitoshi; Kamada, Yoshihiro; Wada, Akira; Igura, Takumi; Kihara, Shinji; Funahashi, Tohru; Shimomura, Iichiro; Tamura, Shinji; Kiso, Shinichi Hayashi, Norio

    2009-01-02

    We previously demonstrated that adiponectin has anti-fibrogenic and anti-inflammatory effects in the liver of mouse models of various liver diseases. However, its role in liver regeneration remains unclear. The aim of this study was to determine the role of adiponectin in liver regeneration. We assessed liver regeneration after partial hepatectomy in wild-type (WT) and adiponectin knockout (KO) mice. We analyzed DNA replication and various signaling pathways involved in cell proliferation and metabolism. Adiponectin KO mice exhibited delayed DNA replication and increased lipid accumulation in the regenerating liver. The expression levels of peroxisome proliferator-activated receptor (PPAR) {alpha} and carnitine palmitoyltransferase-1 (CPT-1), a key enzyme in mitochondrial fatty acid oxidation, were decreased in adiponectin KO mice, suggesting possible contribution of altered fat metabolism to these phenomena. Collectively, the present results highlight a new role for adiponectin in the process of liver regeneration.

  3. Smoking Habits and Neuropeptides: Adiponectin, Brain-derived Neurotrophic Factor, and Leptin Levels

    PubMed Central

    Won, Yong Lim; Ko, Kyung Sun; Roh, Ji won

    2014-01-01

    This study aimed to identify changes in the level of neuropeptides among current smokers, former smokers, and individuals who had never smoked, and how smoking habits affect obesity and metabolic syndrome (MetS). Neuropeptide levels, anthropometric parameters, and metabolic syndrome diagnostic indices were determined among male workers; 117 of these had never smoked, whereas 58 and 198 were former and current smokers, respectively. The total sample comprised 373 male workers. The results obtained from anthropometric measurements showed that current smokers attained significantly lower body weight, body mass index, waist circumference, and abdominal fat thickness values than former smokers and those who had never smoked. Current smokers’ eating habits proved worse than those of non-smokers and individuals who had never smoked. The level of brain-derived neurotrophic factor (BDNF) in the neuropeptides in the case of former smokers was 23.6 ± 9.2 pg/ml, higher than that of current smokers (20.4 ± 6.1) and individuals who had never smoked (22.4 ± 5.8) (F = 6.520, p = 0.002). The level of adiponectin among former smokers was somewhat lower than that of current smokers, whereas leptin levels were higher among former smokers than current smokers; these results were not statistically significant. A relationship was found between adiponectin and triglyceride among non-smokers (odds ratio = 0.660, β value = −0.416, p < 0.01) and smokers (odds ratio = 0.827, β value = −0.190, p < 0.05). Further, waist circumference among non-smokers (odds ratio = 1.622, β value = 0.483, p < 0.001) and smokers (odds ratio = 1.895, β value = 0.639, p < 0.001) was associated with leptin. It was concluded that cigarette smoking leads to an imbalance of energy expenditure and appetite by changing the concentration of neuropeptides such as adiponectin, BDNF, leptin, and hsCRP, and influences food intake, body weight, the body mass index, blood pressure, and abdominal fat, which are

  4. Adiponectin levels in south Indian children with type 1 diabetes mellitus and nondiabetic children and its correlation with anthropometry and glycemic control.

    PubMed

    Solomon, J Ritchie Sharon; Varadarajan, Poovazhagi; Varadarajan, V Poovazhagi

    2013-09-01

    Studies have reported high adiponectin levels in children with type 1 diabetes mellitus (T1DM). Adiponectin has been found to have anti-atherogenic action and other protective functions. We wanted to estimate adiponectin level in south Indian T1DM children and compare it with that of non-diabetic children and study its correlation with anthropometry and glycemic status. Sixty children with T1DM and forty non-diabetic children of age less than 15 years were analysed. Mean adiponectin level was higher in T1DM group than in non diabetic group (p < 0.001) irrespective of the age group or sex. Negative correlation was observed between SFT- triceps and adiponectin in diabetic and control group. Multiple regression coefficient analysis of various parameters showed SFT- triceps as a statistically significant predictor of adiponectin level (p = 0.001). We conclude that, children with T1DM had higher adiponectin level than non-diabetic children. Low SFT- triceps measuremet may be a predictor of higher adiponectin level.

  5. 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.

  6. 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

  7. Serum Zinc and Adiponectin Levels in Patients with Polycystic Ovary Syndrome, Adjusted for Anthropometric, Biochemical, Dietary Intake, and Physical Activity Measures.

    PubMed

    Mazloomi, Sahar; Alizadeh, Narges; Aminzare, Majid; Niroomand, Soudabeh; Mousavi, Seyedeh Neda

    2017-02-03

    Previous studies have shown that serum zinc and adiponectin levels are associated with insulin resistance in the polycystic ovary syndrome (PCOS) patients. But there is no study to evaluate serum zinc and adiponectin levels as predictor markers of PCOS, adjusted for anthropometric, biochemical, dietary intake, and physical activity measures. Ninety-one new PCOS cases (based on the Rotterdam criteria) and 85 healthy control women participated and individually matched based on age. Food intake of all participants obtained by the food frequency and physical activity level was assessed by the International Physical Activity Questionnaires. Serum glucose, lipid profile, androgens, insulin, adiponectin, and zinc concentrations were measured at the fasting state. Weight, BMI, waist circumference, and body fat, as well as serum levels of DHEAS, insulin, TG, LDL cholesterol (LDL.C), homeostasis model assessment of insulin resistance (HOMA-IR), and LH/FSH ratio, were significantly higher in the PCOS compared with those of the healthy control women. Serum levels of zinc and adiponectin were significantly lower in the PCOS than those of the healthy control women. Results of the logistic regression model showed significant effects of adiponectin, zinc, and LH/FSH ratio on the PCOS, adjusted for anthropometric and biochemical measures (p < 0.05). In the present study, serum level of zinc had significant correlation with adiponectin in the PCOS patients, and serum levels of zinc, adiponectin, and LH/FSH ratio had significant effects on the PCOS occurrence.

  8. Inhibition of smooth muscle cell proliferation by adiponectin requires proteolytic conversion to its globular form.

    PubMed

    Fuerst, Melissa; Taylor, Carla G; Wright, Brenda; Tworek, Leslee; Zahradka, Peter

    2012-10-01

    Accelerated atherosclerosis is the primary cardiovascular manifestation of diabetes and correlates inversely with levels of circulating adiponectin, an anti-atherosclerotic adipokine that declines in diabetes. We therefore initiated a study to examine the mechanisms by which adiponectin, a hormone released from adipose tissue, influences the proliferation of vascular smooth muscle cells (SMCs). Addition of adiponectin to quiescent porcine coronary artery SMCs increased both protein and DNA synthesis and concurrently activated ERK1/2 and Akt. By contrast, globular adiponectin, a truncated form of this protein, exhibited anti-mitogenic properties as indicated by the inhibition of protein and DNA synthesis in SMCs stimulated with platelet-derived growth factor (PDGF). Whereas globular adiponectin did not stimulate growth-related signal transduction pathways, it was able to block the PDGF-dependent phosphorylation of eukaryotic elongation factor 2 kinase, a regulator of protein synthesis. Proteolysis of adiponectin with trypsin, which produces globular adiponectin, reversed the growth-stimulating actions of the undigested protein. As the existence of globular adiponectin remains controversial, western blotting was used to establish its presence in rat serum. We found that globular adiponectin was detectable in rat serum, but this result was not obtained with all antibodies. The contrasting properties of adiponectin and its globular form with respect to SMC proliferation suggest that protection against atherosclerosis may therefore be mediated, in part, by the level of globular adiponectin.

  9. Reduced-energy cranberry juice increases folic acid and adiponectin and reduces homocysteine and oxidative stress in patients with the metabolic syndrome.

    PubMed

    Simão, Tathiana Name Colado; Lozovoy, Marcell Alysson Batisti; Simão, Andréa Name Colado; Oliveira, Sayonara Rangel; Venturini, Danielle; Morimoto, Helena Kaminami; Miglioranza, Lúcia Helena Silva; Dichi, Isaias

    2013-11-01

    The metabolic syndrome (MetS) comprises pathological conditions that include insulin resistance, arterial hypertension, visceral adiposity and dyslipidaemia, which favour the development of CVD. Some reports have shown that cranberry ingestion reduces cardiovascular risk factors. However, few studies have evaluated the effect of this fruit in subjects with the MetS. The objective of the present study was to assess the effect of reduced-energy cranberry juice consumption on metabolic and inflammatory biomarkers in patients with the MetS, and to verify the effects of cranberry juice concomitantly on homocysteine and adiponectin levels in patients with the MetS. For this purpose, fifty-six individuals with the MetS were selected and divided into two groups: control group (n 36) and cranberry-treated group (n 20). After consuming reduced-energy cranberry juice (0·7 litres/d) containing 0·4mg folic acid for 60 d, the cranberry-treated group showed an increase in adiponectin (P=0·010) and folic acid (P=0·033) and a decrease in homocysteine (P<0·001) in relation to baseline values and also in comparison with the controls (P<0·05). There was no significant change in the pro-inflammatory cytokines TNF-a, IL-1 and IL-6. In relation to oxidative stress measurements, decreased (P<0·05) lipoperoxidation and protein oxidation levels assessed by advanced oxidation protein products were found in the cranberry-treated group when compared with the control group. In conclusion, the consumption of cranberry juice for 60 d was able to improve some cardiovascular risk factors. The present data reinforce the importance of the inverse association between homocysteine and adiponectin and the need for more specifically designed studies on MetS patients.

  10. Impact of dyslipidemic components of metabolic syndrome, adiponectin levels, and anti-diabetes medications on malondialdehyde-modified low-density lipoprotein levels in statin-treated diabetes patients with coronary artery disease

    PubMed Central

    2013-01-01

    Background A residual risk of cardiovascular disease tends to persist despite standard prevention therapy with statins. This may stem partly from increased oxidized low-density lipoprotein (LDL) levels. However, how oxidized LDL can be further reduced beyond statin therapy in high-risk diabetes patients remains unclear. We aimed to clarify the clinical factors associated with oxidized LDL levels in statin-treated high-risk diabetes patients. Methods This cross-sectional observational study included 210 diabetes patients with coronary artery diseases (CAD) who were treated with statins. We determined serum malondialdehyde-modified LDL (MDA-LDL), LDL cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (TG), remnant lipoprotein cholesterol, hemoglobin (Hb) A1c, adiponectin, and C-reactive protein (CRP) levels and investigated the factors influencing the MDA-LDL level. Results In univariate analysis, the MDA-LDL level was significantly correlated with LDL cholesterol (p < 0.0001), TG (p < 0.0001), HDL cholesterol (p = 0.017), and adiponectin (p = 0.001) levels but not with age, body mass index, waist circumference, blood pressure, or HbA1c levels. Even after adjusting for the LDL cholesterol level, the correlations between the MDA-LDL level and the TG, HDL cholesterol, and adiponectin levels were still significant. Among these significant factors, multivariate analysis revealed that the MDA-LDL level was independently associated with the LDL cholesterol, TG, and HDL cholesterol but not with adiponectin levels. The MDA-LDL level was also significantly associated with the CRP level (p = 0.014) and the remnant lipoprotein cholesterol level (p < 0.0001) independently of the LDL cholesterol level. The number of metabolic syndrome (MS) components was significantly associated with the MDA-LDL/LDL cholesterol ratio (p < 0.0001). Furthermore, the use of metformin and α-glucosidase inhibitors was inversely associated with high MDA

  11. The Relationship between Adiponectin and Breast Cancer

    PubMed Central

    Erbay, Burcu; Yılmaz, Tonguç Utku; Eraldemir, Ceyla; Üren, Nihal; Tiryaki, Çağrı; Ergül, Emel; Utkan, Zafer

    2016-01-01

    Objective Breast cancer is the most common type of cancer in women worldwide. It is indicated that increased body mass index elevates the risk of developing breast cancer, worsens prognosis, and decreases survival. Several polymorphisms of adiponectin have been shown to affect serum levels of adiponectin and their association with breast cancer. The aim of this study was to investigate the relationship between the adiponectin 45T/G and 276 G/T gene polymorphism and breast cancer in the East Marmara region. Materials and Methods A case-control study was performed in 97 patients with breast cancer and 101 controls in East Marmara in order to evaluate the prevalence of adiponectin gene polymorphism at positions 45 and 276. Patients with familial breast cancer and those who had received chemotherapy or radiotherapy were excluded from the study. Adiponectin gene polymorphisms were investigated using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). Results Adiponectin 45T/G gene genotype frequencies of TT, TG, and GG were 61.9%, 37.1%, and 1% in patients with breast cancer, and 67.3%, 30.7%, and 2% in the control group, respectively. Adiponectin 276G/T gene genotype frequencies of GG, GT, and TT were 45.4%, 45.4%, and 9.3% in patients with breast cancer and 55.4%, 39.6%, and 5.0% in the control group, respectively. Conclusion Our study showed that adiponectin 45T/G and 276 G/T gene polymorphism is not associated with breast cancer risk in patients from the East Marmara region.

  12. Acute effects of a single warm-water bath on serum adiponectin and leptin levels in healthy men: A pilot study

    NASA Astrophysics Data System (ADS)

    Shimodozono, Megumi; Matsumoto, Shuji; Ninomiya, Koji; Miyata, Ryuji; Ogata, Atsuko; Etoh, Seiji; Watanabe, Satoshi; Kawahira, Kazumi

    2012-09-01

    To preliminarily assess the acute effects of a single warm -water bath (WWB) on serum adipokine activity, we measured serum adiponectin, leptin and other metabolic profiles before, immediately after and 30 minutes after WWB in seven healthy male volunteers (mean age, 39.7 ± 6.0 years; mean body mass index, 21.6 ± 1.8 kg/m2). The subjects were immersed in tap water at 41°C for 10 minutes. Two weeks later, the same subjects underwent a single WWB with a bath additive that included inorganic salts and carbon dioxide (WWB with ISCO2) by the same protocol as for the first WWB. Leptin levels significantly increased immediately after WWB with tap water and ISCO2 (both P < 0.05), and remained significantly higher than those at baseline even 30 minutes after WWB with tap water ( P < 0.05). Adiponectin levels showed a slight, but not significant, increase both immediately after and 30 minutes after WWB with tap water or ISCO2. Some parameters, such as serum total cholesterol, red blood cell count, hemoglobin and hematocrit significantly increased immediately after WWB with tap water or ISCO2 (all P < 0.05), but they all returned to the baseline levels 30 minutes after bathing under both conditions. The sublingual temperature rose significantly after 10 minutes of WWB with tap water (0.96 ± 0.16°C relative to baseline, P < 0.01) and after the same duration of WWB with ISCO2 (1.24 ± 0.34°C relative to baseline, P < 0.01). These findings suggest that a single WWB at 41°C for 10 minutes may modulate leptin and adiponectin profiles in healthy men.

  13. Influence of androgens on circulating adiponectin in male and female rodents.

    PubMed

    Yarrow, Joshua F; Beggs, Luke A; Conover, Christine F; McCoy, Sean C; Beck, Darren T; Borst, Stephen E

    2012-01-01

    Several endocrine factors, including sex-steroid hormones are known to influence adiponectin secretion. Our purpose was to evaluate the influence of testosterone and of the synthetic non-aromatizable/non-5α reducible androgen 17β-hydroxyestra-4,9,11-trien-3-one (trenbolone) on circulating adiponectin and adiponectin protein expression within visceral fat. Young male and female F344 rats underwent sham surgery (SHAM), gonadectomy (GX), or GX plus supraphysiologic testosterone-enanthate (TE) administration. Total circulating adiponectin was 39% higher in intact SHAM females than SHAM males (p<0.05). GX increased total adiponectin by 29-34% in both sexes (p<0.05), while TE reduced adiponectin to concentrations that were 46-53% below respective SHAMs (p≤0.001) and ablated the difference in adiponectin between sexes. No differences in high molecular weight (HMW) adiponectin were observed between sexes or treatments. Adiponectin concentrations were highly and negatively associated with serum testosterone (males: r = -0.746 and females: r = -0.742, p≤0.001); however, no association was present between adiponectin and estradiol. In separate experiments, trenbolone-enanthate (TREN) prevented the GX-induced increase in serum adiponectin (p≤0.001) in young animals, with Low-dose TREN restoring adiponectin to the level of SHAMs and higher doses of TREN reducing adiponectin to below SHAM concentrations (p≤0.001). Similarly, TREN reduced adiponectin protein expression within visceral fat (p<0.05). In adult GX males, Low-dose TREN also reduced total adiponectin and visceral fat mass to a similar magnitude as TE, while increasing serum HMW adiponectin above SHAM and GX animals (p<0.05). Serum adiponectin was positively associated with visceral fat mass in young (r = 0.596, p≤0.001) and adult animals (r = 0.657, p≤0.001). Our results indicate that androgens reduce circulating total adiponectin concentrations in a dose-dependent manner, while maintaining HMW

  14. Induction of human adiponectin gene transcription by telmisartan, angiotensin receptor blocker, independently on PPAR-{gamma} activation

    SciTech Connect

    Moriuchi, Akie ||. E-mail: f1195@cc.nagasaki-u-ac.jp; Shimamura, Mika; Kita, Atsushi; Kuwahara, Hironaga; Satoh, Tsuyoshi; Satoh, Tsuyoshi; Fujishima, Keiichiro; Fukushima, Keiko |; Hayakawa, Takao; Mizuguchi, Hiroyuki; Nagayama, Yuji; Kawasaki, Eiji

    2007-05-18

    Adiponectin, an adipose tissue-specific plasma protein, has been shown to ameliorate insulin resistance and inhibit the process of atherosclerosis. Recently, several reports have stated that angiotensin type 1 receptor blockers (ARBs), increase adiponectin plasma level, and ameliorate insulin resistance. Telmisartan, a subclass of ARBs, has been shown to be a partial agonist of the peroxisome proliferator-activated receptor (PPAR)-{gamma}, and to increase the plasma adiponectin level. However, the transcriptional regulation of the human adiponectin gene by telmisartan has not been determined yet. To elucidate the effect of telmisartan on adiponectin, the stimulatory regulation of human adiponectin gene by telmisartan was investigated in 3T3-L1 adipocytes, utilizing adenovirus-mediated luciferase reporter gene-transferring technique. This study indicates that telmisartan may stimulate adiponectin transcription independent of PPAR-{gamma}.

  15. Empirical Characteristics of Family-Based Linkage to a Complex Trait: the ADIPOQ Region and Adiponectin Levels

    PubMed Central

    Hellwege, Jacklyn N.; Palmer, Nicholette D.; Brown, W. Mark; Ziegler, Julie T.; An, S. Sandy; Guo, Xiuqing; Chen, Y.-D. Ida; Taylor, Kent; Hawkins, Gregory A.; Ng, Maggie C.Y.; Speliotes, Elizabeth K.; Lorenzo, Carlos; Norris, Jill M.; Rotter, Jerome I.; Wagenknecht, Lynne E.; Langefeld, Carl D.; Bowden, Donald W.

    2014-01-01

    We previously identified a low frequency (1.1%) coding variant (G45R; rs200573126) in the adiponectin gene (ADIPOQ) which was the basis for a multipoint microsatellite linkage signal (LOD=8.2) for plasma adiponectin levels in Hispanic families. We have empirically evaluated the ability of data from targeted common variants, exome chip genotyping, and genome-wide association study (GWAS) data to detect linkage and association to adiponectin protein levels at this locus. Simple two-point linkage and association analyses were performed in 88 Hispanic families (1150 individuals) using 10,958 SNPs on chromosome 3. Approaches were compared for their ability to map the functional variant, G45R, which was strongly linked (two-point LOD=20.98) and powerfully associated (p-value=8.1×10−50). Over 450 SNPs within a broad 61 Mb interval around rs200573126 showed nominal evidence of linkage (LOD>3) but only four other SNPs in this region were associated with p-values<1.0×10−4. When G45R was accounted for, the maximum LOD score across the interval dropped to 4.39 and the best p-value was 1.1×10−5. Linked and/or associated variants ranged in frequency (0.0018 to 0.50) and type (coding, non-coding) and had little detectable linkage disequilibrium with rs200573126 (r2<0.20). In addition, the two-point linkage approach empirically outperformed multipoint microsatellite and multipoint SNP analysis. In the absence of data for rs200573126, family-based linkage analysis using a moderately dense SNP dataset, including both common and low frequency variants, resulted in stronger evidence for an adiponectin locus than association data alone. Thus, linkage analysis can be a useful tool to facilitate identification of high impact genetic variants. PMID:25447270

  16. 4-Hydroxynonenal differentially regulates adiponectin gene expression and secretion via activating PPARγ and accelerating ubiquitin–proteasome degradation

    PubMed Central

    Wanga, Zhigang; Dou, Xiaobing; Gu, Dongfang; Shen, Chen; Yao, Tong; Nguyen, Van; Braunschweig, Carol; Song, Zhenyuan

    2011-01-01

    Although well-established, the underlying mechanisms involved in obesity-related plasma adiponectin decline remain elusive. Oxidative stress is associated with obesity and insulin resistance and considered to contribute to the progression toward obesity-related metabolic disorders. In this study, we investigated the effects of 4-hydroxynonenal (4-HNE), the most abundant lipid peroxidation end product, on adiponectin production and its potential implication in obesity-related adiponectin decrease. Long-term high-fat diet feeding led to obesity in mouse, accompanied by decreased plasma adiponectin and increased adipose tissue 4-HNE content. Exposure of adipocytes to exogenous 4-HNE resulted in decreased adiponectin secretion in a dose-dependent manner, which was consistent with significantly decreased intracellular adiponectin protein abundance. In contrast, adiponectin gene expression was significantly elevated by 4-HNE treatment, which was concomitant with increased peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression and transactivity. The effect was abolished by T0070907, a PPAR-γ antagonist, suggesting that PPAR-γ activation plays a critical role in this process. To gain insight into mechanisms involved in adiponectin protein decrease, we examined the effects of 4-HNE on adiponectin protein degradation. Cycloheximide (CHX)-chase assay revealed that 4-HNE exposure accelerated adiponectin protein degradation, which was prevented by MG132, a potent proteasome inhibitor. Immunoprecipitation assay showed that 4-HNE exposure increased ubiquitinated adiponectin protein levels. These data altogether indicated that 4-HNE enhanced adiponectin protein degradation via ubiquitin–proteasome system. Finally, we demonstrated that supplementation of HF diet with betaine, an antioxidant and methyl donor, alleviated high-fat-induced adipose tissue 4-HNE increase and attenuated plasma adiponectin decline. Taken together, our findings suggest that the lipid

  17. 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

  18. Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts

    SciTech Connect

    Kitahara, Kanako; Kusunoki, Natsuko; Kakiuchi, Terutaka; Suguro, Toru; Kawai, Shinichi

    2009-01-09

    The adipokines are linked not only to metabolic regulation, but also to immune responses. Adiponectin, but not leptin or resistin induced interleukin-8 production from rheumatoid synovial fibroblasts (RSF). The culture supernatant of RSF treated with adiponectin induced chemotaxis, although adiponectin itself had no such effect. Addition of antibody against adiponectin, and inhibition of adiponectin receptor gene decreased adiponectin-induced IL-8 production. Nuclear translocation of nuclear factor-kappa B was increased by adiponectin. The induction of interleukin-8 was inhibited by mitogen-activated protein kinase inhibitors. These findings suggest that adiponectin contributes to the pathogenesis of rheumatoid arthritis.

  19. Protective effects of berberine on high fat-induced kidney damage by increasing serum adiponectin and promoting insulin sensitivity.

    PubMed

    Wu, Ueyue; Cha, Ying; Huang, Xinmei; Liu, Jun; Chen, Zaoping; Wang, Fang; Xu, Jiong; Sheng, Li; Ding, Heyuan

    2015-01-01

    Berberine (BBR) has been reported in several studies in cell and animal models. However, the mechanism of actions is not fully understood. The present study was therefore aimed to explore the effects of berberine on insulin sensitivity and kidney damage in a high fat diet rat model. Impaired glucose tolerance rats induced by injection of berberine while fed with high fat laboratory chow. After rats were treated for 4 weeks, OGTT and IPITT were determined. Mass and PAS were used to study the kidney tissue. ELISA was used to detect the protein concentration of CRP and TNF-α. Western blot was used to detect the proteins adiponectin, adipoR1, adipoR2 and p-AMPK expression level. These encouraging findings suggest that berberine has excellent pharmacological potential to prevent kidney damage.

  20. Effect of monomeric adiponectin on cardiac function and perfusion in anesthetized pig.

    PubMed

    Grossini, Elena; Prodam, Flavia; Walker, Gillian Elisabeth; Sigaudo, Lorenzo; Farruggio, Serena; Bellofatto, Kevin; Marotta, Patrizia; Molinari, Claudio; Mary, David; Bona, Gianni; Vacca, Giovanni

    2014-07-01

    Adiponectin, the most abundant adipokine released by adipose tissue, appears to play an important role in the regulation of vascular endothelial and cardiac function. To date, however, the physiological effects of human monomeric adiponectin on the coronary vasculature and myocardial systo-diastolic function, as well as on parasympathetic/sympathetic involvement and nitric oxide (NO) release, have not yet been investigated. Thus, we planned to determine the primary in vivo effects of human monomeric adiponectin on coronary blood flow and cardiac contractility/relaxation and the related role of autonomic nervous system, adiponectin receptors, and NO. In 30 anesthetized pigs, human monomeric adiponectin was infused into the left anterior descending coronary artery at constant heart rate and arterial blood pressure, and the effects on coronary blood flow, left ventricular systo-diastolic function, myocardial oxygen metabolism, and NO release were examined. The mechanisms of the observed hemodynamic responses were also analyzed by repeating the highest dose of human monomeric adiponectin infusion after autonomic nervous system and NO blockade, and after specific adiponectin 1 receptor antagonist administration. Intracoronary human monomeric adiponectin caused dose-related increases of coronary blood flow and cardiac function. Those effects were accompanied by increased coronary NO release and coronary adiponectin levels. Moreover, the vascular effects of the peptide were prevented by blockade of β2-adrenoceptors and NO synthase, whereas all effects of human monomeric adiponectin were prevented by adiponectin 1 receptor inhibitor. In conclusion, human monomeric adiponectin primarily increased coronary blood flow and cardiac systo-diastolic function through the involvement of specific receptors, β2-adrenoceptors, and NO release.

  1. Evaluation of salivary adiponectin profile in obese patients.

    PubMed

    Nigro, E; Piombino, P; Scudiero, O; Monaco, M L; Schettino, P; Chambery, A; Daniele, A

    2015-01-01

    Obesity is a chronic inflammatory disease significantly risen worldwide, especially among children. Adipokines, secreted from adipose tissue, are hormones involved in various cellular processes such as energy metabolism and inflammation. Among the others, adiponectin is gaining increasing interest for its insulin-sentitizing, anti-atherogenic and anti-inflammatory properties. This adipokine undergoes different post-translational modifications, after which it circulates as oligomers of high, medium and low molecular weight (HMW, MMW, LMW); HMW are the most biologically active oligomers. Serum adiponectin levels as well as the amount of its oligomers are inversely correlated to BMI and closely associated with obesity and related diseases. In this study, we analyzed total adiponectin expression and its oligomeric profile in saliva samples from 27 obese compared to 27 age- and sex-matched controls. Moreover, we compared adiponectin oligomerization between serum and saliva samples. The analysis of the different adiponectin oligomers reveals a slightly higher expression of total, HMW and LMW salivary adiponectin in obese patients compared to controls. Finally, FPLC analysis evidenced that HMW oligomers in saliva have a higher molecular weight than in serum confirming the presence of more complex oligomers in saliva, previously identified as super HMW (S-HMW). Saliva is considered a potential source of novel biomarkers for the diagnosis of metabolic disorders. The assessment of total adiponectin and its oligomeric profiles in saliva samples may represent a promising biological marker for the analysis of metabolic diseases.

  2. Integral role of PTP1B in adiponectin-mediated inhibition of oncogenic actions of leptin in breast carcinogenesis.

    PubMed

    Taliaferro-Smith, LaTonia; Nagalingam, Arumugam; Knight, Brandi Brandon; Oberlick, Elaine; Saxena, Neeraj K; Sharma, Dipali

    2013-01-01

    The molecular effects of obesity are mediated by alterations in the levels of adipocytokines. High leptin level associated with obese state is a major cause of breast cancer progression and metastasis, whereas adiponectin is considered a "guardian angel adipocytokine" for its protective role against various obesity-related pathogenesis including breast cancer. In the present study, investigating the role of adiponectin as a potential inhibitor of leptin, we show that adiponectin treatment inhibits leptin-induced clonogenicity and anchorage-independent growth. Leptin-stimulated migration and invasion of breast cancer cells is also effectively inhibited by adiponectin. Analyses of the underlying molecular mechanisms reveal that adiponectin suppresses activation of two canonical signaling molecules of leptin signaling axis: extracellular signal-regulated kinase (ERK) and Akt. Pretreatment of breast cancer cells with adiponectin protects against leptin-induced activation of ERK and Akt. Adiponectin increases expression and activity of the physiological inhibitor of leptin signaling, protein tyrosine phosphatase 1B (PTP1B), which is found to be integral to leptin-antagonist function of adiponectin. Inhibition of PTP1B blocks adiponectin-mediated inhibition of leptin-induced breast cancer growth. Our in vivo studies show that adenovirus-mediated adiponectin treatment substantially reduces leptin-induced mammary tumorigenesis in nude mice. Exploring therapeutic strategies, we demonstrate that treatment of breast cancer cells with rosiglitazone results in increased adiponectin expression and inhibition of migration and invasion. Rosiglitazone treatment also inhibits leptin-induced growth of breast cancer cells. Taken together, these data show that adiponectin treatment can inhibit the oncogenic actions of leptin through blocking its downstream signaling molecules and raising adiponectin levels could be a rational therapeutic strategy for breast carcinoma in obese patients

  3. Adiponectin reduces ER stress-induced apoptosis through PPARα transcriptional regulation of ATF2 in mouse adipose

    PubMed Central

    Liu, Zhenjiang; Gan, Lu; Wu, Tianjiao; Feng, Fei; Luo, Dan; Gu, Huihui; Liu, Shimin; Sun, Chao

    2016-01-01

    Adiponectin is a cytokine produced predominantly by adipose tissue and correlates with glucose and lipid homeostasis. However, the effects of adiponectin on endoplasmic reticulum (ER) stress and apoptosis of adipose tissue remain elusive. In this study, we found that tunicamycin-induced ER stress increased serum free fatty acid (FFA) and impaired glucose tolerance, elevated the mRNA levels of GRP78, Chop, ATF2 and caspase 3, but reduced adiponectin mRNA level in white adipose tissue. Moreover, ER stress-triggered adipocyte apoptosis by increasing cellular FFA level and Ca2+ level. Further analysis revealed that adiponectin alleviated ER stress-induced adipocyte apoptosis by elevating peroxisome proliferator-activated receptor alpha (PPARα) mRNA level. Our data also confirmed that adiponectin reduced early apoptotic cells and blocked the mitochondrial apoptosis pathway by activating the AdipoR1/AMP-activated protein kinase (AMPK) signal pathway. In addition, PPARα bound to ATF2 promoter region and inhibited transcription of ATF2. The inhibition of adipocyte apoptosis by adiponectin was correlated with transcriptional suppression of ATF2. Furthermore, adiponectin inhibited ER stress-induced apoptosis by activating the AMPK/PKC pathway. In summary, our data demonstrate adiponectin inhibited ER stress and apoptosis of adipocyte in vivo and in vitro by activating the AMPK/PPARα/ATF2 pathway. Our study establishes that adiponectin is an important adipocytokine for preventing and treating obesity. PMID:27882945

  4. Effect of weight loss on high-molecular weight adiponectin in obese children.

    PubMed

    Martos-Moreno, Gabriel Á; Barrios, Vicente; Martínez, Guillermo; Hawkins, Federico; Argente, Jesús

    2010-12-01

    Our aim was to determine the influence of weight reduction on total (T-) and high-molecular weight (HMW-) adiponectin in obese (OB) prepubertal children. Seventy OB prepubertal white patients were followed for 18 months and studied after reducing their BMI by 1 (n = 51) and 2 standard deviation scores (SDS) (n = 21) under conservative treatment, and 6 months after achieving weight loss (n = 44). Body composition dual-energy X-ray absorptiometry (DXA) and serum levels of T- and HMW-adiponectin, resistin, leptin, leptin soluble receptor (sOB-R), tumoral necrosis factor-α and interleukin-6 were determined. The control group consisted of 61 healthy prepubertal children. At diagnosis T-adiponectin was higher (P < 0.01; confidence interval (+0.04) - (+0.15)) and HMW-adiponectin lower (P < 0.001; confidence interval (-0.45) - (-0.21)) in OB children than in controls. A reduction in body fat increased T- and HMW-adiponectin and sOB-R (all P < 0.001) and decreased leptin (P < 0.001) and interleukin-6 levels (P < 0.05). After 6 months of sustained weight reduction a decrease in tumoral necrosis factor-α (P < 0.01) occurred, whereas weight recovery increased leptin (P < 0.001) and decreased T-adiponectin (P < 0.05). HMW-adiponectin levels negatively correlated with homeostasis model assessment (HOMA) index and BMI in the whole cohort (both P < 0.001), as did T-adiponectin levels and HOMA index in OB patients (P < 0.01), but neither T- nor HMW-adiponectin correlated with body fat content (BFC) in OB children. We conclude that the impairment of T- and HMW-adiponectin levels in childhood obesity is different to that in elder OB patients, showing closer relationship with carbohydrate metabolism parameters than with BFC, but increasing their levels after weight loss and in association with metabolic improvement.

  5. Adiponectin, resistin and IL-6 plasma levels in subjects with diabetic foot and possible correlations with clinical variables and cardiovascular co-morbidity

    PubMed Central

    2010-01-01

    Introduction It is very suggestive that diabetic foot is characterized by a pronounced inflammatory reaction and the pathogenic significance of this inflammation has received little attention. On this basis the aim of our study was to evaluate plasma levels of adiponectin, resistin and IL-6 in subjects with diabetic foot in comparison with subjects without foot complications. Materials and methods We recruited 34 subjects with type 2 diabetes mellitus and foot ulceration hospitalized for every condition related to diabetic disease, but not for new vascular events (group A). As controls we recruited 37 patients with type 2 diabetes mellitus without foot ulceration (group B) hospitalized for every condition related to diabetic disease, but not for new vascular events. Adiponectin, Resistin and IL-6 serum levels were evaluated. Results Subjects of group A showed lower median plasma levels of adiponectin [7.7450 (4.47-12.17) μg/ml vs 8.480 (5.15-12.87) μg/ml], higher median plasma levels of IL-6 [3.21 (1.23-5.34) pg/ml vs 2.73 (1.24-3.97 pg/ml)] and of resistin [3.860 (2.96-6.29 ng/ml) vs 3.690 (2.,37-6.5 ng/ml)]. Conclusion Our study demonstrated that diabetic subjects with diabetic foot showed in comparison with diabetics without diabetic foot higher IL-6 and resistin plasma levels, lower adiponectin plasma levels. PMID:20836881

  6. Adiponectin in Fresh Frozen Plasma Contributes to Restoration of Vascular Barrier Function After Hemorrhagic Shock.

    PubMed

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

    2016-01-01

    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 with normal individuals, plasma adiponectin levels decreased to 49% in HS patients before 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 with 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.

  7. Adult Neurogenic and Antidepressant Effects of Adiponectin: A Potential Replacement for Exercise?

    PubMed

    Li, Ang; Yau, Suk-Yu; Machado, Sergio; Yuan, Ti-Fei; So, Kwok-Fai

    2015-01-01

    Physical exercise has long been recognized to benefit locomotor and cardiovascular systems. Although an increasing body of evidence also suggests it to be an effective non-medicinal remedy for mental disorders such as depression, the underlying mechanisms remain elusive. A recent study has demonstrated that increases of the adipocyte-secreted hormone adiponectin in the central nervous system following exercise may be responsible for these neuropsychological changes, including enhanced generation of neurons in the adult hippocampus, as well as mitigation of depressive severity. The present review introduces the previously-reported functions of adult hippocampal neurogenesis and adiponectin, and discusses the potential relevance of adiponectin signaling in exercise-induced neural changes. Revealing these novel biological effects of adiponectin in the brain may help hunt reliable biomarkers to better guide the anti-depressive therapy with exercise intervention; meanwhile, pharmaceutical agents that raise endogenous levels of adiponectin or mimic its biological effects might serve as a replacement for physical exercise.

  8. The Association of Chlamydia pneumonia and Helicobacter pylori IgG Seropositivity With Omentin-1, Visfatin and Adiponectin Levels in Postmenopausal Women.

    PubMed

    Ranjbar, Reza; Bolkheir, Alireza; Vahdat, Katayoun; Assadi, Majid; Darabi, Hossein; Nabipour, Iraj

    2016-12-01

    Some adipocytokines are cardioprotective or pro-inflammatory for cardiovascular system. Chronic infection with Chlamydia pneumoniae and Helicobacter pylori has been also considered as novel risk factors for atherosclerosis. The main aim of the current population-based study is to investigate the potential link between circulating adipocytokines and Chlamydia pneumoniae or Helicobacter pylori IgG seropositivities. A total of 250 healthy postmenopausal women who participated in a prospective cohort study were evaluated for IgG antibodies directed against C.pneumoniae and H. pylori. Omentin-1, visfatin, adiponectin, and high sensitivity C-reactive protein were measured by highly specific enzyme-linked immunosorbent assay methods. The prevalence of IgG antibodies against C. pneumoniae and H. pylori among the studied population was 20.4% (51 women) and 57.2% (143 women), respectively. There were no significant differences in adipocytokine levels between H. pylori IgG seropositive and H. pylori seronegative subjects. Similar results for visfatin and omentin-1 were found when C. pneumoniae IgG seropositive were compared with C. pneumoniae IgG seronegative subjects. However, in general linear model adjusted for age, body mass index and hs-CRP levels revealed significant difference between C. pneumoniae seropositive and C. pneumoniae seronegative subjects for circulating adiponectin. In conclusion, Chlamydia pneumoniae IgG seropositivity was associated with higher adiponectin levels in postmenopausal women. The elucidation of interaction mechanism of Chlamydia pneumoniae and a cardioprotective adipocytokine (adiponectin) will be useful in future therapeutic strategies.

  9. FTO rs 9939609 SNP Is Associated With Adiponectin and Leptin Levels and the Risk of Obesity in a Cohort of Romanian Children Population

    PubMed Central

    Duicu, Carmen; Mărginean, Cristina Oana; Voidăzan, Septimiu; Tripon, Florin; Bănescu, Claudia

    2016-01-01

    Abstract Obesity is a disorder with increasing frequency in children and adolescents, directly linked with various diseases. Variants in the FTO (fat mass and obesity-related) gene have been associated with body mass index and waist and hip circumferences in widespread populations. The aim of this case-control study was to assess if there is any association between FTO gene variants rs9939609, respectively, rs17817449 with anthropometric and metabolic biomarkers (fasting glucose, TC, HDL-cholesterol, LDL-cholesterol, triglycerides) and adipokines (adiponectin and leptin), in Romanian obese children. A total of 387 children, 201 obese and 186 nonobese individuals, were included in this prospective study. Genotyping of the FTO gene polymorphisms for all subjects was performed using the restriction fragment length polymorphism (PCR–RFLP) method. Significant associations were found between FTO rs9939609 single nucleotide polymorphism (SNP) and obesity. AA genotype carriers have a 2.02 times higher risk for obesity compared with AT+TT genotype carriers. Risk allele carriers of rs17817449 SNP had somewhat higher values of weight, body mass index, waist and hip circumference, total cholesterol, triglycerides, adiponectin, and fasting glucose. This study revealed the genetic association between rs9939609 SNP of FTO and obesity in a Romanian population, and to the authors’ knowledge, this is the first study to investigate this association in a Romanian population. This study also established that combined variant genotypes (AA/GG) of FTO rs9939609 /rs17817449 are strongly associated with several measures of adiposity (weight, BMI-SD, mid-upper arm circumference, tricipital skinfold thicknesses) and are also associated with total cholesterol, triglyceride, and LDL-cholesterol levels. PMID:27196486

  10. FTO rs 9939609 SNP Is Associated With Adiponectin and Leptin Levels and the Risk of Obesity in a Cohort of Romanian Children Population.

    PubMed

    Duicu, Carmen; Mărginean, Cristina Oana; Voidăzan, Septimiu; Tripon, Florin; Bănescu, Claudia

    2016-05-01

    Obesity is a disorder with increasing frequency in children and adolescents, directly linked with various diseases. Variants in the FTO (fat mass and obesity-related) gene have been associated with body mass index and waist and hip circumferences in widespread populations.The aim of this case-control study was to assess if there is any association between FTO gene variants rs9939609, respectively, rs17817449 with anthropometric and metabolic biomarkers (fasting glucose, TC, HDL-cholesterol, LDL-cholesterol, triglycerides) and adipokines (adiponectin and leptin), in Romanian obese children.A total of 387 children, 201 obese and 186 nonobese individuals, were included in this prospective study. Genotyping of the FTO gene polymorphisms for all subjects was performed using the restriction fragment length polymorphism (PCR-RFLP) method.Significant associations were found between FTO rs9939609 single nucleotide polymorphism (SNP) and obesity. AA genotype carriers have a 2.02 times higher risk for obesity compared with AT+TT genotype carriers. Risk allele carriers of rs17817449 SNP had somewhat higher values of weight, body mass index, waist and hip circumference, total cholesterol, triglycerides, adiponectin, and fasting glucose.This study revealed the genetic association between rs9939609 SNP of FTO and obesity in a Romanian population, and to the authors' knowledge, this is the first study to investigate this association in a Romanian population. This study also established that combined variant genotypes (AA/GG) of FTO rs9939609 /rs17817449 are strongly associated with several measures of adiposity (weight, BMI-SD, mid-upper arm circumference, tricipital skinfold thicknesses) and are also associated with total cholesterol, triglyceride, and LDL-cholesterol levels.

  11. Disulfide-Dependent Self-Assembly of Adiponectin Octadecamers from Trimers and Presence of Stable Octadecameric Adiponectin Lacking Disulfide Bonds In Vitro†

    PubMed Central

    Briggs, David B.; Jones, Christopher M.; Mashalidis, Ellene H.; Nuñez, Martha; Hausrath, Andrew C.; Wysocki, Vicki H.; Tsao, Tsu-Shuen

    2009-01-01

    Adiponectin is a circulating insulin-sensitizing hormone that homo-oligomerizes into trimers, hexamers, and higher molecular weight (HMW) species. Low levels of circulating HMW adiponectin appear to increase the risk for insulin resistance. Currently, assembly of adiponectin oligomers, and consequently mechanisms responsible for decreased HMW adiponectin in insulin resistance, are not well understood. In the work reported here, we analyzed the re-assembly of the most abundant HMW adiponectin species, the octadecamer, following its collapse to smaller oligomers in vitro. Purified bovine serum adiponectin octadecamer was treated with reducing agents at pH 5 to obtain trimers. These reduced trimers partially and spontaneously reassembled into octadecamers upon oxidative formation of disulfide bonds. Disulfide bonds appear to occupy a greater role in the process of oligomerization than in the structural stabilization of mature octadecamer. Stable octadecamers lacking virtually all disulfide bonds could be observed in abundance using native gel electrophoresis, dynamic light scattering, and collision-induced dissociation nano-electrospray ionization mass spectrometry. These findings indicate that while disulfide bonds help to maintain the mature octadecameric adiponectin structure, their more important function is to stabilize intermediates during the assembly of octadecamer. Adiponectin oligomerization must proceed through intermediates that are at least partially reduced. Accordingly, fully oxidized adiponectin hexamers failed to reassemble into octadecamers at a rate comparable to that of reduced trimers. As the findings from the present study are based on in vitro experiments, their in vivo relevance remains unclear. Nevertheless, they describe a redox environment-dependent model of adiponectin oligomerization that can be tested using cell-based approaches. PMID:19943704

  12. CRP and adiponectin and its oligomers in the metabolic syndrome: evaluation of new laboratory-based biomarkers.

    PubMed

    Devaraj, Sridevi; Swarbrick, Michael M; Singh, Uma; Adams-Huet, Beverley; Havel, Peter J; Jialal, Ishwarlal

    2008-05-01

    The metabolic syndrome (MetS) confers an increased risk for diabetes and cardiovascular disease. Although high-sensitive C-reactive protein (hsCRP) concentrations are higher and adiponectin concentrations lower in MetS, there is no reliable biochemical measure that can capture its various features. We evaluated whether hsCRP, adiponectin, or the ratio of adiponectin or its oligomers, especially the high-molecular-weight (HMW) oligomer, to hsCRP predict MetS in 123 subjects with MetS compared with that in 91 healthy control subjects. MetS subjects had significantly higher hsCRP levels and lower total adiponectin and oligomer levels relative to control subjects (P < .0001). The HMW/total adiponectin and adiponectin/CRP ratios were significantly lower in MetS subjects than control subjects (P < .005). The odds ratio (OR) of MetS using the 75th percentile cutoff for CRP was 3.8 (95% confidence interval [CI], 2.1-6.8) and equivalent to low total adiponectin (OR, 2.5; 95% CI, 1.3-4.5), its oligomers, or the adiponectin/ hsCRP ratio (OR, 2.6; 95% CI, 1.5, 4.8). Thus, measurements of CRP, adiponectin, or its oligomers provide robust biomarkers for predicting MetS.

  13. SSA 04-3 LEPTIN/ADIPONECTIN IN CARDIOMETABOLIC DISEASE.

    PubMed

    Lopez-Jaramillo, Patricio

    2016-09-01

    Cardiovascular diseases (CVD) are major causes of death and illness worldwide. In recent decades an increased prevalence of CVD mortality has been reported in low-medium income countries, which has been associated with changes in life styles, deficiencies in health systems and the persistence of social inequities.The metabolic syndrome comprises a cluster of cardiometabolic risk factors, with insulin resistance and increased adiposity as its central features. Identifying individuals with metabolic syndrome is important due to its association with an increased risk of coronary heart disease and type 2 diabetes mellitus (DM2). Attention has focused on the visceral adipose tissue production of cytokines (adipokines) in metabolic syndrome and DM2, as the levels of the anti-inflammatory adipokine adiponectin are decreased, while proinflammatory cytokines are elevated, creating a proinflammatory state associated with insulin resistance and endothelial dysfunction. We have give special attention to the role of the leptin/adiponectin ratio and we have demonstrated that in individuals with severe coronary artery disease, abdominal obesity (AO) was uniquely related to decreased plasma concentrations of adiponectin and increased leptin levels. Leptin/adiponectin imbalance was associated with increased waist circumference and a decreased vascular response to acetylcholine and increased vasoconstriction due to angiotensin II. Leptin and adiponectin have opposite effects on subclinical inflammation and insulin resistance. Leptin upregulates proinflammatory cytokines such as tumor necrosis factor-I and interleukin-6; these are associated with insulin resistance, DM2, and CVD. In contrast, adiponectin has anti-inflammatory properties and downregulates the expression and release of a number of proinflammatory immune mediators. Its concentrations are negatively regulated by the accumulation of visceral fat, and clinical studies implicate hypoadiponectinemia in the pathogenesis of DM

  14. Adiponectin oligomers and ectopic fat in liver and skeletal muscle in humans.

    PubMed

    Kantartzis, Konstantinos; Staiger, Harald; Machann, Jürgen; Schick, Fritz; Claussen, Claus D; Machicao, Fausto; Fritsche, Andreas; Häring, Hans-Ulrich; Stefan, Norbert

    2009-02-01

    We aimed at determining which circulating forms of the adipokine adiponectin that increases lipid oxidation in liver and skeletal muscle are related to ectopic fat in these depots in humans. Plasma total-, high-molecular weight (HMW)-, middle-molecular weight (MMW)-, and low-molecular weight (LMW) adiponectin were quantified by an enzyme-linked immunosorbent assay. Their relationships with liver- and intramyocellular fat, measured using (1)H magnetic resonance spectroscopy, were investigated in 54 whites without type 2 diabetes. Liver fat, adjusted for gender, age, and total body fat, was associated only with HMW adiponectin (r = -0.35, P = 0.012), but not with total-, MMW-, or LMW adiponectin. In addition, subjects with fatty liver (liver fat > or =5.56%, n = 15) had significantly lower HMW- (P = 0.04), but not total-, MMW-, or LMW adiponectin levels, compared to controls (n = 39). Similarly, intramyocellular fat correlated only with HMW (r = -0.32, P = 0.039), but not with the other circulating forms of adiponectin. These data indicate that, among circulating forms of adiponectin, HMW is strongly related to ectopic fat, thus possibly representing the form of adiponectin regulating lipid oxidation in liver and skeletal muscle.

  15. The role of leptin/adiponectin ratio in metabolic syndrome and diabetes.

    PubMed

    López-Jaramillo, Patricio; Gómez-Arbeláez, Diego; López-López, Jose; López-López, Cristina; Martínez-Ortega, Javier; Gómez-Rodríguez, Andrea; Triana-Cubillos, Stefany

    2014-04-01

    The metabolic syndrome comprises a cluster of cardiometabolic risk factors, with insulin resistance and adiposity as its central features. Identifying individuals with metabolic syndrome is important due to its association with an increased risk of coronary heart disease and type 2 diabetes mellitus. Attention has focused on the visceral adipose tissue production of cytokines (adipokines) in metabolic syndrome and type 2 diabetes mellitus, as the levels of the anti-inflammatory adipokine adiponectin are decreased, while proinflammatory cytokines are elevated, creating a proinflammatory state associated with insulin resistance and endothelial dysfunction. In this review, we will give special attention to the role of the leptin/adiponectin ratio. We have previously demonstrated that in individuals with severe coronary artery disease, abdominal obesity was uniquely related to decreased plasma concentrations of adiponectin and increased leptin levels. Leptin/adiponectin imbalance was associated with increased waist circumference and a decreased vascular response to acetylcholine and increased vasoconstriction due to angiotensin II. Leptin and adiponectin have opposite effects on subclinical inflammation and insulin resistance. Leptin upregulates proinflammatory cytokines such as tumor necrosis factor-α and interleukin-6; these are associated with insulin resistance and type 2 diabetes mellitus. In contrast, adiponectin has anti-inflammatory properties and downregulates the expression and release of a number of proinflammatory immune mediators. Therefore, it appears that interactions between angiotensin II and leptin/adiponectin imbalance may be important mediators of the elevated risk of developing type 2 diabetes mellitus and cardiovascular diseases associated with abdominal obesity.

  16. Role of leptin and adiponectin in insulin resistance.

    PubMed

    Yadav, Amita; Kataria, Megha A; Saini, Vandana; Yadav, Anil

    2013-02-18

    Adipose tissue is a major source of energy for the human body. It is also a source of major adipocytokines adiponectin and leptin. Insulin resistance is a condition in which insulin action is impaired in adipose tissue and is more strongly linked to intra-abdominal fat than to fat in other depots. The expression of adiponectin decreases with increase in the adiposity. Adiponectin mediates insulin-sensitizing effect through binding to its receptors AdipoR1 and AdipoR2, leading to activation of adenosine monophosphate dependent kinase (AMPK), PPAR-α, and presumably other yet-unknown signalling pathways. Weight loss significantly elevates plasma adiponectin levels. Reduction of adiponectin has been associated with insulin resistance, dyslipidemia, and atherosclerosis in humans. The other major adipokine is leptin. Leptin levels increase in obesity and subcutaneous fat has been a major determinant of circulating leptin levels. The leptin signal is transmitted by the Janus kinase, signal transducer and activator of transcription ((JAK-STAT) pathway. The net action of leptin is to inhibit appetite, stimulate thermogenesis, enhance fatty acid oxidation, decrease glucose, and reduce body weight and fat.

  17. Regional evidence of modulation of cardiac adiponectin level in dilated cardiomyopathy: pilot study in a porcine animal model

    PubMed Central

    2012-01-01

    Background The role of systemic and myocardial adiponectin (ADN) in dilated cardiomyopathy is still debated. We tested the regulation of both systemic and myocardial ADN and the relationship with AMP-activated protein kinase (AMPK) activity in a swine model of non-ischemic dilated cardiomyopathy. Methods and results Cardiac tissue was collected from seven instrumented adult male minipigs by pacing the left ventricular (LV) free wall (180 beats/min, 3 weeks), both from pacing (PS) and opposite sites (OS), and from five controls. Circulating ADN levels were inversely related to global and regional cardiac function. Myocardial ADN in PS was down-regulated compared to control (p < 0.05), yet ADN receptor 1 was significantly up-regulated (p < 0.05). No modifications of AMPK were observed in either region of the failing heart. Similarly, myocardial mRNA levels of PPARγ, PPARα, TNFα, iNOS were unchanged compared to controls. Conclusions Paradoxically, circulating ADN did not show any cardioprotective effect, confirming its role as negative prognostic biomarker of heart failure. Myocardial ADN was reduced in PS compared to control in an AMPK-independent fashion, suggesting the occurrence of novel mechanisms by which reduced cardiac ADN levels may regionally mediate the decline of cardiac function. PMID:23164042

  18. Adiponectin Signaling Regulates Lipid Production in Human Sebocytes

    PubMed Central

    Jung, Yu Ra; Lee, Jin-Hyup; Sohn, Kyung-Cheol; Lee, Young; Seo, Young-Joon; Kim, Chang-Deok; Lee, Jeung-Hoon; Hong, Seung-Phil; Seo, Seong-Jun; Kim, Seong-Jin; Im, Myung

    2017-01-01

    Adiponectin plays important roles in metabolic function, inflammation and multiple biological activities in various tissues. However, evidence for adiponectin signaling in sebaceous glands is lacking, and its role remains to be clarified. This study investigated the role of adiponectin in lipid production in sebaceous glands in an experimental study of human sebocytes. We demonstrated that human sebaceous glands in vivo and sebocytes in vitro express adiponectin receptor and that adiponectin increased cell proliferation. Moreover, based on a lipogenesis study using Oil Red O, Nile red staining and thin layer chromatography, adiponectin strongly upregulated lipid production in sebocytes. In three-dimensional culture of sebocytes, lipid synthesis was markedly enhanced in sebocytes treated with adiponectin. This study suggested that adiponectin plays a significant role in human sebaceous gland biology. Adiponectin signaling is a promising target in the clinical management of barrier disorders in which sebum production is decreased, such as in atopic dermatitis and aged skin. PMID:28081218

  19. Annexin A6 regulates adipocyte lipid storage and adiponectin release.

    PubMed

    Krautbauer, Sabrina; Haberl, Elisabeth M; Eisinger, Kristina; Pohl, Rebekka; Rein-Fischboeck, Lisa; Rentero, Carles; Alvarez-Guaita, Anna; Enrich, Carlos; Grewal, Thomas; Buechler, Christa; Neumeier, Markus

    2017-01-05

    Lipid storage and adipokine secretion are critical features of adipocytes. Annexin A6 (AnxA6) is a lipid-binding protein regulating secretory pathways and its role in adiponectin release was examined. The siRNA-mediated AnxA6 knock-down in 3T3-L1 preadipocytes impaired proliferation, and differentiation of AnxA6-depleted cells to mature adipocytes was associated with higher soluble adiponectin and increased triglyceride storage. The latter was partly attributed to reduced lipolysis. Accordingly, AnxA6 overexpression in 3T3-L1 adipocytes lowered cellular triglycerides and adiponectin secretion. Indeed, serum adiponectin was increased in AnxA6 deficient mice. Expression analysis identified AnxA6 protein to be more abundant in intra-abdominal compared to subcutaneous adipose tissues of mice and men. AnxA6 protein levels increased in white adipose tissues of obese mice and here, levels were highest in subcutaneous fat. AnxA6 protein in adipocytes was upregulated by oxidative stress which might trigger AnxA6 induction in adipose tissues and contribute to impaired fat storage and adiponectin release.

  20. Adiponectin as an anti-inflammatory factor

    PubMed Central

    Ouchi, Noriyuki; Walsh, Kenneth

    2009-01-01

    Obesity is characterized by low-grade systemic inflammation. Adiponectin is an adipose tissue-derived hormone, which is downregulated in obesity. Adiponectin displays protective actions on the development of various obesity-linked diseases. Several clinical studies demonstrate the inverse relationship between plasma adiponectin levels and several inflammatory markers including C-reactive protein. Adiponectin attenuates inflammatory responses to multiple stimuli by modulating signaling pathways in a variety of cell types. The anti-inflammatory properties of adiponectin may be a major component of its beneficial effects on cardiovascular and metabolic disorders including atherosclerosis and insulin resistance. In this reviews, we focus on the role of adiponectin in regulation of inflammatory response and discuss its potential as an antiinflammatory marker. PMID:17343838

  1. Adiponectin and end-stage renal disease.

    PubMed

    Markaki, Anastasia; Psylinakis, Emmanuel; Spyridaki, Aspasia

    2016-07-01

    Adiponectin (ADPN) is an adipokine with significant anti-inflammatory, insulin-sensitizing and anti-atherogenic properties, which is generally associated with a beneficial cardiometabolic profile. Paradoxically, end-stage renal disease (ESRD) is characterized by markedly increased plasma ADPN levels and increased cardiovascular risk. In spite of the cardioprotective properties attributed to adiponectin, cardiovascular complications remain the main cause of mortality in the ESRD population. Furthermore, these patients have enhanced chronic inflammation, increased insulin resistance and persistent protein-energy wasting. Studies of the impact of ADPN on clinical outcomes among ESRD patients have so far yielded contradictory results. This review article summarizes the current knowledge on ADPN functions and explores the role of ADPN in ESRD patients, with specific focus on inflammation, insulin resistance, cardiovascular disease and wasting.

  2. Adiponectin Potentially Contributes to the Antidepressive Effects of Baduanjin Qigong Exercise in Women With Chronic Fatigue Syndrome-Like Illness.

    PubMed

    Chan, Jessie S M; Li, Ang; Ng, Siu-Man; Ho, Rainbow T H; Xu, Aimin; Yao, Tzy-Jyun; Wang, Xiao-Min; So, Kwok-Fai; Chan, Cecilia L W

    2017-03-13

    Our recent study demonstrates that adiponectin signaling plays a significant role in mediating physical exercise-exerted effects on hippocampal neurogenesis and antidepression in mice. Whether the findings can be translated to humans remains unknown. This study aimed to investigate the effects of Baduanjin Qigong exercise on adiponectin and to evaluate whether adiponectin is involved in the antidepressive effects of Qigong exercise on chronic fatigue syndrome (CFS)-like illness. This is a randomized, waitlist-controlled trial. One hundred eight female participants were randomly assigned to either Qigong exercise or waitlist groups. Sixteen 1.5-h Qigong lessons were conducted. Outcome measures were taken at three time points. Baseline adiponectin levels were negatively associated with body weight, body mass index, waist circumference, hip circumference, and waist/hip ratio in women with CFS-like illness. Compared with the waitlist control, Qigong exercise significantly reduced anxiety and depression symptoms and significantly raised plasma adiponectin levels (median = 0.8 vs. -0.1, p < 0.05). More interestingly, increases in adiponectin levels following Qigong exercise were associated with decreases in depression scores for the Qigong group (r = -0.38, p = 0.04). Moreover, adjusted linear regression analysis further identified Qigong exercise and change in adiponectin levels as the significant factors accounting for reduction of depression symptoms. Baduanjin Qigong significantly increased adiponectin levels in females with CFS-like illness. Decreases in depression symptoms were associated with increases in adiponectin levels following Qigong exercise, indicating that the potential contribution of adiponectin to Qigong exercise elicited antidepressive effects in human subjects.

  3. GLUCOMANNAN AND GLUCOMANNAN PLUS SPIRULINA-ENRICHED SQUID-SURIMI ADDED TO HIGH SATURATED DIET AFFECT GLYCEMIA, PLASMA AND ADIPOSE LEPTIN AND ADIPONECTIN LEVELS IN GROWING FA/FA RATS.

    PubMed

    Vázquez-Velasco, Miguel; González-Torres, Laura; Méndez, María Teresa; Bastida, Sara; Benedí, Juana; González-Muñoz, M José; Sánchez-Muniz, Francisco J

    2015-12-01

    Type 2 diabetes is a very prevalent chronic disease. Among dietary factors for its prevention and treatment, interest has grown in satiating fibre (konjac glucomannan) and spirulina. Our previous studies suggest that glucomannan itself and/or in conjunction to spirulina displayed hypolipemic and antioxidant effects when incorporated to squid surimi as functional ingredients. The present study aims to determine whether glucomannan- enriched or glucomannan plus spirulina-enriched squid-surimi improve plasma glucose and insulin levels in Zucker fa/fa rats fed a high saturated fat diet. Twenty four growing rats, divided into three groups, were given modified AIN-93M diets for seven weeks: 30% squid-surimi control diet (C), 30% glucomannan-enriched squid-surimi diet (G) and 30% glucomannan plus spirulina-enriched squid-surimi diet (GS). All rats became hyperglycemics and hyperinsulinemics, but G and GS diets induced significantly lower glucose levels (20%; p < 0.05) but did not modify insulinemia with respect to C diet. GS animals showed higher HOMA-D (p < 0.05) than C ones suggesting increased insulin availability. Plasma leptin and adiponectin decreased in G and GS vs. C group (p < 0.05). Adipose adiponectin increased significantly in G and GS vs. C rats (16-20 times, p < 0.01). Leptin in adipose tissue was higher in GS vs. G group (p < 0.05). In conclusion, both glucomannan-diets were able to reduce hyperglycemia and increase adipose tissue adiponectin levels in fa/fa rats, suggesting an anti-hypertrophic and insulin-sensitizing adipokine effect in this tissue. Spirulina inclusion increased insulin availability. Although results are promising, the utility of consuming glucomannan surimis as part of usual diets demands future studies.

  4. Adiponectin: a manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease?

    PubMed Central

    2014-01-01

    Adiponectin is the most abundant peptide secreted by adipocytes, being a key component in the interrelationship between adiposity, insulin resistance and inflammation. Central obesity accompanied by insulin resistance is a key factor in the development of metabolic syndrome (MS) and future macrovascular complications. Moreover, the remarkable correlation between coronary artery disease (CAD) and alterations in glucose metabolism has raised the likelihood that atherosclerosis and type 2 diabetes mellitus (T2DM) may share a common biological background. We summarize here the current knowledge about the influence of adiponectin on insulin sensitivity and endothelial function, discussing its forthcoming prospects and potential role as a therapeutic target for MS, T2DM, and cardiovascular disease. Adiponectin is present in the circulation as a dimer, trimer or protein complex of high molecular weight hexamers, >400 kDa. AdipoR1 and AdipoR2 are its major receptors in vivo mediating the metabolic actions. Adiponectin stimulates phosphorylation and AMP (adenosin mono phosphate) kinase activation, exerting direct effects on vascular endothelium, diminishing the inflammatory response to mechanical injury and enhancing endothelium protection in cases of apolipoprotein E deficiency. Hypoadiponectinemia is consistently associated with obesity, MS, atherosclerosis, CAD, T2DM. Lifestyle correction helps to favorably modify plasma adiponectin levels. Low adiponectinemia in obese patients is raised via continued weight loss programs in both diabetic and nondiabetic individuals and is also accompanied by reductions in pro-inflammatory factors. Diet modifications, like intake of fish, omega-3 supplementation, adherence to a Mediterranean dietary pattern and coffee consumption also increase adiponectin levels. Antidiabetic and cardiovascular pharmacological agents, like glitazones, glimepiride, angiotensin converting enzyme inhibitors and angiotensin receptor blockers are also able to

  5. The aporphine alkaloid boldine induces adiponectin expression and regulation in 3T3-L1 cells.

    PubMed

    Yu, Bangning; Cook, Carla; Santanam, Nalini

    2009-10-01

    Adiponectin is an adipokine secreted by differentiated adipocytes. Clinical studies suggest a negative correlation between oxidative stress and adiponectin levels in patients with metabolic syndrome or cardiovascular disease. Natural compounds that can prevent oxidative stress mediated inhibition of adiponectin may be potentially therapeutic. Boldine, an aporphine alkaloid abundant in the medicinal plant Peumus boldus, is a powerful antioxidant. The current study demonstrates the effects of boldine on the expression of adiponectin and its regulators, CCAAT/enhancer binding protein-alpha (C/EBPalpha) and peroxisome proliferator-activated receptor (PPAR)-gamma, in 3T3-L1 cells. Differentiated 3T3-L1 adipocytes were exposed to either hydrogen peroxide (H(2)O(2)) (100 microM) or tumor necrosis factor-alpha (TNFalpha) (1 ng/mL) for 24 hours in the presence or absence of increasing concentrations of boldine (5-100 microM). Quantitative polymerase chain reaction showed that both the oxidants decreased the mRNA levels of adiponectin, PPARgamma, and C/EBPalpha to half of the control levels. Boldine, at all concentrations, counteracted the inhibitory effect of H(2)O(2) or TNFalpha and increased the expression of adiponectin and its regulators. The effect of boldine on adiponectin expression was biphasic, with the lower concentrations (5-25 microM) having a larger inductive effect compared to higher concentrations (50-100 microM). Boldine treatment alone in the absence of H(2)O(2) or TNFalpha was also able to induce adiponectin at the inductive phase of adipogenesis. Peroxisome proliferator response element-luciferase promoter transactivity analysis showed that boldine interacts with the PPAR response element and could potentially modulate PPAR responsive genes. Our results indicate that boldine is able to modulate the expression of adiponectin and its regulators in 3T3-L1 cells and has the potential to be beneficial in obesity-related cardiovascular disease.

  6. The Aporphine Alkaloid Boldine Induces Adiponectin Expression and Regulation in 3T3-L1 Cells

    PubMed Central

    Yu, Bangning; Cook, Carla

    2009-01-01

    Abstract Adiponectin is an adipokine secreted by differentiated adipocytes. Clinical studies suggest a negative correlation between oxidative stress and adiponectin levels in patients with metabolic syndrome or cardiovascular disease. Natural compounds that can prevent oxidative stress mediated inhibition of adiponectin may be potentially therapeutic. Boldine, an aporphine alkaloid abundant in the medicinal plant Peumus boldus, is a powerful antioxidant. The current study demonstrates the effects of boldine on the expression of adiponectin and its regulators, CCAAT/enhancer binding protein-α (C/EBPα) and peroxisome proliferator-activated receptor (PPAR)-γ, in 3T3-L1 cells. Differentiated 3T3-L1 adipocytes were exposed to either hydrogen peroxide (H2O2) (100 μM) or tumor necrosis factor-α (TNFα) (1 ng/mL) for 24 hours in the presence or absence of increasing concentrations of boldine (5–100 μM). Quantitative polymerase chain reaction showed that both the oxidants decreased the mRNA levels of adiponectin, PPARγ, and C/EBPα to half of the control levels. Boldine, at all concentrations, counteracted the inhibitory effect of H2O2 or TNFα and increased the expression of adiponectin and its regulators. The effect of boldine on adiponectin expression was biphasic, with the lower concentrations (5–25 μM) having a larger inductive effect compared to higher concentrations (50–100 μM). Boldine treatment alone in the absence of H2O2 or TNFα was also able to induce adiponectin at the inductive phase of adipogenesis. Peroxisome proliferator response element-luciferase promoter transactivity analysis showed that boldine interacts with the PPAR response element and could potentially modulate PPAR responsive genes. Our results indicate that boldine is able to modulate the expression of adiponectin and its regulators in 3T3-L1 cells and has the potential to be beneficial in obesity-related cardiovascular disease. PMID:19857072

  7. Prediagnostic Plasma Adiponectin and Survival among Patients with Colorectal Cancer.

    PubMed

    Chong, Dawn Q; Mehta, Raaj S; Song, Mingyang; Kedrin, Dmitriy; Meyerhardt, Jeffrey A; Ng, Kimmie; Wu, Kana; Fuchs, Charles S; Giovannucci, Edward L; Ogino, Shuji; Chan, Andrew T

    2015-12-01

    Circulating adiponectin is inversely related to the risk of colorectal cancer. However, its influence on colorectal cancer survival is unclear. We conducted a prospective study to evaluate the association between prediagnostic plasma levels of adiponectin and mortality in patients with colorectal cancer. We identified 621 incident colorectal cancer cases who provided blood specimens prior to diagnosis within the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (CI). After a median follow-up of 9 years, there were 269 (43%) total deaths, of which 181 (67%) were due to colorectal cancer. Compared with participants in the lowest quartile of adiponectin, those in the highest quartile had multivariate HRs of 1.89 (95% CI, 1.21-2.97; P(trend) = 0.01) for colorectal cancer-specific mortality and 1.66 (95% CI, 1.15-2.39; P(trend) = 0.009) for overall mortality. The apparent increased risk in colorectal cancer-specific mortality was more pronounced in patients with metastatic disease (HR, 3.02: 95% CI, 1.50-6.08). Among patients with colorectal cancer, prediagnostic plasma adiponectin is associated with an increased risk of colorectal cancer-specific and overall mortality and is more apparent in patients with metastatic disease. Adiponectin may be a marker for cancers which develop through specific pathways that may be associated with worsened prognosis. Further studies are needed to validate these findings.

  8. Prediagnostic Plasma Adiponectin and Survival among Patients with Colorectal Cancer

    PubMed Central

    Chong, Dawn Q.; Mehta, Raaj S.; Song, Mingyang; Kedrin, Dmitriy; Meyerhardt, Jeffrey A.; Ng, Kimmie; Wu, Kana; Fuchs, Charles S.; Giovannucci, Edward L.; Ogino, Shuji; Chan, Andrew T.

    2015-01-01

    Circulating adiponectin is inversely related to the risk of colorectal cancer (CRC). However, its influence on CRC survival is unclear. We conducted a prospective study to evaluate the association between prediagnostic plasma levels of adiponectin and mortality in patients with CRC. We identified 621 incident CRC cases who provided blood specimens prior to diagnosis within the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). After a median follow-up of 9 years, there were 269 (43%) total deaths, of which 181 (67%) were due to CRC. Compared with participants in the lowest quartile of adiponectin, those in the highest quartile had multivariate HRs of 1.89 (95% CI, 1.21–2.97; Ptrend = 0.01) for CRC-specific mortality and 1.66 (95% CI, 1.15–2.39; Ptrend = 0.009) for overall mortality. The apparent increased risk in CRC-specific mortality was more pronounced in patients with metastatic disease (HR 3.02, 95% CI, 1.50–6.08). Among patients with CRC, prediagnostic plasma adiponectin is associated with an increased risk of CRC-specific and overall mortality, and is more apparent in patients with metastatic disease. Adiponectin may be a marker for cancers which develop through specific pathways that may be associated with worsened prognosis. Further studies are needed to validate these findings. PMID:26382604

  9. Beneficial effects of adiponectin on periodontal ligament cells under normal and regenerative conditions.

    PubMed

    Nokhbehsaim, Marjan; Keser, Sema; Nogueira, Andressa Vilas Boas; Cirelli, Joni Augusto; Jepsen, Søren; Jäger, Andreas; Eick, Sigrun; Deschner, James

    2014-01-01

    Type 2 diabetes and obesity are increasing worldwide and linked to periodontitis, a chronic disease which is characterized by the irreversible destruction of the tooth-supporting tissues, that is, periodontium. The mechanisms underlying the association of diabetes mellitus and obesity with periodontal destruction and compromised periodontal healing are not well understood, but decreased plasma levels of adiponectin, as found in diabetic and obese individuals, might be a critical mechanistic link. The aim of this in vitro study was to examine the effects of adiponectin on periodontal ligament (PDL) cells under normal and regenerative conditions, and to study the regulation of adiponectin and its receptors in these cells. Adiponectin stimulated significantly the expression of growth factors and extracellular matrix, proliferation, and in vitro wound healing, reduced significantly the constitutive tumor necrosis factor-α expression, and caused a significant upregulation of its own expression. The beneficial actions of enamel matrix derivative on a number of PDL cell functions critical for periodontal regeneration were partially enhanced by adiponectin. The periodontopathogen Porphyromonas gingivalis inhibited the adiponectin expression and stimulated the expression of its receptors. In conclusion, reduced levels of adiponectin, as found in type 2 diabetes and obesity, may compromise periodontal health and healing.

  10. 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

    2017-02-11

    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 NaAsO2) 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.

  11. The effects of vitamin D supplementation on adiponectin level and insulin resistance in first-degree relatives of subjects with type 2 diabetes: a randomized double-blinded controlled trial

    PubMed Central

    Mohammadi, Seyed Mohammad; Eghbali, Seyed Ahmad; Soheilikhah, Sedighah; Ashkezari, Saeedeh Jam; Salami, Maryam; Afkhami-Ardekani, Mohammad; Afkhami-Ardekani, Arezoo

    2016-01-01

    Background Despite the certain role of both vitamin D and adiponectin in the regulation of insulin sensitivity, the interaction between these two agents has remained uncertain. Objective The present study aimed to determine whether vitamin D is able to change plasma adiponectin and affect glucose homeostasis and insulin sensitivity in first-degree relatives of subjects with type 2 diabetes. Methods This randomized clinical trial was conducted at Clinic of Shahid Sadoughi Hospital in Yazd, Iran, from January 25, 2012 to December 25, 2014. In this randomized, double-blinded controlled trial, 64 first-degree relatives of type 2 diabetic patients were assigned randomly to receive either vitamin D supplement (50000 IU vitamin D tablet weekly) plus lifestyle change as the intervention group (n = 32) or placebo plus lifestyle change as the control group (n = 32) for twelve weeks (three months). Results Fifty-three patients (28 in the intervention group and 25 in the control group) completed the study. Serum levels of vitamin D increased while insulin level and consequently insulin resistance (calculated by HOMA formula) significantly decreased in the case group (p-value <0.001 for all variables). Although the values of these three biomarkers showed a slight increase in control group, the changes were not statistically significant. The levels of the changes in other markers including adiponectin, Fasting Blood Sugar (FBS), triglyceride, and total cholesterol remained insignificant in both study groups after completing interventions compared with before interventions. Conclusion This study showed that decreased insulin resistance is expected by administrating vitamin D supplement in first-degree relatives of the patients with diabetes mellitus. Trial Registration The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: 201105176430N1. Funding The authors received no financial support for the research or publication of this

  12. Adiponectin Deficiency Leads to Female Subfertility and Ovarian Dysfunctions in Mice.

    PubMed

    Cheng, Lixian; Shi, Hui; Jin, Yan; Li, Xiaoxi; Pan, Jinshun; Lai, Yimei; Lin, Yan; Jin, Ya; Roy, Gaurab; Zhao, Allan; Li, Fanghong

    2016-12-01

    Adipose tissue plays an important role in regulating female fertility, owing to not only its energy stores but also the endocrine actions of secreted adipokines. As one of the adipokines, adiponectin is almost exclusively secreted from the fat, and its circulating concentration is paradoxically reduced in obesity. Although recent studies implied a purported positive role of adiponectin in ovarian functions, definitive in vivo evidence has been sorely lacking. We have consistently observed subfertility in female adiponectin null mice and therefore postulated a protective role of adiponectin in ovarian functions. Female adiponectin null mice displayed impaired fertility, reduced retrieval of oocytes, disrupted estrous cycle, elevated number of atretic follicles, and impaired late folliculogenesis. Analysis of their sera revealed a significant decrease in estradiol and FSH but an increase in LH and testosterone at proestrus. In addition, we found marked reduction of progesterone levels at diestrus, a significant decrease in LH receptor expression as well as in the number of GnRH immunoreactive neurons. Adiponectin deficiency also altered the peak concentrations of LH surge and led to lower expression of Cytochrome P450 family 11 subfamily A member 1 (P450scc), an enzyme critical for progesterone synthesis, as well as an increase in BCL2 associated X, apoptosis regulator and Insulin like growth factor binding protein 4 in atretic follicles. These physiological and molecular events were independent of insulin sensitivity. Thus, we have revealed a novel mechanism linking adiponectin and female fertility that entails regulation of reproductive hormone balance and ovarian follicle development.

  13. Alleviation of insulin resistance and liver damage by oral administration of Imm124-E is mediated by increased Tregs and associated with increased serum GLP-1 and adiponectin: results of a phase I/II clinical trial in NASH

    PubMed Central

    Mizrahi, Meir; Shabat, Yehudit; Ben Ya’acov, Ami; Lalazar, Gadi; Adar, Tomer; Wong, Victor; Muller, Brian; Rawlin, Grant; Ilan, Yaron

    2012-01-01

    Background Nonalcoholic steatohepatitis (NASH) is considered to be part of the nonalcoholic fatty liver disorders and its incidence is increasing. Imm124-E (Immuron Ltd, Melbourne, Australia), containing hyperimmune bovine colostrum, has been shown to exert an immunomodulatory effect and to alleviate target organ damage in animal models of NASH. The aim of our study was to determine the safety and efficacy of oral administration of Imm124-E to patients with insulin resistance and NASH. Methods In an open-label trial, ten patients with biopsy-proven NASH and insulin resistance were orally treated with Imm124-E for 30 days. Results Oral administration of Imm124-E was safe, and no side effects were noted. Alleviation of insulin resistance was reflected by significantly improved hemoglobin A1c (HbA1c) values in all ten treated patients. For between five and eight responders, the following effects were noted: a decrease in fasting glucose levels; improved oral glucose tolerance test (OGGT) and homeostatic model assessment insulin resistance (HOMA) scores; and alleviation in lipid profile. These effects were accompanied by increased serum levels of glucagon-like peptide 1 (GLP-1), adiponectin and T regulatory cells. Conclusion Hyperimmune colostrum alleviates NASH. PMID:23293533

  14. Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels.

    PubMed

    Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B; Dong, Xiao; Wang, Hongjun

    2015-05-28

    Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice.

  15. Effect of Extended-Release Niacin/Laropiprant Combination on Plasma Adiponectin and Insulin Resistance in Chinese Patients with Dyslipidaemia

    PubMed Central

    Yang, Ya-Ling; Masuda, Daisaku; Yamashita, Shizuya; Tomlinson, Brian

    2015-01-01

    Objectives. This study examined whether the increase of adiponectin associated with extended-release (ER) niacin/laropiprant combination attenuates the adverse effect of niacin on glucose and insulin resistance in Hong Kong Chinese patients with dyslipidaemia. Methods. Patients (N = 121) were treated with ER niacin/laropiprant 1 g/20 mg for 4 weeks and then the dose was doubled for an additional 8 weeks. Measurements of fasting lipids, glucose, insulin, and adiponectin were performed at baseline and during the study. Results. There were significant (P < 0.001) increases in glucose (9.4 ± 13.1%), insulin (70.2 ± 91.0%), HOMA-IR (87.8 ± 103.9%), and adiponectin (169.3 ± 111.6%). The increase in adiponectin was significantly associated with increase in glucose (r = 0.221, P < 0.05), insulin (r = 0.184, P < 0.05), and HOMA-IR (r = 0.237, P < 0.01) and the association remained significant after adjustment for changes in body weight or body fat mass. Conclusion. Treatment with ER niacin/laropiprant led to a significant increase in adiponectin levels but worsening of glucose levels and insulin resistance, and the increase in adiponectin and insulin resistance were correlated suggesting the increase in adiponectin did not ameliorate the deterioration in insulin resistance. Clinical trial is registered with number on WHO-ICTRP: ChiCTR-ONC-10001038. PMID:26063948

  16. Adiponectin regulate growth hormone secretion via adiponectin receptor mediated Ca(2+) signalling in rat somatotrophs in vitro.

    PubMed

    Steyn, F J; Boehme, F; Vargas, E; Wang, K; Parkington, H C; Rao, J R; Chen, C

    2009-08-01

    Obesity is associated with reduced levels of growth hormone (GH) and the disruption of pulsatile GH secretion. This results in relative GH deficiency. It is likely that a regulatory relationship between GH secretion and adipose tissue exists as the secretion of GH recovers to normal levels after a reduction in body weight. This report characterise the expression and interaction of adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) and adiponectin, respectively, in regulating the activity of GH secreting cells. Polymerase chain reaction analysis of the GH3 cell line, rat anterior pituitary gland and isolated somatotroph cells from transgenic GFP expressing mice confirmed the expression of both AdipoR1 and AdipoR2 in GH secretory cells. Because GH cells expressed both receptors, it is likely that the measured increase in GH secretion, observed in primary cultured rat pituitary cells after 30 min of incubation with full-length murine adiponectin, was mediated by a direct receptor regulated process. Adiponectin induced an increase in intracellular Ca(2+) through both the influx of extracellular Ca(2+) and the release of intracellular Ca(2+) stores resulting in the secretion of GH. Furthermore, results confirm that this increase in GH secretion depended mainly on an increase in Ca(2+) influx through L-type Ca(2+) channels. It is concluded that adiponectin directly regulates GH secretion from somatotrophs by binding to either adiponectin receptor, and that this is mediated via a similar process observed after the stimulation of GH secretion by GH-releasing hormone.

  17. Melatonin modulates adiponectin expression on murine colitis with sleep deprivation

    PubMed Central

    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

    2016-01-01

    AIM To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation. METHODS 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. RESULTS 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. CONCLUSION 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. PMID:27672276

  18. Adiponectin: an attractive marker for metabolic disorders in Chronic Obstructive Pulmonary Disease (COPD).

    PubMed

    Bianco, Andrea; Mazzarella, Gennaro; Turchiarelli, Viviana; Nigro, Ersilia; Corbi, Graziamaria; Scudiero, Olga; Sofia, Matteo; Daniele, Aurora

    2013-10-14

    Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung disease which may be complicated by development of co-morbidities including metabolic disorders. Metabolic disorders commonly associated with this disease contribute to lung function impairment and mortality. Systemic inflammation appears to be a major factor linking COPD to metabolic alterations. Adipose tissue seems to interfere with systemic inflammation in COPD patients by producing a large number of proteins, known as "adipokines", involved in various processes such as metabolism, immunity and inflammation. There is evidence that adiponectin is an important modulator of inflammatory processes implicated in airway pathophysiology. Increased serum levels of adiponectin and expression of its receptors on lung tissues of COPD patients have recently highlighted the importance of the adiponectin pathway in this disease. Further, in vitro studies have demonstrated an anti-inflammatory activity for this adipokine at the level of lung epithelium. This review focuses on mechanisms by which adiponectin is implicated in linking COPD with metabolic disorders.

  19. Study of the correlation between growth hormone deficiency and serum leptin, adiponectin, and visfatin levels in adults.

    PubMed

    Li, Z-P; Zhang, M; Gao, J; Zhou, G-Y; Li, S-Q; An, Z-M

    2014-02-14

    We aimed to determine the significance and changes in leptin, adiponectin (ADP), and visfatin levels in adults with growth hormone deficiency (GHD). Forty adults (19 men, 21 women) who had been diagnosed with GHD comprised the observation group, while 36 healthy adults (18 men, 18 women) were used as the control group. Fasting venous blood was collected to detect leptin, ADP, and visfatin levels. There was no statistically significant difference (P > 0.05) between the GHD group and the control group in terms of gender ratio, age, and body mass index. The waist-to-hip ratio (0.894 ± 0.061 vs 0.830 ± 0.481), cholesterol (4.99 ± 1.046 vs 4.18 ± 0.683), triglyceride (1.97 ± 1.428 vs 1.08 ± 0.403), LDL (2.91 ± 0.980 vs 2.29 ± 0.540), leptin (3.00 ± 1.233 vs 1.89 ± 1.554), ADP (15.26 ± 6.449 vs 10.24 ± 7.608), and visfatin levels (10.42 ± 3.715 vs 5.87 ± 3.90) in the GHD group were significantly higher than those in the control group (all P < 0.05). The levels of growth hormone (1.68 ± 1.67 vs 15.53 ± 6.23), insulin-like growth factor-1 (IGF-1, 22.64 ± 16.41 vs 61.85 ± 28.48), IGF-binding protein-3 (4889 ± 2962 vs 6866 ± 3823), and dehydroepiandrosterone sulfate (1.466 ± 1.804 vs 6.000 ± 2.767) in the GHD group were significantly lower than those in the control group (all P < 0.05). Correlation analysis demonstrated that leptin level was positively correlated to ADP and visfatin in both the GHD and control groups and negatively correlated to IGF-1 (r = 0.332, P < 0.05). Logistic regression analysis demonstrated that leptin, ADP, and visfatin were independent risk factors for adults with GHD.

  20. Low-molecular-weight adiponectin is more closely associated with disease activity of rheumatoid arthritis than other adiponectin multimeric forms.

    PubMed

    Li, Ping; Yang, Li; Ma, Cui-Li; Liu, Bo; Zhang, Xin; Ding, Rui; Bi, Li-qi

    2015-06-01

    Adiponectin is divided into high-molecular-weight (HMW), medium-molecular-weight (MMW), and low-molecular-weight (LMW) forms. These forms differ not only in the number of adiponectin molecules but also in their biological activity. There are conflicting findings regarding the role of adiponectin in rheumatoid arthritis (RA). Moreover, few reports have described the relationships between serum adiponectin multimers levels and RA. Therefore, we examined the association of total adiponectin and its multimers with RA. Two study groups were examined: 180 recently diagnosed untreated RA patients with disease duration less than 1 year (RA group) and 160 age- and sex-matched control subjects (control group). RA-related factors, blood pressure, body mass index, glucose, complete lipid profile, and adiponectin multimers were measured. The levels of total adiponectin and each multimer of adiponectin were significantly lower in the RA than in the control (P < 0.01). Serum levels of total, HMW, MMW, and LMW were positively correlated with triglycerides levels and negatively correlated with the Disease Activity Score for 28 joints (DAS28). Multivariate regression analysis showed that total, HMW, and MMW adiponectin were independently associated with serum triglycerides level. LMW adiponectin was independently correlated with serum triglycerides level and DAS28. The decreased LMW adiponectin levels may be associated with disease activity of RA.

  1. Association of Plasma Adiponectin and Oxidized Low-Density Lipoprotein with Carotid Intima-Media Thickness in Diabetic Nephropathy

    PubMed Central

    Georgoulidou, Anastasia; Roumeliotis, Athanasios; Roumeliotis, Stefanos; Giannakopoulou, Efstathia; Papanas, Nikolaos; Passadakis, Ploumis; Manolopoulos, Vangelis G.; Vargemezis, Vassilis

    2015-01-01

    Aims. We sought to determine the association between levels of adiponectin and oxidized low-density lipoprotein (ox-LDL) in patients with diabetic nephropathy as well as their effect on carotid intima-media thickness (cIMT). Methods. Adiponectin and ox-LDL were determined in 25 diabetic patients without nephropathy and 94 patients at different stages of diabetic nephropathy including subjects on hemodialysis. cIMT was measured using real-time B-mode ultrasonography. Results. Plasma adiponectin levels increased significantly with severity of diabetic nephropathy (P = 0.002), on the contrary to ox-LDL which decreased with disease severity (P < 0.001). cIMT was significantly higher at late stages of diabetic nephropathy compared with early stages (P = 0.022). Adiponectin was a significant negative predictor of ox-LDL levels (β = −5.45, P = 0.023), independently of confounding factors. There was no significant correlation between cIMT and adiponectin or ox-LDL either in the total sample population or according to disease staging. Cluster analysis showed that patients with the highest cIMT values, highest levels of adiponectin, and lowest levels of ox-LDL were included in one cluster and all assigned to stage 5 of diabetic nephropathy. Conclusions. There was no significant association between adiponectin or ox-LDL and cIMT and, therefore, other factors affecting this surrogate marker of cardiovascular disease in diabetic nephropathy should be sought. PMID:26064982

  2. 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.

  3. Peroxisome proliferator-activated receptor γ enhances adiponectin secretion via up-regulating DsbA-L expression.

    PubMed

    Jin, Dan; Sun, Jun; Huang, Jing; Yu, Xiaoling; Yu, An; He, Yiduo; Li, Qiang; Yang, Zaiqing

    2015-08-15

    Disulfide-bond A oxidoreductase like-protein (DsbA-L) was identified as a molecular chaperone facilitating the assembly and secretion of adiponectin, an adipokine with multiple beneficial effects. In obesity the level of DsbA-L is reduced with a concomitant decrease of the circulating adiponectin level, especially of the high molecular weight form (HMW). Both rodent and human studies have shown that the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-γ agonists increase adiponectin levels in serum by activating PPARγ, which up-regulates critical endoplasmic reticulum (ER) chaperones thus facilitating protein folding. As shown in the present study, overexpression of PPARγ in human embryonic kidney (HEK) 293 cells elicited the cellular release of HMW adiponectin. PPARγ enhanced expression of DsbA-L by binding directly to peroxisome proliferator response element (PPRE) site within the DsbA-L promoter. Conversely, in differentiated 3T3-L1 cells, PPARγ knockdown resulted in decreased expression of Adiponectin, DsbA-L and ERp44. DsbA-L expression increased after PPARγ agonist treatment and decreased upon treatment with PPARγ antagonist in 3T3-L1 adipocytes. DsbA-L deficiency in differentiated 3T3-L1 cells impaired the secretion of adiponectin. We therefore propose that DsbA-L plays an important role in facilitating HMW adiponectin formation and release from cells under the regulation of PPARγ.

  4. 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

  5. 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

  6. Evaluation of Serum Adiponectin Concentrations Among Drug Abusers on Methadone Maintenance Treatment

    PubMed Central

    Montazerifar, Farzaneh; Karajibani, Mansour; Lashkaripour, Kobra; Yousefi, Maryam

    2013-01-01

    Background: Adiponectin, an adipocyte-derived protein, modulates a number of metabolic processes. Methadone maintenance treatment (MMT) changes the level of hormones produced by adipose tissue in addicts. However, current data remains contradictory. Objectives: The aim of this study was to evaluate the effect of MMT on serum adiponectin levels in drug addicts. Materials and Methods: Twenty-five drug abusers with a mean age of 37.4 ± 8.7 years were referred to the Baharan Hospital, Zahedan, and 22 healthy age-matched control subjects with a mean age of 35 ± 9.5 years were enrolled in the study. Addicts were treated with methadone at (40 to 120 mg/d) for six months. Measurement of anthropometric parameters, serum adiponectin, and biochemical parameter levels, were assessed in the addicts, before and after six months of MMT, but only once in the healthy controls. Results: The mean basal serum adiponectin level was not significantly lower in the drug abuser group compared to the healthy subjects (P > 0.05). After six months of MMT, the mean serum adiponectin level of the drug addicts was not significantly different from their mean baseline level or that of the healthy subjects (P > 0.05). However, the mean baseline serum adiponectin level was significantly lower in overweight/obese addicts when compared to underweight patients and healthy individuals (P < 0.001). After six months of MMT, the mean level of serum adiponectin increased significantly in the underweight subjects compared to the normal weight and overweight/obese subjects (P < 0.0001) and the control group (P < 0.001). Adiponectin concentration was correlated inversely with body mass index and positively correlated with waist circumference and serum high-density lipoprotein levels. Conclusions: This study showed that MMT did not markedly alter the concentration of serum adiponectin in drug abusers. However, in regard to the variations in the serum lipid profiles and anthropometric parameters, the findings

  7. A low-glycemic load diet reduces serum C-reactive protein and modestly increases adiponectin in overweight and obese adults.

    PubMed

    Neuhouser, Marian L; Schwarz, Yvonne; Wang, Chiachi; Breymeyer, Kara; Coronado, Gloria; Wang, Chin-Yun; Noar, Karen; Song, Xiaoling; Lampe, Johanna W

    2012-02-01

    Low-glycemic load (GL) diets improve insulin resistance and glucose homeostasis in individuals with diabetes. Less is known about whether low-GL diets, independent of weight loss, improve the health profile for persons without diabetes or other preexisting conditions. We conducted a randomized, cross-over feeding study testing low- compared to High-GL diets on biomarkers of inflammation and adiposity in healthy adults. Eighty participants (n = 40 with BMI 18.5-24.9 kg/m²; n = 40 with BMI 28.0-40.0 kg/m²) completed two 28-d feeding periods in random order where one period was a high-GL diet (mean GL/d = 250) and the other a low-GL diet (mean GL/d = 125). Diets were isocaloric with identical macronutrient content (as percent energy). All food was provided and participants maintained weight and usual physical activity. Height, weight, and DXA were measured at study entry and weight assessed again thrice per week. Blood was drawn from fasting participants at the beginning and end of each feeding period and serum concentrations of high-sensitivity CRP, serum amyloid A, IL-6, leptin, and adiponectin were measured. Linear mixed models tested the intervention effect on the biomarkers; models were adjusted for baseline biomarker concentrations, diet sequence, feeding period, age, sex, and body fat mass. Among participants with high-body fat mass (>32.0% for males and >25.0% for females), the low-GL diet reduced CRP (P = 0.02) and marginally increased adiponectin (P = 0.06). In conclusion, carbohydrate quality, independent of energy, is important. Dietary patterns emphasizing low-GL foods may improve the inflammatory and adipokine profiles of overweight and obese individuals.

  8. The Relationship between Maternal Plasma Leptin and Adiponectin Concentrations and Newborn Adiposity

    PubMed Central

    Castro, Natália P.; Euclydes, Verônica V.; Simões, Fernanda A.; Vaz-de-Lima, Lourdes R. A.; De Brito, Cyro A.; Luzia, Liania A.; Devakumar, Delan; Rondó, Patrícia H. C.

    2017-01-01

    Increased maternal blood concentrations of leptin and decreased adiponectin levels, which are common disturbances in obesity, may be involved in offspring adiposity by programming fetal adipose tissue development. The aim of this study was to assess the relationship between maternal leptin and adiponectin concentrations and newborn adiposity. This was a cross-sectional study involving 210 healthy mother-newborn pairs from a public maternity hospital in São Paulo, Brazil. Maternal blood samples were collected after delivery and leptin and adiponectin concentrations were measured by enzyme-linked immunosorbent assay. Newborn body composition was estimated by air displacement plethysmography. The association between maternal leptin and adiponectin concentrations and newborn adiposity (fat mass percentage, FM%) was evaluated by multiple linear regression, controlling for maternal age, socioeconomic status, parity, pre-pregnancy body mass index (BMI), weight gain, gestational age, and newborn age at the time of measurement. No relationship was found between maternal leptin and FM% of male or female newborn infants. Maternal adiponectin (p = 0.001) and pre-pregnancy BMI (p < 0.001; adj. R2 = 0.19) were positively associated with FM% of newborn males, indicating that maternal adiponectin is involved in fetal fat deposition in a sex-specific manner. Large-scale epidemiological, longitudinal studies are necessary to confirm our results. PMID:28241462

  9. Adiponectin, leptin and IL-1 β in elderly diabetic patients with mild cognitive impairment.

    PubMed

    Gorska-Ciebiada, Malgorzata; Saryusz-Wolska, Malgorzata; Borkowska, Anna; Ciebiada, Maciej; Loba, Jerzy

    2016-04-01

    The aim of the study was to determine the serum levels of adiponectin, leptin and IL-1 β in elderly diabetic patients with and without mild cognitive impairment (MCI) and to examine the associations of these markers with clinical and cognitive parameters. A biochemical evaluation was performed of 62 seniors with type 2 diabetes (T2DM) and MCI, and 132 seniors with T2DM but without MCI (controls). Serum leptin and IL-1 β levels were higher and adiponectin concentration was lower in MCI patients than controls. In MCI subjects, adiponectin level was negatively correlated with leptin, IL-1 β levels and BMI. Leptin concentration was correlated with IL-1 β level. Univariate logistic regression models revealed that the factors which increased the likelihood of diagnosis of MCI in elderly patients with T2DM were higher levels of HbA1c, leptin, IL-1 β and triglycerides, as well as lower levels of adiponectin and HDL cholesterol. Similarly, previous CVD, hypertension, hyperlipidemia, retinopathy, nephropathy, hypoglycemia, longer duration of diabetes, increased number of co-morbidities, older age, fewer years of formal education were found to be associated with MCI. The multivariable model indicated fewer years of formal education, previous CVD, hypertension, increased number of co-morbidities, higher HbA1c and IL-1 β levels and lower adiponectin level. Elderly diabetic patients with MCI have higher levels of leptin and IL-1 β and lower levels of adiponectin. Further prospective studies are needed to determine the role of these markers in the progression to dementia.

  10. Adiponectin, C-reactive protein, fibrinogen and tissue plasminogen activator antigen levels among glucose-intolerant women with and without histories of gestational diabetes

    PubMed Central

    Kim, C.; Christophi, C. A.; Goldberg, R. B.; Perreault, L.; Dabelea, D.; Marcovina, S. M.; Pi-Sunyer, X.; Barrett-Connor, E.

    2015-01-01

    Aim To examine concentrations of biomarkers (adiponectin, C-reactive protein, fibrinogen and tissue plasminogen-activator antigen) associated with glucose homeostasis and diabetes risk by history of gestational diabetes. Methods We conducted a secondary analysis of the Diabetes Prevention Program, a randomized trial of lifestyle intervention or metformin for diabetes prevention. At baseline, participants were overweight and had impaired glucose tolerance. Biomarkers at baseline and 1 year after enrolment were compared between parous women with (n=350) and without a history of gestational diabetes (n=1466). Cox proportional hazard models evaluated whether history of gestational diabetes was associated with diabetes risk, after adjustment for baseline biomarker levels as well as for change in biomarker levels, demographic factors and anthropometrics. Results At baseline, women with histories of gestational diabetes had lower adiponectin (7.5 μg/ml vs. 8.7 μg/ml; p<0.0001) and greater log C-reactive protein (−0.90 mg/l vs. −0.78 mg/l, p=0.04) levels than women without histories of gestational diabetes, but these associations did not persist after adjustment for demographic factors. Fibrinogen and tissue plasminogen-activator antigen were similar between women with and without histories of gestational diabetes. Women with and without histories of gestational diabetes had a similar pattern of changes in biomarkers within randomization arm. Adjustment for age, race/ethnicity, baseline weight, change in weight, baseline biomarker level and change in biomarker level did not significantly alter the association between history of gestational diabetes and diabetes risk. Conclusions Among women with impaired glucose tolerance, biomarkers in women with and without histories of gestational diabetes are similar and respond similarly to lifestyle changes and metformin. Adjustment for biomarker levels did not explain the higher risk of diabetes observed in women with

  11. Plasma adiponectin in nonalcoholic fatty liver is related to hepatic insulin resistance and hepatic fat content, not to liver disease severity.

    PubMed

    Bugianesi, Elisabetta; Pagotto, Uberto; Manini, Rita; Vanni, Ester; Gastaldelli, Amalia; de Iasio, Rosaria; Gentilcore, Elena; Natale, Stefania; Cassader, Maurizio; Rizzetto, Mario; Pasquali, Renato; Marchesini, Giulio

    2005-06-01

    Plasma levels of adiponectin are decreased in patients with nonalcoholic fatty liver disease (NAFLD), but the relationship among plasma adiponectin, insulin sensitivity, and histological features is unclear. In 174 NAFLD patients and 42 controls, we examined plasma adiponectin concentrations in relation to 1) lipid profile, indices of insulin resistance, and features of the metabolic syndrome (n = 174); 2) hepatic insulin resistance (clamp technique with tracer infusion) (10 patients); and 3) histological features at liver biopsy (n = 116). When the data from all subjects were combined, plasma adiponectin levels were positively associated with increased age, female gender, and plasma high-density lipoprotein levels, and negatively associated with waist circumference, body mass index, triglycerides, indices of insulin resistance, and aminotransferase levels, and also predicted the presence of the metabolic syndrome. In step-wise regression, increased age, female gender, waist circumference, triglyceride levels, and homeostasis model assessment independently associated with adiponectin (adjusted R(2), 0.329). In NAFLD, adiponectin was only associated with increased age, female gender, and triglycerides (adjusted R(2), 0.245). When the measured histological parameters were included in the model, plasma adiponectin levels were also inversely proportional to the percentage of hepatic fat content (adjusted R(2), 0.221), whereas necroinflammation and fibrosis did not fit in the model. Adiponectin was negatively correlated with insulin-suppressed endogenous glucose production during the clamp (P = 0.011). The results demonstrate that decreased levels of circulating adiponectin in NAFLD are related to hepatic insulin sensitivity and to the amount of hepatic fat content. Hypoadiponectinemia in NAFLD is part of a metabolic disturbance characterized by ectopic fat accumulation in the central compartment.

  12. Adiponectin enhances bone marrow mesenchymal stem cell resistance to flow shear stress through AMP-activated protein kinase signaling

    PubMed Central

    Zhao, Lin; Fan, Chongxi; Zhang, Yu; Yang, Yang; Wang, Dongjin; Deng, Chao; Hu, Wei; Ma, Zhiqiang; Jiang, Shuai; Di, Shouyi; Qin, Zhigang; Lv, Jianjun; Sun, Yang; Yi, Wei

    2016-01-01

    Adiponectin has been demonstrated to protect the cardiovascular system and bone marrow mesenchymal stem cells (BMSCs). However, it is unclear whether adiponectin can protect BMSCs against flow shear stress (FSS). In this study, our aim was to explore the effects of adiponectin on BMSCs and to explore the role of AMP-activated protein kinase (AMPK) signaling in this process. Shear stress significantly inhibits the survival and increases the apoptosis of BMSCs in an intensity-dependent manner. The expression levels of TGF-β, bFGF, VEGF, PDGF, and Bcl2 are simultaneously reduced, and the phosphorylation levels of AMPK and ACC, as well as the expression level of Bax, are increased. Supplementation with adiponectin promotes the survival of BMSCs; reverses the changes in the expression levels of TGF-β, bFGF, VEGF, PDGF, Bcl2, and Bax; and further amplifies the phosphorylation of AMPK and ACC. Furthermore, the protective effects of adiponectin can be partially neutralized by AMPK siRNA. In summary, we have demonstrated for the first time that adiponectin can effectively protect BMSCs from FSS and that this effect depends, at least in part, on the activation of AMPK signaling. PMID:27418435

  13. ADIPONECTIN IN SEVERE PREECLAMPSIA

    PubMed Central

    Nien, Jyh Kae; Mazaki-Tovi, Shali; Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Gotsch, Francesca; Pineles, Beth L.; Gomez, Ricardo; Edwin, Samuel; Mazor, Moshe; Espinoza, Jimmy; Yoon, Bo Hyun; Hassan, Sonia S.

    2008-01-01

    Aims Adiponectin is an adipokine with insulin-sensitizing, anti-atherogenic, anti-inflammatory and angiogenic properties. The aims of this study were to determine whether maternal plasma adiponectin concentrations differ between patients with severe preeclampsia and those with normal pregnancies, and to explore the relationship between plasma adiponectin and the results of Doppler velocimetry of the uterine arteries. Methods This case-control study included two groups: (1) patients with severe preeclampsia (n=50) and (2) patients with normal pregnancies (n=150). Pulsed-wave and color Doppler ultrasound examination of the uterine arteries were performed. Plasma adiponectin concentrations were determined by ELISA. Non-parametric statistics were used for analysis. Results (1) Patients with severe preeclampsia had a higher median plasma concentration of adiponectin than that of normal pregnant women. (2) The median plasma adiponectin concentration did not differ between women with severe preeclampsia who had a high impedance to blood flow in the uterine arteries and those with normal impedance to blood flow. (3) Among patients with normal pregnancies, plasma adiponectin concentrations were negatively correlated with BMI in the first trimester and at sampling. Conclusions Women with severe preeclampsia have a higher median plasma concentration of adiponectin than that of normal pregnant women. This may reflect a compensatory feedback mechanism to the metabolically-altered, anti-angiogenic and pro-atherogenic state of severe preeclampsia. PMID:17919115

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

    PubMed Central

    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. PMID:28178338

  15. Variants of the Adiponectin (ADIPOQ) and Adiponectin Receptor 1 (ADIPOR1) Genes and Colorectal Cancer Risk

    PubMed Central

    Kaklamani, Virginia G.; Wisinski, Kari B.; Sadim, Maureen; Gulden, Cassandra; Do, Albert; Offit, Kenneth; Baron, John A.; Ahsan, Habibul; Mantzoros, Christos; Pasche, Boris

    2008-01-01

    Context Current epidemiological evidence suggests an association between obesity, hyperinsulinemia, and colorectal cancer risk. Adiponectin is a hormone secreted by the adipose tissue, and serum levels are inversely correlated with obesity and hyperinsulinemia. While there is evidence of an association between circulating adiponectin levels and colorectal cancer risk, no association between genes of the adiponectin pathway and colorectal cancer have been reported to date. Objective To determine the association of 10 haplotype-tagging single-nucleotide polymorphisms (SNPs) of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes with colorectal cancer risk. Design, Setting, and Patients Two case-control studies including patients with a diagnosis of colorectal cancer and controls were recruited between 2000 and 2007. Case-control study 1 included a total of 441 patients with a diagnosis of colorectal cancer and 658 controls; both groups were of Ashkenazi Jewish ancestry and from New York, New York. Case-control study 2 included 199 patients with a diagnosis of colorectal cancer and 199 controls from Chicago, Illinois, matched 1:1 for sex, age, and ethnicity. Main Outcome Measures ADIPOQ and ADIPOR1 SNP frequency among cases and controls. Results In study 1, after adjustment for age, sex, and SNPs from the same gene, 3 ADIPOQ SNPs and 1 ADIPOR1 SNP were associated with colorectal cancer risk: rs266729 (adjusted odds ratio [AOR], 0.72; 95% confidence interval [CI], 0.55–0.95) and rs822396 (AOR, 0.37; 95% CI, 0.14–1.00) were associated with decreased risk whereas rs822395 (AOR, 1.76; 95% CI, 1.09–2.84) and rs1342387 (AOR, 1.79; 95% CI, 1.18–2.72) were associated with increased risk. In study 2, after adjustment for age, sex, race, and SNPs from the same gene, the ADIPOQ SNP rs266729 was associated with a decreased colorectal cancer risk of similar magnitude as in study 1 (AOR, 0.52; 95% CI, 0.34–0.78). Combined analysis of both studies shows an

  16. Low-Grade Metabolically-Induced Inflammation Mediators Interleukin-6, Adiponectin, and TNF-α Serum Levels in Obese Pregnant Patients in the Perinatal Period

    PubMed Central

    Zembala-Szczerba, Małgorzata; Jaworowski, Andrzej; Huras, Hubert; Babczyk, Dorota; Jach, Robert

    2017-01-01

    Background Obesity is a major clinical problem. The number of obese pregnant women is rising rapidly. The consequences of obesity are significant and affect every aspect of perinatal care for both the mother and the developing fetus. Adipose tissue may be responsible for chronic subclinical inflammation in obesity, being a source of inflammatory mediators. The study was designed to evaluate the analysis of the serum concentration of inflammatory mediators, including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and adiponectin, in obese pregnant women at full-term pregnancies. Material/Methods The study included 40 women with body mass index (BMI) less than 30 and 24 pregnant women with BMI equal to or greater than 30, admitted to the Perinatology and Obstetrics Department of the University Hospital in Cracow in the first stage of labor. Blood samples were taken from patients to detect the serum concentration of cytokines. Ultrasound was used to evaluate the development of the fetus, including estimated fetal weight, Doppler flows, and the amount of amniotic fluid. We also included the history of chronic diseases and other complications of the pregnancy. A p-value <0.05 was considered significant. Results The level of adiponectin in obese patients as compared to controls was significantly lower. There was no statistically significant difference in either group when TNF-α and IL-6 were measured. The results of the survey are consistent with previous reports. Conclusions The exact role of inflammation in pregnancy is not well understood. Determining the exact functions of the different cytokines in physiological pregnancy and pregnancy complicated by obesity requires further study. PMID:28077838

  17. Adiponectin, Leptin, and Chemerin in Elderly Patients with Type 2 Diabetes Mellitus: A Close Linkage with Obesity and Length of the Disease

    PubMed Central

    Brandão Proença, Jorge; Neuparth, Maria João

    2014-01-01

    Obesity, insulin resistance, and aging are closely associated and adipokines seem to have a crucial role in their pathophysiology. We aim to study the relationship between aging and chemerin, adiponectin, and leptin levels in type 2 diabetes mellitus (T2DM). Age correlated positively with chemerin and leptin and inversely with adiponectin. Body mass index (BMI) correlated positively with leptin (in males) and chemerin and inversely with adiponectin. The patients with ≥65 years (n = 34) showed significantly higher leptin and chemerin and lower adiponectin levels than middle-aged (38–64 years) patients (n = 39) and controls (n = 20). After statistical adjustment for length of disease, there was a loss of significance, between T2DM groups, for adiponectin and, in female, for leptin. In the older group, BMI correlated with adiponectin and with leptin, but not with chemerin. Adiponectin and leptin levels in elderly T2DM patients seem to be closely linked to obesity and to length of the disease. In elderly T2DM patients, chemerin concentrations are increased and seem to be independent of length of disease and BMI, suggesting that adipocyte dysfunction is enhanced with aging. The understanding of the glucose homeostasis impairment in the elderly is mandatory in order to achieve ways to improve their quality of life and longevity. PMID:25105135

  18. Adiponectin induces A20 expression in adipose tissue to confer metabolic benefit.

    PubMed

    Hand, Laura E; Usan, Paola; Cooper, Garth J S; Xu, Lance Y; Ammori, Basil; Cunningham, Peter S; Aghamohammadzadeh, Reza; Soran, Handrean; Greenstein, Adam; Loudon, Andrew S I; Bechtold, David A; Ray, David W

    2015-01-01

    Obesity is a major risk factor for metabolic disease, with white adipose tissue (WAT) inflammation emerging as a key underlying pathology. We detail that mice lacking Reverbα exhibit enhanced fat storage without the predicted increased WAT inflammation or loss of insulin sensitivity. In contrast to most animal models of obesity and obese human patients, Reverbα(-/-) mice exhibit elevated serum adiponectin levels and increased adiponectin secretion from WAT explants in vitro, highlighting a potential anti-inflammatory role of this adipokine in hypertrophic WAT. Indeed, adiponectin was found to suppress primary macrophage responses to lipopolysaccharide and proinflammatory fatty acids, and this suppression depended on glycogen synthase kinase 3β activation and induction of A20. Attenuated inflammatory responses in Reverbα(-/-) WAT depots were associated with tonic elevation of A20 protein and ex vivo shown to depend on A20. We also demonstrate that adipose A20 expression in obese human subjects exhibits a negative correlation with measures of insulin sensitivity. Furthermore, bariatric surgery-induced weight loss was accompanied by enhanced WAT A20 expression, which is positively correlated with increased serum adiponectin and improved metabolic and inflammatory markers, including C-reactive protein. The findings identify A20 as a mediator of adiponectin anti-inflammatory action in WAT and a potential target for mitigating obesity-related pathology.

  19. High serum adiponectin predicts incident fractures in elderly men: Osteoporotic fractures in men (MrOS) Sweden.

    PubMed

    Johansson, Helena; Odén, Anders; Lerner, Ulf H; Jutberger, Hans; Lorentzon, Mattias; Barrett-Connor, Elizabeth; Karlsson, Magnus K; Ljunggren, Osten; Smith, Ulf; McCloskey, Eugene; Kanis, John A; Ohlsson, Claes; Mellström, Dan

    2012-06-01

    Adipocytes and osteoblasts share a common progenitor, and there is, therefore, potential for both autocrine and endocrine effects of adiponectin on skeletal metabolism. The aim of the present study was to determine whether high serum adiponectin was associated with an increased risk of fracture in elderly men. We studied the relationship between serum adiponectin and the risk of fracture in 999 elderly men drawn from the general population and recruited to the Osteoporotic Fractures in Men (MrOS) study in Gothenburg, Sweden. Baseline data included general health questionnaires, lifestyle questionnaires, body mass index (BMI), bone mineral density (BMD), serum adiponectin, osteocalcin, and leptin. Men were followed for up to 7.4 years (average, 5.2 years). Poisson regression was used to investigate the relationship between serum adiponectin, other risk variables and the time-to-event hazard function of fracture. Median levels of serum adiponectin at baseline were 10.4 µg/mL (interquartile range, 7.7-14.3). During follow-up, 150 men sustained one or more fractures. The risk of fracture increased in parallel with increasing serum adiponectin (hazard ratio [HR]/SD, 1.46; 95% confidence interval [CI], 1.23-1.72) and persisted after multivariate-adjusted analysis (HR/SD, 1.30; 95% CI, 1.09-1.55). Serum adiponectin shows graded stepwise association with a significant excess risk of fracture in elderly men that was independent of several other risk factors for fracture. Its measurement holds promise as a risk factor for fracture in men.

  20. Uncovering Adiponectin Replenishing Property of Sujiaonori Algal Biomaterial in Humans.

    PubMed

    Ngatu, Nlandu Roger; Ikeda, Mitsunori; Watanabe, Hiroyuki; Tanaka, Mamoru; Inoue, Masataka; Kanbara, Sakiko; Nojima, Sayumi

    2017-02-08

    The replenishment of adiponectin-an adipocyte-derived hormone with salutary health effects-has recently been proposed as a new approach to treat hypertension, also ameliorate cardiovascular and metabolic risks. We conducted a prospective placebo-controlled, non-randomized and investigator-blinded dietary intervention study to evaluate the health effects of dietary intake of Sujiaonori (Ulva/Enteromorpha prolifera Müller) algal biomaterial (SBM), especially on adiponectin production, blood pressure (BP), and body mass index (BMI) in human subjects. Participants (N = 32) were divided into two equally sized groups (n = 16 for each group): SBM group (subjects supplemented with 3 g SBM powder twice a day during meal) and the control group (subjects who took 3 g of a supplement made of 70% corn starch powder and 30% spinach twice a day) for four weeks. Two health survey questionnaires (dietary and current health questionnaires) were completed anonymously, saliva sampling was done for adiponectin measurement by ELISA, and blood pressure (BP) and anthropometric parameters were measured at baseline and four weeks later. Student paired t-test was performed to compare baseline and post-intervention data on outcome variables between the two study groups. Results showed a 2.24-fold increase in adiponectin level in SBM group (2.81 and 6.26 ng/mL at baseline and at the end of study, respectively) (p < 0.01); whereas no significant change was observed in controls (3.58 and 3.51 ng/mL, respectively) (p > 0.05). In SBM subjects, an improvement of BP profile was noted with a significant decrease in systolic BP (p < 0.01). A positive correlation was found between SBM supplementation and adiponectin level, whereas an inverse correlation was noted between SBM supplementation and blood pressure, and also BMI. These findings suggest that SBM-increased adiponectin level and improved BP in a sample of Japanese young adults, and has the potential to improve blood pressure in humans.

  1. Expression of adiponectin receptors in mouse adrenal glands and the adrenocortical Y-1 cell line: adiponectin regulates steroidogenesis.

    PubMed

    Li, Ping; Sun, Fei; Cao, Huang-Ming; Ma, Qin-Yun; Pan, Chun-Ming; Ma, Jun-Hua; Zhang, Xiao-Na; Jiang, He; Song, Huai-Dong; Chen, Ming-Dao

    2009-12-25

    Obesity is frequently associated with malfunctions of the hypothalamus-pituitary-adrenal (HPA) axis and hyperaldosteronism, but the mechanism underlying this association remains unclear. Since the adrenal glands are embedded in adipose tissue, direct cross-talk between adipose tissue and the adrenal gland has been proposed. A previous study found that adiponectin receptor mRNA was expressed in human adrenal glands and aldosterone-producing adenoma (APA). However, the expression of adiponectin receptors in adrenal glands has not been confirmed at the protein level or in other species. Furthermore, it is unclear whether adiponectin receptors expressed in adrenal cells are functional. We found, for the first time, that adiponectin receptor (AdipoR1 and AdipoR2) mRNA and protein were expressed in mouse adrenal and adrenocortical Y-1 cells. However, adiponectin itself was not expressed in mouse adrenal or Y-1 cells. Furthermore, adiponectin acutely reduced basal levels of corticosterone and aldosterone secretion. ACTH-induced steroid secretion was also inhibited by adiponectin, and this was accompanied by a parallel change in the expression of the key genes involved in steroidogenesis. These findings indicate that adiponectin may take part in the modulation of steroidogenesis. Thus, adiponectin is likely to have physiological and/or pathophysiological significance as an endocrine regulator of adrenocortical function.

  2. Cord blood resistin and adiponectin in term newborns of diabetic mothers

    PubMed Central

    Mohamed, Maha H.; Gad, Ghada I.; Ibrahim, Hala Y.; El Shemi, Mohamed S.; Atef, Shereen H.; Ramadan, Naglaa M.; El Saeid, Shimaa M.

    2010-01-01

    Introduction Adipose tissue can release hormones into the blood stream in response to specific extracellular stimuli or changes in metabolic status. Resistin, an adipose-secreted factor, is primarily involved in the modulation of insulin sensitivity and adipocyte differentiation. Adiponectin, an adipocyte-specific hormone with insulin sensitizing, anti-inflammatory and anti-atherogenic effects, is reduced in obesity and type II diabetes. The aim of the study was to assess the influence of maternal pre-existing diabetes on cord blood resistin and adiponectin at birth in relation to neonatal anthropometric parameters and cord blood insulin levels. Material and methods A total of 60 term newborns were prospectively enrolled and categorized into three groups: 20 were macrosomic infants of pre-gestational diabetic mothers (group I), 20 were non-macrosomic infants of pre-gestational diabetic mothers (group II) and 20 were healthy non-macrosomic infants born to non-diabetic mothers serving as controls (group III). Infants’ anthropometric indices were recorded. Cord blood samples for glucose, insulin, resistin and adiponectin assay, together with maternal glycosylated haemoglobin were obtained. Results Serum insulin was increased while resistin and adiponectin were significantly decreased in infants of diabetic mothers (IDMs) compared to the control group. Serum glucose, insulin, resistin and adiponectin were comparable in group I and II. Cord serum resistin correlated positively with cord blood glucose in IDMs in both macrosomic and non-macrosomic groups. Cord serum insulin correlated positively with triceps skinfold thickness in all studied neonates. Cord serum resistin and adiponectin showed no correlation with neonatal anthropometric indices. Multiple regression analysis demonstrated that insulin, resistin and adiponectin together were highly correlated with birth weight, with adiponectin as the one responsible for this positive correlation. Conclusions Infants of

  3. 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.

  4. Correlation of Adiponectin mRNA Abundance and Its Receptors with Quantitative Parameters of Sperm Motility in Rams

    PubMed Central

    Kadivar, Ali; Heidari Khoei, Heidar; Hassanpour, Hossein; Golestanfar, Arefe; Ghanaei, Hamid

    2016-01-01

    Background Adiponectin and its receptors (AdipoR1 and AdipoR2), known as adiponectin system, have some proven roles in the fat and glucose metabolisms. Several studies have shown that adiponectin can be considered as a candidate in linking metabolism to testicular function. In this regard, we evaluated the correlation between sperm mRNA abundance of adiponectin and its receptors, with sperm motility indices in the present study. Materials and Methods In this completely randomized design study, semen samples from 6 adult rams were fractionated on a two layer discontinuous percoll gradient into high and low motile sperm cells, then quantitative parameters of sperm motility were determined by computer-assisted sperm analyzer (CASA). The mRNA abundance levels of Adiponectin, AdipoR1 and AdipoR2 were measured quantitatively using real-time reverse transcriptase polymerase chain reaction (qRT-PCR) in the high and low motile groups. Results Firstly, we showed that adiponectin and its receptors (AdipoR1 and AdipoR2) were transcriptionally expressed in the ram sperm cells. Using Pfaff based method qRT- PCR, these levels of transcription were significantly higher in the high motile rather than low motile samples. This increase was 3.5, 3.6 and 2.5 fold change rate for Adiponectin, AdipoR1 and AdipoR2, respectively. Some of sperm motility indices [curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity (VAP), linearity (LIN), wobble (WOB) and straightness (STR)] were also significantly correlated with Adiponectin and AdipoR1 relative expression. The correlation of AdipoR2 was also significant with the mentioned parameters, although this correlation was not comparable with adiponectin and AdipoR1. Conclusion This study revealed the novel association of adiponectin system with sperm motility. The results of our study suggested that adiponectin is one of the possible factors which can be evaluated and studied in male infertility disorders. PMID:27123210

  5. Circadian expression of adiponectin and its receptors in human adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  6. Serum 25-Hydroxyvitamin D Levels, phosphoprotein enriched in diabetes gene product (PED/PEA-15) and leptin-to-adiponectin ratio in women with PCOS

    PubMed Central

    2011-01-01

    Background Polycystic ovary syndrome (PCOS) is frequently associated with hypovitaminosis D. Vitamin D is endowed with pleiotropic effects, including insulin resistance (IR) and apoptotic pathway. Disruption of the complex mechanism that regulated ovarian apoptosis has been reported in PCOS. Phosphoprotein enriched in diabetes gene product (PED/PEA-15), an anti-apoptotic protein involved in type 2 diabetes mellitus (T2DM), is overexpressed in PCOS women, independently of obesity. Leptin-to-adiponectin ratio (L/A) is a biomarker of IR and low-grade inflammation in PCOS. The aim of the study was to investigate the levels of 25-hydroxy vitamin D (25(OH)D), and L/A, in association with PED/PEA-15 protein abundance, in both lean and overweight/obese (o/o) women with PCOS. Patients and Methods PED/PEA-15 protein abundance and circulating levels of 25(OH)D, L/A, sex hormone-binding globulin, and testosterone were evaluated in 90 untreated PCOS patients (25 ± 4 yrs; range 18-34) and 40 healthy controls age and BMI comparable, from the same geographical area. FAI (free androgen index) and the homeostasis model assessment of insulin resistance (HoMA-IR) index were calculated. Results In o/o PCOS, 25(OH)D levels were significantly lower, and L/A values were significantly higher than in lean PCOS (p < 0.001), while there were no differences in PED/PEA-15 protein abundance. An inverse correlation was observed between 25(OH)D and BMI, PED/PEA-15 protein abundance, insulin, HoMA-IR, FAI (p < 0.001), and L/A (p < 0.05). At the multivariate analysis, in o/o PCOS L/A, insulin and 25(OH)D were the major determinant of PED/PEA-15 protein abundance (β = 0.45, β = 0.41, and β = -0.25, respectively). Conclusions Lower 25(OH)D and higher L/A were associated to PED/PEA-15 protein abundance in PCOS, suggesting their involvement in the ovarian imbalance between pro-and anti-apoptotic mechanisms, with high L/A and insulin and low 25(OH)D levels as the main determinants of PED/PEA-15

  7. Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells

    SciTech Connect

    Dieudonne, Marie-Noelle; Bussiere, Marianne; Dos Santos, Esther; Leneveu, Marie-Christine; Giudicelli, Yves . E-mail: biochip@wanadoo.fr; Pecquery, Rene

    2006-06-23

    It is well established that obesity is a risk factor for breast cancer and that blood levels of adiponectin, a hormone mainly secreted by white adipocytes, are inversely correlated with the body fat mass. As adiponectin elicits anti-proliferative effects in some cell types, we tested the hypothesis that adiponectin could influence human breast cancer MCF-7 cell growth. Here we show that MCF-7 cells express adiponectin receptors and respond to human recombinant adiponectin by reducing their growth, AMPkinase activation, and p42/p44 MAPkinase inactivation. Further, we demonstrate that the anti-proliferative effect of adiponectin involves activation of cell apoptosis and inhibition of cell cycle. These findings suggest that adiponectin could act in vivo as a paracrine/endocrine growth inhibitor towards mammary epithelial cells. Moreover, adipose adiponectin production being strongly reduced in obesity, this study may help to explain why obesity is a risk factor of developing breast cancers.

  8. Adiponectin plays an important role in efficient energy usage under energy shortage.

    PubMed

    Saito, Kiyomi; Arata, Satoru; Hosono, Tomohiko; Sano, Yoshihiro; Takahashi, Katsuhiko; Choi-Miura, Nam-Ho; Nakano, Yasuko; Tobe, Takashi; Tomita, Motowo

    2006-07-01

    Adiponectin is an adipose tissue-specific secretory protein known to be an insulin-sensitizing protein. In this study, we generated adiponectin sense and antisense transgenic (Tg) mice to investigate whether adiponectin plays a role in the regulation of energy homeostasis during the growth stage. Spontaneous motor activity of antisense Tg mice were markedly reduced during fasting, particularly in young female mice, compared with wild type (Wt) and sense Tg mice. Furthermore, both body weight and adipose tissue mass of the antisense female Tg mice drastically reduced during fasting. To examine the relationship between the collapse of abdominal white adipose tissue (WAT) and serum adiponectin level, we measured the expression of genes related to energy expenditure, such as uncoupling protein (UCP). Notably, the mRNA of UCP1 in the WAT of antisense Tg female mice was markedly less than that of Wt mice and the UCP1 mRNA was strongly increased during fasting. These findings suggest that the serum adiponectin is important to maintaining energy homeostasis under energy shortage conditions, such as over female pubertal development.

  9. Adiponectin gene variant interacts with fish oil supplementation to influence serum adiponectin in older individuals.

    PubMed

    Alsaleh, Aseel; Crepostnaia, Daria; Maniou, Zoitsa; Lewis, Fiona J; Hall, Wendy L; Sanders, Thomas A B; O'Dell, Sandra D

    2013-07-01

    Marine n3 polyunsaturated fatty acids (PUFAs) activate the transcription factor peroxisome proliferator-activated receptor (PPARγ), which modulates the expression of adiponectin. We investigated the interaction of dietary n3 PUFAs with adiponectin gene (ADIPOQ) single nucleotide polymorphism (SNP) genotypes as a determinant of serum adiponectin concentration. The Modulation of Atherosclerosis Risk by Increasing Doses of n3 Fatty Acids study is a parallel design, double-blind, controlled trial. Serum adiponectin was measured in 142 healthy men and 225 women aged 45-70 y randomized to treatment with doses of 0.45, 0.9, and 1.8 g/d 20:5n3 and 22:6n3 (1.51:1), or placebo for 12 mo. The 310 participants who completed the study were genotyped for 5 SNPs at the ADIPOQ locus: -11391 G/A (rs17300539), -11377 C/G (rs266729), -10066 G/A (rs182052), +45 T/G (rs2241766), and +276 G/T (rs1501299). The -11391 A-allele was associated with a higher serum adiponectin concentration at baseline (n = 290; P < 0.001). The interaction between treatment and age as a determinant of adiponectin was significant in participants aged >58 y after the highest dose (n = 92; P = 0.020). The interaction between +45 T/G and treatment and age was a nominally significant determinant of serum adiponectin after adjustment for BMI, gender, and ethnicity (P = 0.029). Individuals homozygous for the +45 T-allele aged >58 y had a 22% increase in serum adiponectin concentration compared with baseline after the highest dose (P-treatment effect = 0.008). If substantiated in a larger sample, a diet high in n3 PUFAs may be recommended for older individuals, especially those of the +45 TT genotype who have reported increased risk of hypoadiponectinemia, type 2 diabetes, and obesity.

  10. Adiponectin and Insulin in Gray Seals during Suckling and Fasting: Relationship with Nutritional State and Body Mass during Nursing in Mothers and Pups.

    PubMed

    Bennett, K A; Hughes, J; Stamatas, S; Brand, S; Foster, N L; Moss, S E W; Pomeroy, P P

    2015-01-01

    Animals that fast during breeding and/or development, such as phocids, must regulate energy balance carefully to maximize reproductive fitness and survival probability. Adiponectin, produced by adipose tissue, contributes to metabolic regulation by modulating sensitivity to insulin, increasing fatty acid oxidation by liver and muscle, and promoting adipogenesis and lipid storage in fat tissue. We tested the hypotheses that (1) circulating adiponectin, insulin, or relative adiponectin gene expression is related to nutritional state, body mass, and mass gain in wild gray seal pups; (2) plasma adiponectin or insulin is related to maternal lactation duration, body mass, percentage milk fat, or free fatty acid (FFA) concentration; and (3) plasma adiponectin and insulin are correlated with circulating FFA in females and pups. In pups, plasma adiponectin decreased during suckling (linear mixed-effects model [LME]: T = 4.49; P < 0.001) and the early postweaning fast (LME: T = 3.39; P = 0.004). In contrast, their blubber adiponectin gene expression was higher during the early postweaning fast than early in suckling (LME: T = 2.11; P = 0.046). Insulin levels were significantly higher in early (LME: T = 3.52; P = 0.004) and late (LME: T = 6.99; P < 0.001) suckling than in fasting and, given the effect of nutritional state, were also positively related to body mass (LME: T = 3.58; P = 0.004). Adiponectin and insulin levels did not change during lactation and were unrelated to milk FFA or percentage milk fat in adult females. Our data suggest that adiponectin, in conjunction with insulin, may facilitate fat storage in seals and is likely to be particularly important in the development of blubber reserves in pups.

  11. A common variant in the CLDN7/ELP5 locus predicts adiponectin change with lifestyle intervention and improved fitness in obese individuals with diabetes

    PubMed Central

    Papandonatos, George D.; McCaffery, Jeanne M.; Peter, Inga; Pajewski, Nicholas M.; Erar, Bahar; Allred, Nicholette D.; Balasubramanyam, Ashok; Bowden, Donald W.; Brautbar, Ariel; Pi-Sunyer, F. Xavier; Ballantyne, Christie M.; Huggins, Gordon S.

    2015-01-01

    Overweight/obese individuals with Type 2 diabetes have low adiponectin levels, which may improve with lifestyle changes. We investigated whether genetic variants associated with adiponectin levels in genome-wide association studies (GWAS) would also be related with adiponectin changes in response to an intensive lifestyle intervention (ILI), potentially through mechanisms altering the adipose microenvironment via weight loss and/or improved cardiorespiratory fitness. Look AHEAD was a randomized trial comparing the cardiovascular benefits of ILI-induced weight loss and physical activity compared with diabetes support and education among overweight/obese individuals with Type 2 diabetes. In a subsample of Look AHEAD with adiponectin data and genetic consent (n = 1,351), we evaluated the effects of 24 genetic variants, demonstrated by GWAS to be cross-sectionally associated with adiponectin, on adiponectin change 1-yr postintervention. We explored via mediational analyses whether any differential effects by treatment arm were occurring through weight loss and/or improved fitness. A variant, rs222857, in the CLDN7 locus, potentially associated with epithelial barrier integrity and tight junction physiology, and a putative cis expression quantitative trail locus for elongator acetyltransferase complex subunit 5 (ELP5), predicted adiponectin increases within ILI (log-adiponectin in overall sample per copy: β ± SE = 0.05 ± 0.02, P = 0.008; in non-Hispanic whites: 0.06 ± 0.02, P = 0.009). The favorable effects of rs222857 (minor allele frequency 45.5%) appeared to be mediated by mechanisms associated with improved fitness, and not weight loss. This is the first study to identify a genetic variant that modifies adiponectin response to lifestyle intervention in overweight/obese diabetic individuals. PMID:25759378

  12. Ethnicity Modifies the Relationships of Insulin Resistance, Inflammation, and Adiponectin With Obesity in a Multiethnic Asian Population

    PubMed Central

    Khoo, Chin Meng; Sairazi, Sarina; Taslim, Siska; Gardner, Daphne; Wu, Yi; Lee, Jeannette; van Dam, Rob M.; Shyong Tai, E.

    2011-01-01

    OBJECTIVE The development of obesity-related metabolic disorders varies with ethnicity. We examined whether ethnicity modifies the relationship between BMI and three metabolic pathways (insulin resistance, inflammation, and adiponectin) that are involved in the pathogenesis of diabetes and cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS We analyzed data from 4,804 Chinese, Malay, and Asian-Indian residents of Singapore with complete data on insulin resistance (IR), C-reactive protein (CRP), and total adiponectin levels. Linear regression models with an interaction term ethnicity*BMI were used to evaluate whether ethnicity modifies the association between BMI and IR, CRP, and adiponectin. RESULTS In both uni- and multivariate analyses, BMI was directly associated with IR and CRP and inversely with adiponectin across all ethnic groups. When compared with Chinese and Malays, Asian-Indians had higher IR and CRP and lower adiponectin levels. The associations between BMI and its metabolic pathways were significantly stronger in Chinese than in other ethnic groups. The increase in IR and CRP and the decrease in adiponectin for each unit increase in BMI were greater in Chinese than in other ethnic groups. The findings were similar when waist circumference was used in the analyses instead of BMI. CONCLUSIONS The impact of BMI on IR, CRP, and adiponectin appears greater in Chinese as compared with other major Asian ethnic groups. This may partly explain the rapid increase in the prevalence of diabetes and CVD in Chinese populations and highlights the importance of weight management in Asian ethnic groups despite the apparently low levels of obesity. PMID:21464462

  13. 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.

  14. The Balance between Leptin and Adiponectin in the Control of Carcinogenesis- Focus on Mammary Tumorigenesis

    PubMed Central

    Grossmann, Michael E.

    2013-01-01

    A number of studies indicate that a growing list of cancers may be influenced by obesity. In obese individuals these cancers can be more frequent and more aggressive resulting in reduced survival. One of the most prominent and well characterized cancers in this regard is breast cancer. Obesity plays a complex role in breast cancer and is associated with increased inflammation, angiogenesis and alterations in serum levels of potential growth factors such as adiponectin, leptin and estrogen in the serum. Reduced levels of serum adiponectin have been reported in breast cancer patients compared to healthy controls, particularly in postmenopausal women. The role of serum leptin levels in breast cancer appears to be more complex. Some studies have shown leptin to be increased in women with breast cancer but other studies have found leptin to be decreased or unchanged. This may be due to a number of confounding issues. We and others propose that it may be the levels of adiponectin and leptin as well as the balance of adiponectin and leptin that are the critical factors in breast and other obesity related cancer tumorigenesis. PMID:22728769

  15. Serum high-molecular weight adiponectin decreases abruptly after an oral glucose load in subjects with normal glucose tolerance or impaired fasting glucose, but not those with impaired glucose tolerance or diabetes mellitus.

    PubMed

    Ozeki, Noriyuki; Hara, Kenji; Yatsuka, Chikako; Nakano, Tomoki; Matsumoto, Sachiko; Suetsugu, Mariko; Nakamachi, Takafumi; Takebayashi, Kohzo; Inukai, Toshihiko; Haruki, Kohsuke; Aso, Yoshimasa

    2009-10-01

    Adiponectin exists in the blood as 3 forms, which are a trimer, a hexamer, and a high-molecular weight (HMW) form. We investigated whether circulating HMW adiponectin levels were altered by oral glucose or fat ingestion. Forty male subjects underwent a 75-g oral glucose loading test (OGTT), and 11 healthy subjects (5 women and 6 men) received a fat loading test. Serum levels of HMW and total adiponectin were measured during the OGTT and the fat loading test. The fat loading test was performed for at least 8 hours. Among the 40 male subjects, 11 had normal glucose tolerance (NGT), 9 had impaired fasting glucose (IFG), 11 had impaired glucose tolerance, and 9 had diabetes mellitus (DM). In all 40 subjects, the serum total adiponectin level did not change significantly, whereas serum HMW adiponectin decreased significantly after a glucose load and reached 92.2% of the basal level at 120 minutes after the OGTT (P < .01). The HMW to total adiponectin ratio decreased significantly from 0.47 +/- 0.15 at baseline to 0.43 +/- 0.13 at 120 minutes after a glucose load (P < .05). Serum HMW adiponectin measured at 120 minutes after the OGTT decreased significantly to 86.0% and 85.6% of the basal level in subjects with NGT or IFG, respectively (both P < .01). In subjects with impaired glucose tolerance or DM, however, serum HMW adiponectin did not change. The area under the curve for insulin at 30 minutes after a glucose load during the OGTT was significantly larger in subjects with NGT or IFG than in those with DM (P < .05). In addition, the insulinogenic index (DeltaI(0-30)/DeltaG(0-30)) was significantly higher in subjects with NGT or IFG than in those with DM (P < .001). Percentage changes in serum HMW adiponectin of the baseline at 120 minutes correlated negatively with those in serum insulin (r = -0.468, P = .0023), but not plasma glucose, of the baseline at 30 minutes in 40 subjects. On the other hand, serum triglycerides increased significantly after an oral fat load in

  16. Circulating leptin and adiponectin concentrations in healthy exceptional longevity.

    PubMed

    Pareja-Galeano, Helios; Santos-Lozano, Alejandro; Sanchis-Gomar, Fabian; Fiuza-Luces, Carmen; Garatachea, Nuria; Gálvez, Beatriz G; Lucia, Alejandro; Emanuele, Enzo

    2017-03-01

    People reaching exceptional longevity free of major age-related diseases represent the paradigm of successful aging. Adipose tissue function declines as we age, potentially resulting in changes of circulating adipokines (e.g., leptin and adiponectin). Here, we measured circulating levels of leptin and adiponectin in healthy centenarians (n=81; 100-104 years) and younger elderly controls (n=46; 70-80 years). Centenarians had significant higher serum levels of leptin compared with controls (p<0.001), whereas no significant differences were observed for adiponectin. Further research including also other blood variables will be needed to elucidate whether high leptin levels could serve as a hallmark of healthy exceptional longevity.

  17. Uncovering Adiponectin Replenishing Property of Sujiaonori Algal Biomaterial in Humans

    PubMed Central

    Ngatu, Nlandu Roger; Ikeda, Mitsunori; Watanabe, Hiroyuki; Tanaka, Mamoru; Inoue, Masataka; Kanbara, Sakiko; Nojima, Sayumi

    2017-01-01

    The replenishment of adiponectin—an adipocyte-derived hormone with salutary health effects—has recently been proposed as a new approach to treat hypertension, also ameliorate cardiovascular and metabolic risks. We conducted a prospective placebo-controlled, non-randomized and investigator-blinded dietary intervention study to evaluate the health effects of dietary intake of Sujiaonori (Ulva/Enteromorpha prolifera Müller) algal biomaterial (SBM), especially on adiponectin production, blood pressure (BP), and body mass index (BMI) in human subjects. Participants (N = 32) were divided into two equally sized groups (n = 16 for each group): SBM group (subjects supplemented with 3 g SBM powder twice a day during meal) and the control group (subjects who took 3 g of a supplement made of 70% corn starch powder and 30% spinach twice a day) for four weeks. Two health survey questionnaires (dietary and current health questionnaires) were completed anonymously, saliva sampling was done for adiponectin measurement by ELISA, and blood pressure (BP) and anthropometric parameters were measured at baseline and four weeks later. Student paired t-test was performed to compare baseline and post-intervention data on outcome variables between the two study groups. Results showed a 2.24-fold increase in adiponectin level in SBM group (2.81 and 6.26 ng/mL at baseline and at the end of study, respectively) (p < 0.01); whereas no significant change was observed in controls (3.58 and 3.51 ng/mL, respectively) (p > 0.05). In SBM subjects, an improvement of BP profile was noted with a significant decrease in systolic BP (p < 0.01). A positive correlation was found between SBM supplementation and adiponectin level, whereas an inverse correlation was noted between SBM supplementation and blood pressure, and also BMI. These findings suggest that SBM-increased adiponectin level and improved BP in a sample of Japanese young adults, and has the potential to improve blood pressure in humans

  18. Adiponectin in mice with altered growth hormone action: links to insulin sensitivity and longevity?

    PubMed Central

    Lubbers, Ellen R.; List, Edward O.; Jara, Adam; Sackman-Sala, Lucila; Cordoba-Chacon, Jose; Gahete, Manuel D.; Kineman, Rhonda D.; Boparai, Ravneet; Bartke, Andrzej; Kopchick, John J.; Berryman, Darlene E.

    2013-01-01

    Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high molecular weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered growth hormone (GH) signaling as these mice exhibit extremes in obesity that are positively associated with insulin sensitivity and lifespan as opposed to the typical negative association of these factors. While a few studies have reported total adiponectin levels in young adult mice with altered GH signaling, much remains unresolved, including changes in adiponectin levels with advancing age, proportion of total adiponectin in the HMW form, adipose depot of origin, and differential effects of GH versus IGF1. Therefore, the purpose of this study was to address these issues using assorted mouse lines with altered GH signaling. Our results show that adiponectin is generally negatively associated with GH activity, regardless of age. Further, the amount of HMW adiponectin is consistently linked with the level of total adiponectin and not necessarily with previously reported lifespan or insulin sensitivity of these mice. Interestingly, circulating adiponectin levels correlated strongly with inguinal fat mass, implying the effects of GH on adiponectin are depot-specific. Interestingly rbGH, but not IGF1, decreased circulating total and HMW adiponectin levels. Taken together, these results fill important gaps in the literature related to GH and adiponectin and question the frequently reported associations of total and HMW adiponectin with insulin sensitivity and longevity. PMID:23261955

  19. Adiponectin in mice with altered GH action: links to insulin sensitivity and longevity?

    PubMed

    Lubbers, Ellen R; List, Edward O; Jara, Adam; Sackman-Sala, Lucila; Cordoba-Chacon, Jose; Gahete, Manuel D; Kineman, Rhonda D; Boparai, Ravneet; Bartke, Andrzej; Kopchick, John J; Berryman, Darlene E

    2013-03-01

    Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high-molecular-weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered GH signaling as these mice exhibit extremes in obesity that are positively associated with insulin sensitivity and lifespan as opposed to the typical negative association of these factors. While a few studies have reported total adiponectin levels in young adult mice with altered GH signaling, much remains unresolved, including changes in adiponectin levels with advancing age, proportion of total adiponectin in the HMW form, adipose depot of origin, and differential effects of GH vs IGF1. Therefore, the purpose of this study was to address these issues using assorted mouse lines with altered GH signaling. Our results show that adiponectin is generally negatively associated with GH activity, regardless of age. Further, the amount of HMW adiponectin is consistently linked with the level of total adiponectin and not necessarily with previously reported lifespan or insulin sensitivity of these mice. Interestingly, circulating adiponectin levels correlated strongly with inguinal fat mass, implying that the effects of GH on adiponectin are depot specific. Interestingly, rbGH, but not IGF1, decreased circulating total and HMW adiponectin levels. Taken together, these results fill important gaps in the literature related to GH and adiponectin and question the frequently reported associations of total and HMW adiponectin with insulin sensitivity and longevity.

  20. Serum adiponectin and leptin concentrations in HIV-infected children with fat redistribution syndrome.

    PubMed

    Verkauskiene, Rasa; Dollfus, Catherine; Levine, Martine; Faye, Albert; Deghmoun, Samia; Houang, Muriel; Chevenne, Didier; Bresson, Jean-Louis; Blanche, Stéphane; Lévy-Marchal, Claire

    2006-08-01

    Human immunodeficiency virus (HIV)-related lipodystrophy is characterized by adipose tissue redistribution, dyslipidemia, and insulin resistance. We hypothesized that fat redistribution and metabolic abnormalities in HIV-infected children are related to alterations in endocrine function of adipose tissue. A multicenter study was conducted in 130 HIV-infected children. Lipodystrophy definition was based on the central to peripheral skinfold ratio. Fasting adiponectin, leptin, insulin concentrations, glycemia, and lipid profile were measured in all children. Fat redistribution syndrome was apparent in 32 children: 14 with atrophic (LPDA) and 18 with hypertrophic lipodystrophy (LPDH). Mean serum adiponectin levels were significantly decreased in LPDA and LPDH groups compared with the group with no lipodystrophy (LPD-). Fasting insulin concentration was significantly higher in LPDA and LPDH groups versus LPD-. Mean serum leptin concentration was significantly increased only in LPDH compared with LPDA and LPD- groups. Triglyceride levels were significantly increased and high-density lipoprotein (HDL)-cholesterol concentration decreased in the LPDA versus LPD- group. Controlling for puberty stage, gender, percentage of total fat mass, serum lipids, HIV treatment, and disease severity, adiponectin was significantly and inversely associated with central obesity and insulin/glucose ratio. Fat redistribution had no significant effect on leptin concentration, which was directly related to the percentage of body fat, female gender, and insulin/glucose ratio. In conclusion, HIV-infected children with symptoms of fat redistribution have decreased levels of adiponectin, associated with insulin resistance and dyslipidemia.

  1. 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.

  2. Role of adiponectin in insulin-resistant hypertension and atherosclerosis.

    PubMed

    Murakami, Hideyuki; Ura, Nobuyuki; Furuhashi, Masato; Higashiura, Katsuhiro; Miura, Tetsuji; Shimamoto, Kazuaki

    2003-09-01

    Insulin resistance is one of the major risk factors associated with development of hypertension and atherosclerosis. Recent studies have shown that adiponectin, an adipocyte-derived hormone, may be involved in insulin resistance and development of atherosclerosis in diabetes patients. The aim of this study was to examine adiponectin levels in patients with essential hypertension to determine the relationships between adiponectin levels and insulin sensitivity and to examine the relationship of adiponectin with pulse wave velocity (PWV) in a general population based on the results of an epidemiological survey in Japan. In a clinical study, 20 normotensives (NT) and 30 non-treated essential hypertensives (EHT) were hospitalized, and euglycemic hyperinsulinemic glucose clamp (GC) was performed to evaluate insulin sensitivity defined as M value. EHT were divided into insulin-resistant EHT (EHT-R) and insulin-nonresistant EHT (EHT-N) according to the mean -1 SD of the M value of NT as a cut-off point. Fasting plasma glucose (FPG), immunoreactive insulin (IRI), and adiponectin concentrations were measured. There were no significant differences in body mass index (BMI) or FPG among the NT, EHT-N, and EHT-R groups. The M value and adiponectin concentration in EHT-R were significantly lower than those in the NT or EHT-N. The IRI level in the EHT-R was significantly higher than those in the other groups. A positive correlation between adiponectin concentration and M value was found in all subjects, and adiponectin concentration and M value were found to be significant determinants of each other in multiple regression analysis. In an epidemiological study, we studied 391 male inhabitants of rural communities in Hokkaido, Japan. Systolic blood pressure (SBP), BMI, FPG, IRI, and adiponectin were measured in all subjects early in the morning. Homeostasis model assessment (HOMA) values were calculated as an index of insulin sensitivity, and PWV was used as an index of

  3. 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

  4. Increased serum resistin levels in patients with type 2 diabetes are not linked with markers of insulin resistance and adiposity.

    PubMed

    Hasegawa, G; Ohta, M; Ichida, Y; Obayashi, H; Shigeta, M; Yamasaki, M; Fukui, M; Yoshikawa, T; Nakamura, N

    2005-06-01

    The role of resistin in human biology remains uncertain. We measured serum resistin levels in Japanese patients with (n=111) and without (n=98) type 2 diabetes mellitus and investigated the significance of this hormone in the pathophysiology of diabetes. The levels of serum adiponectin and leptin were also measured. Resistin levels were increased significantly in patients with type 2 diabetes compared with non-diabetic subjects (24.7+/-2.6 vs. 15.0+/-1.2 ng/ml, p=0.0013). However, there was no correlation in either patient group between serum resistin levels and markers of insulin resistance, obesity or hyperlipidaemia. These results were in direct contrast to the data of leptin or adiponectin, both of which were closely related to these clinical markers of diabetes. Multivariate regression analysis on the combined data of the two groups demonstrated that the presence of diabetes and HDL cholesterol levels were significant predictors of serum resistin levels (diabetes: beta=0.159, p=0.035; HDL: beta=-0.172, p=0.039). No correlation was observed between C-reactive protein and resistin adjusted for BMI. Taken together, these findings demonstrate that serum resistin levels are increased in patients with type 2 diabetes, but this increase is not linked to markers of insulin resistance or adiposity. Further studies are necessary to elucidate the significance of serum resistin concentration in human pathophysiology.

  5. Polymorphism of adiponectin (45T/G) and adiponectin receptor-2 (795G/A) in an Iranian population: relation with insulin resistance and response to treatment with pioglitazone in patients with type 2 diabetes mellitus.

    PubMed

    Namvaran, Fatemeh; Rahimi-Moghaddam, Parvaneh; Azarpira, Negar; Dabbaghmanesh, Mohammad Hosein

    2012-05-01

    Adiponectin, an adipose-derived plasma protein, is reduced in patients with obesity and type 2 diabetes. Thiazolidinediones can increase adiponectin levels and improve insulin sensitivity. This study investigated the associations between type 2 diabetes and two single-nucleotide polymorphisms in the adiponectin (45T/G) and adiponectin receptor-2 gene (795G/A), and investigated whether these genetic variants affect the response to pioglitazone in Iranian patients with type 2 diabetes. We genotyped 128 non-diabetic participants and 101 patients with type 2 diabetes for 45T/G and 795G/A with polymerase chain reaction-restriction fragment length polymorphism assays. Patients were treated with pioglitazone for 12 weeks, after which we compared laboratory parameters in these two groups. Fasting blood sugar differed significantly in individuals with different 795G/A genotypes after pioglitazone treatment (P = 0.009). The mean decrease in insulin/glucose ratio after treatment also differed significantly in individuals with different 45T/G genotypes (P = 0.035). The T allele frequency for 45T/G was 87.11% in controls versus 81.68% in patients (P = 0.071). The TG and GG genotypes were more frequent in patients (P = 0.032). The G allele frequency for 795G/A was 76.17% in controls versus 80.20% in patients (P = 0.179). 795G/A variants were not significantly different between patient and control group. The adiponectin gene 45T/G mutation may be an important determinant of type 2 diabetes in the Iranian population. However, adiponectin 45T/G and adiponectin receptor-2 795G/A polymorphisms were not significantly associated with the response to pioglitazone in our sample.

  6. 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.

  7. Hypoxia-inducible Factor 1α Regulates a SOCS3-STAT3-Adiponectin Signal Transduction Pathway in Adipocytes*

    PubMed Central

    Jiang, Changtao; Kim, Jung-Hwan; Li, Fei; Qu, Aijuan; Gavrilova, Oksana; Shah, Yatrik M.; Gonzalez, Frank J.

    2013-01-01

    Obesity has been identified as a major risk factor for type 2 diabetes, characterized by insulin resistance in insulin target tissues. Hypoxia-inducible factor 1α (HIF1α) regulates pathways in energy metabolism that become dysregulated in obesity. Earlier studies revealed that HIF1α in adipose tissue is markedly elevated in high-fat diet-fed mice that are obese and insulin-resistant. Genetic ablation of HIF1α in adipose tissue decreased insulin resistance and obesity, accompanied by increased serum adiponectin levels. However, the exact mechanism whereby HIF1α regulates adiponectin remains unclear. Here, acriflavine (ACF), an inhibitor of HIF1α, induced the expression of adiponectin and reduced the expression of SOCS3 in cultured 3T3-L1 adipocytes. Mechanistic studies revealed that HIF1α suppressed the expression of adiponectin through a SOCS3-STAT3 pathway. Socs3 was identified as a novel HIF1α target gene based on chromatin immunoprecipitation and luciferase assays. STAT3 directly regulated adiponectin in vitro in cultured 3T3-L1 adipocytes. ACF was found to prevent diet-induced obesity and insulin resistance. In vivo, ACF also regulated the SOCS3-STAT3-adiponectin pathway, and inhibition of HIF1α in adipose tissue was essential for ACF to improve the SOCS3-STAT3-adiponectin pathway to counteract insulin resistance. This study provides evidence for a novel target gene and signal transduction pathway in adipocytes and indicates that inhibitors of HIF1α have potential utility for the treatment of obesity and type 2 diabetes. PMID:23255598

  8. 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.

  9. Regulation of adiponectin in adipocytes upon exposure to HIV-1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  10. Adiponectin, the past two decades

    PubMed Central

    Wang, Zhao V.; Scherer, Philipp E.

    2016-01-01

    Adiponectin is an adipocyte-specific factor, first described in 1995. Over the past two decades, numerous studies have elucidated the physiological functions of adiponectin in obesity, diabetes, inflammation, atherosclerosis, and cardiovascular disease. Adiponectin, elicited through cognate receptors, suppresses glucose production in the liver and enhances fatty acid oxidation in skeletal muscle, which together contribute to a beneficial metabolic action in whole body energy homeostasis. Beyond its role in metabolism, adiponectin also protects cells from apoptosis and reduces inflammation in various cell types via receptor-dependent mechanisms. Adiponectin, as a fat-derived hormone, therefore fulfills a critical role as an important messenger to communicate between adipose tissue and other organs. A better understanding of adiponectin actions, including the pros and cons, will advance our insights into basic mechanisms of metabolism and inflammation, and potentially pave the way toward novel means of pharmacological intervention to address pathophysiological changes associated with diabetes, atherosclerosis, and cardiometabolic disease. PMID:26993047

  11. PLASMA ADIPONECTIN CONCENTRATIONS IN NON PREGNANT, NORMAL PREGNANCY AND OVERWEIGHT PREGNANT WOMEN

    PubMed Central

    Nien, Jyh Kae; Mazaki-Tovi, Shali; Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Gotsch, Francesca; Pineles, Beth L.; Gomez, Ricardo; Edwin, Samuel; Mazor, Moshe; Espinoza, Jimmy; Yoon, Bo Hyun; Hassan, Sonia S.

    2008-01-01

    Aims Adiponectin is an adipokine that has anti-diabetic, anti-atherogenic, anti-inflammatory and angiogenic properties. This hormone has been implicated in both the physiological adaptation to normal pregnancy and obstetrical complications. The aims of this study were to determine normal maternal plasma concentrations of adiponectin throughout gestation and to explore the relationships between plasma adiponectin concentration, pregnancy, and maternal overweight. Study design A cross-sectional study was designed to include normal pregnant women (normal weight and overweight; 11–42 weeks of gestation), and non-pregnant women. Plasma adiponectin concentration was determined by immunoassay. Non-parametric statistics were used for analysis. Results (1) Adiponectin was detectable in the plasma of all patients; (2) there was no significant difference in the median adiponectin concentrations between pregnant and non-pregnant women; (3) plasma adiponectin concentrations were negatively correlated with gestational age only among normal weight pregnant women; and (4) overweight patients had significantly lower adiponectin concentrations than normal weight women. Conclusion Consistent with the increased insulin resistance and weight gain that occur in pregnancy, adiponectin concentrations were negatively correlated with gestational age. The results of this study and the nomogram herein presented can serve as the basis to explore the relationship between adiponectin and pregnancy complications and facilitate the clinical use of this important adipokine. Condensation Plasma adiponectin concentrations decrease with advancing gestational age only in nonobese women. PMID:17919116

  12. 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

  13. Changes of adiponectin oligomer composition by moderate weight reduction.

    PubMed

    Bobbert, Thomas; Rochlitz, Helmut; Wegewitz, Uta; Akpulat, Suzan; Mai, Knut; Weickert, Martin O; Möhlig, Matthias; Pfeiffer, Andreas F H; Spranger, Joachim

    2005-09-01

    Adiponectin affects lipid metabolism and insulin sensitivity. However, adiponectin circulates in three different oligomers that may also have distinct biological functions. We aimed to analyze the role of these oligomers in obesity and lipid metabolism after weight reduction. A total of 17 obese volunteers (15 women and 2 men) participated in a weight reduction program. Individuals were characterized before and after 6 months of a balanced diet. Adiponectin was determined by enzyme-linked immunosorbent assay, and oligomers were detected by nondenaturating Western blot. BMI decreased (35.1 +/- 1.2 to 32.8 +/- 1.1 kg/m(2), P < 0.001), which was associated with an improved metabolite profile. Total adiponectin increased from 5.3 +/- 0.5 to 6.1 +/- 0.6 microg/ml (P = 0.076). High (HMW) and medium molecular weight (MMW) adiponectin oligomers significantly increased during weight reduction (HMW: 0.37 +/- 0.07 to 0.4 +/- 0.08 microg/ml, P = 0.042; MMW: 2.3 +/- 0.2 to 2.9 +/- 0.3 microg/ml, P = 0.007), while low molecular weight (LMW) did not significantly change. Body weight inversely correlated with HMW (r = -0.695, P = 0.002) and positively with LMW (r = 0.579, P = 0.015). Interestingly, HDL cholesterol and HMW were strongly correlated (r = 0.665, P = 0.007). Indeed, HMW and free fatty acids before weight reduction predicted approximately 60% of HDL changes during intervention. In conclusion, weight reduction results in a relative increase of HMW/MMW adiponectin and a reduction of LMW adiponectin. Total adiponectin and especially HMW adiponectin are related to circulating HDL cholesterol.

  14. Pro-insulin, C peptide, glucagon, adiponectin, TNF alpha, AMPK: neglected players in type 2 diabetes mellitus.

    PubMed

    Lele, R D

    2010-01-01

    This article emphasizes (1) the utility of routine measurement of pro-insulin to insulin ratio as a specific marker of insulin resistance and predictor of future T2DM, HT and CAD, (2) routine C-Peptide estimation to determine which T2DM needs insulin and to monitor the effect of newer drugs which promote beta cell regeneration, (3) routine estimation of adiponectin and TNF alpha and monitor response to thiozolidine drugs which increases adiponectin and decreases TNF alpha production by adipocytes, (4) crucial role of AMPK--Cellular energy sensor in mediating the beneficial effects of exercise as well as drugs (adiponectin, metformin) in T2DM, (5) Availability of glucogon suppressors will eliminate the need for giving insulin to T2 DM with normal C Pepetide levels which inevitably causes undesirable weight gain & hypoglycemia.

  15. 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

  16. Association of adiponectin multimers with Barrett’s oesophagus

    PubMed Central

    Rubenstein, J H; Kao, J Y; Madanick, R D; Zhang, M; Wang, M; Spacek, M B; Donovan, J L; Bright, S D; Shaheen, N J

    2012-01-01

    Objective Barrett’s oesophagus is associated with abdominal obesity. Adiponectin is a peptide that is secreted from adipocytes and circulates in three multimeric forms: low molecular weight (LMW), middle molecular weight (MMW), and high molecular weight (HMW). The anti-inflammatory effects of adiponectin are specific to individual multimers, with LMW being most anti-inflammatory. We postulated that circulating levels of adiponectin and its multimers would be associated with the risk of Barrett’s oesophagus. Design Cross-sectional study. Setting Outpatient clinic in North Carolina, USA. Patients Cases of Barrett’s oesophagus and controls undergoing upper endoscopy for gastro-oesophageal reflux disease (GORD). Main outcome measures Adjusted odds ratios of plasma adiponectin levels and its multimers for Barrett’s oesophagus. Results There were 112 cases of Barrett’s oesophagus and 199 GORD controls. Total adiponectin was not associated with Barrett’s oesophagus (3rd tertile vs 1st tertile adjusted odds ratio (aOR) = 0.88; 95% confidence interval (CI) = 0.44 to 1.78). High levels of LMW adiponectin were associated with a decreased risk of Barrett’s oesophagus (3rd tertile vs 1st tertile aOR = 0.33; 95% CI, 0.16 to 0.69), and a high LMW/total ratio appeared particularly inversely associated with Barrett’s oesophagus (3rd tertile vs 1st tertile aOR = 0.27; 95% CI, 0.13 to 0.58). Conclusions High levels of LMW adiponectin are associated with a decreased risk of Barrett’s oesophagus among patients with GORD. Further human studies are required to confirm these findings, and in vitro studies are needed to understand if there is a mechanism whereby adiponectin may affect Barrett’s metaplasia. PMID:19570765

  17. Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes

    SciTech Connect

    Chen Baoying; Lam, Karen S.L.; Wang Yu; Wu Donghai; Lam, Michael C.; Shen Jiangang; Wong Laiching; Hoo, Ruby L.C.; Zhang Jialiang; Xu Aimin . E-mail: amxu@hkucc.hku.hk

    2006-03-10

    Low plasma levels of adiponectin (hypoadiponectinemia) and elevated circulating concentrations of plasminogen activator inhibitor (PAI)-1 are causally associated with obesity-related insulin resistance and cardiovascular disease. However, the mechanism that mediates the aberrant production of these two adipokines in obesity remains poorly understood. In this study, we investigated the effects of hypoxia and reactive oxygen species (ROS) on production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Quantitative PCR and immunoassays showed that ambient hypoxia markedly suppressed adiponectin mRNA expression and its protein secretion, and increased PAI-1 production in mature adipocytes. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1{alpha} (HIF-1{alpha}), mimicked the hypoxia-mediated modulations of these two adipokines. Hypoxia caused a modest elevation of ROS in adipocytes. However, ablation of intracellular ROS by antioxidants failed to alleviate hypoxia-induced aberrant production of adiponectin and PAI-1. On the other hand, the antioxidants could reverse hydrogen peroxide (H{sub 2}O{sub 2})-induced dysregulation of adiponectin and PAI-1 production. H{sub 2}O{sub 2} treatment decreased the expression levels of peroxisome proliferator-activated receptor gamma (PPAR{gamma}) and CCAAT/enhancer binding protein (C/EBP{alpha}), but had no effect on HIF-1{alpha}, whereas hypoxia stabilized HIF-1{alpha} and decreased expression of C/EBP{alpha}, but not PPAR{gamma}. Taken together, these data suggest that hypoxia and ROS decrease adiponectin production and augment PAI-1 expression in adipocytes via distinct signaling pathways. These effects may contribute to hypoadiponectinemia and elevated PAI-1 levels in obesity, type 2 diabetes, and cardiovascular diseases.

  18. Adiponectin is associated with risk of the metabolic syndrome and insulin resistance in women.

    PubMed

    King, George A; Deemer, Sarah E; Thompson, Dixie L

    2012-12-01

    The purpose of this study was to examine insulin resistance, markers of the metabolic syndrome, cardiovascular disease (CVD) risk, and serum adiponectin concentrations in pre-menopausal Hispanic and non-Hispanic White (NHW) women. This cross-sectional study examined 119 pre-menopausal women (76 Hispanic, 45 NHW) for markers of the metabolic syndrome (ATP III criteria), level of insulin resistance (HOMA-IR), CVD risk factors, and serum total adiponectin concentrations. Relationships between variables were assessed using Student's t-tests, Pearson's and Spearman's Rho correlations, and stepwise multiple regression analysis. Hispanic women had significantly lower adiponectin concentrations than NHW women, even after controlling for body fat (%) (P < 0.01). Number of markers of the metabolic syndrome was inversely related to total adiponectin concentration for all women combined and for NHW women (P ≤ 0.04), but not for Hispanic women. Insulin resistance was inversely related to adiponectin for all women and for NHW women (P < 0.01), but not significantly associated in Hispanic women. Adiponectin concentration was not significantly associated with number of CVD risk factors for these women. While adiponectin was associated with markers of metabolic syndrome and insulin resistance for all women of this study and despite lower adiponectin concentrations for Hispanic women than NHW women, the role of adiponectin to these conditions among Hispanics remains unclear. There was no significant association between adiponectin and CVD risk for these women. Future research should focus on understanding mechanisms for up-regulating adiponectin secretion and if ethnicity affects adiponectin gene expression and secretion given the beneficial effects derived from elevated adiponectin levels.

  19. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway

    SciTech Connect

    Luo Xianghang; Guo Lijuan; Yuan Lingqing; Xie Hui; Zhou Houde; Wu Xianping; Liao Eryuan . E-mail: eyliao1207@21cn.com

    2005-09-10

    Adipocytes can highly and specifically express adiponectin, and the adiponectin receptor (AdipoR) has been detected in bone-forming cells. The present study was undertaken to investigate the action of adiponectin on osteoblast proliferation and differentiation. AdipoR1 protein was detected in human osteoblasts. Adiponectin promoted osteoblast proliferation and resulted in a dose- and time-dependent increase in alkaline phosphatase (ALP) activity, osteocalcin and type I collagen production, and an increase in mineralized matrix. Suppression of AdipoR1 with small-interfering RNA (siRNA) abolished the adiponectin-induced cell proliferation and ALP expression. Adiponectin induces activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal Kinase (JNK), but not ERK1/2 in osteoblasts, and these effects were blocked by suppression of AdipoR1 with siRNA. Furthermore, pretreatment of osteoblasts with the JNK inhibitor SP600125 abolished the adiponectin-induced cell proliferation. p38 inhibitor SB203580 blocked the adiponectin-induced ALP activity. These data indicate that adiponectin induces human osteoblast proliferation and differentiation, and the proliferation response is mediated by the AdipoR/JNK pathway, while the differentiation response is mediated via the AdipoR/p38 pathway. These findings suggest that osteoblasts are the direct targets of adiponectin.

  20. Mitochondrial dysfunction and activation of iNOS are responsible for the palmitate-induced decrease in adiponectin synthesis in 3T3L1 adipocytes

    PubMed Central

    Jeon, Min Jae; Leem, Jaechan; Ko, Myoung Seok; Jang, Jung Eun; Park, Hye-Sun; Kim, Hyun Sik; Kim, Mina; Kim, Eun Hee; Yoo, Hyun Ju; Lee, Chul-Ho; Park, In-Sun; Lee, Ki-Up

    2012-01-01

    Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are considered the key determinants of insulin resistance. Impaired mitochondrial function in obese animals was shown to induce the ER stress response, resulting in reduced adiponectin synthesis in adipocytes. The expression of inducible nitric oxide synthase (iNOS) is increased in adipose tissues in genetic and dietary models of obesity. In this study, we examined whether activation of iNOS is responsible for palmitate-induced mitochondrial dysfunction, ER stress, and decreased adiponectin synthesis in 3T3L1 adipocytes. As expected, palmitate increased the expression levels of iNOS and ER stress response markers, and decreased mitochondrial contents. Treatment with iNOS inhibitor increased adiponectin synthesis and reversed the palmitate-induced ER stress response. However, the iNOS inhibitor did not affect the palmitate-induced decrease in mitochondrial contents. Chemicals that inhibit mitochondrial function increased iNOS expression and the ER stress response, whereas measures that increase mitochondrial biogenesis (rosiglitazone and adenoviral overexpression of nuclear respiratory factor-1) reversed them. Inhibition of mitochondrial biogenesis prevented the rosiglitazone-induced decrease in iNOS expression and increase in adiponectin synthesis. These results suggest that palmitate-induced mitochondrial dysfunction is the primary event that leads to iNOS induction, ER stress, and decreased adiponectin synthesis in cultured adipocytes. PMID:22809900

  1. Fetuin-A downregulates adiponectin through Wnt-PPARγ pathway in lipid induced inflamed adipocyte.

    PubMed

    Agarwal, Soumik; Chattopadhyay, Mrittika; Mukherjee, Sandip; Dasgupta, Suman; Mukhopadhyay, Satinath; Bhattacharya, Samir

    2017-01-01

    Adiponectin secreted from adipocytes is an anti-diabetic and anti-atherogenic adipokine. Adiponectin level is known to fall significantly in obesity induced type 2 diabetes which worsen insulin sensitivity because of aberrant lipid management. However, underlying mechanism of adiponectin decrease in obese diabetic condition is yet unclear. We report here that lowering of plasma adiponectin coincided with the higher Fetuin A (FetA) level in high fat diet (HFD) induced obese diabetic mice. Knock down of FetA gene (FetA(KD)) elevated adiponectin level markedly in HFD mice, while reinforcement of FetA into FetA(KD)HFD mice reduced its level again. These results indicate FetA's involvement in the lowering of adiponectin level in obesity induced diabetic mice. Our findings to understand how FetA could affect adiponectin decrease demonstrated that FetA could enhance Wnt3a expression in the adipocyte of HFD mice. FetA addition to 3T3L1 adipocyte incubation elevated Wnt3a expression in a dose dependent manner. Overexpression of Wnt3a by FetA inhibited PPARγ and adiponectin. FetA failed to reduce PPARγ and adiponectin in Wnt3a gene knocked down 3T3L1` adipocytes. All these suggest that FetA mediate its inhibitory effect on adiponectin through Wnt3a-PPARγ pathway. Inhibition of adiponectin expression through FetA and Wnt3a significantly compromised with the activation of AMPK and its downstream signalling molecules which adversely affected lipid management causing loss of insulin sensitivity. Downregulation of adiponectin in inflamed adipocyte by FetA through the mediation of Wnt3a and PPARγ is a new report.

  2. Adiponectin pathway polymorphisms and risk of breast cancer in African Americans and Hispanics in the Women's Health Initiative.

    PubMed

    Kaklamani, Virginia G; Hoffmann, Thomas J; Thornton, Timothy A; Hayes, Geoffrey; Chlebowski, Rowan; Van Horn, Linda; Mantzoros, Christos

    2013-06-01

    Adiponectin, a protein secreted by the adipose tissue, is an endogenous insulin sensitizer with circulating levels that are decreased in obese and diabetic subjects. Recently, circulating levels of adiponectin have been correlated with breast cancer risk. Our previous work showed that polymorphisms of the adiponectin pathway are associated with breast cancer risk. We conducted the first study of adiponectin pathways in African Americans and Hispanics in the Women's Health Initiative SNP Health Association Resource cohort of 3,642 self-identified Hispanic women and 8,515 self-identified African American women who provided consent for DNA analysis. Single nucleotide polymorphisms (SNPs) from three genes were included in this analysis: ADIPOQ, ADIPOR1, and ADIPOR2. The genome-wide human SNP array 6.0 (909,622 SNPs) ( www.affymetrix.com ) was used. We found that rs1501299, a functional SNP of ADIPOQ that we previously reported was associated with breast cancer risk in a mostly Caucasian population, was also significantly associated with breast cancer incidence (HR for the GG/TG genotype: 1.23; 95 % CI 1.059-1.43) in African American women. We did not find any other SNPs in these genes to be associated with breast cancer incidence. This is the first study assessing the role of adiponectin pathway SNPs in breast cancer risk in African Americans and Hispanics. RS1501299 is significantly associated with breast cancer risk in African American women. As the rates of obesity and diabetes increase in African Americans and Hispanics, adiponectin and its functional SNPs may aid in breast cancer risk assessment.

  3. Angiotensin-converting enzyme (ACE) inhibitors modulate cellular retinol-binding protein 1 and adiponectin expression in adipocytes via the ACE-dependent signaling cascade.

    PubMed

    Kohlstedt, Karin; Gershome, Cynthia; Trouvain, Caroline; Hofmann, Wolf-Karsten; Fichtlscherer, Stephan; Fleming, Ingrid

    2009-03-01

    Inhibitors of the angiotensin-converting enzyme (ACE) decrease angiotensin II production and activate an intracellular signaling cascade that affects gene expression in endothelial cells. Because ACE inhibitors have been reported to delay the onset of type 2 diabetes, we determined ACE signaling-modulated gene expression in endothelial cells and adipocytes. Using differential gene expression analysis, several genes were identified that were 3-fold up- or down-regulated by ramiprilat in cells expressing wild-type ACE versus cells expressing a signaling-dead ACE mutant. One up-regulated gene was the cellular retinol-binding protein 1 (CRBP1). In adipocytes, the overexpression of CRBP1 enhanced (4- to 5-fold) the activity of promoters containing response elements for retinol-dependent nuclear receptors [retinoic acid receptor (RAR) and retinoid X receptor (RXR)] or peroxisome proliferator-activated receptors (PPAR). CRBP1 overexpression also enhanced the promoter activity (by 470 +/- 40%) and expression/release of the anti-inflammatory and antiatherogenic adipokine adiponectin (cellular adiponectin by 196 +/- 24%, soluble adiponectin by 228 +/- 74%). Significantly increased adiponectin secretion was also observed after ACE inhibitor treatment of human preadipocytes, an effect prevented by small interfering RNA against CRBP1. Furthermore, in ob/ob mice, ramipril markedly potentiated both the basal (approximately 2-fold) and rosiglitazonestimulated circulating levels of adiponectin. In patients with coronary artery disease or type 2 diabetes, ACE inhibition also significantly increased plasma adiponectin levels (1.6- or 2.1-fold, respectively). In summary, ACE inhibitors affect adipocyte homeostasis via CRBP1 through the activation of RAR/RXR-PPAR signaling and up-regulation of adiponectin. The latter may contribute to the beneficial effects of ACE inhibitors on the development of type 2 diabetes in patients with an activated renin-angiotensin system.

  4. Associations of adiponectin and fertility estimates in Holstein bulls.

    PubMed

    Kasimanickam, Vanmathy R; Kasimanickam, Ramanathan K; Kastelic, John P; Stevenson, Jeffrey S

    2013-03-15

    Adiponectin is a pleiotropic regulator of numerous biological functions, including gonadal steroidogenesis and might play a role in sperm structures and functions. The objectives were to: (1) determine associations among serum concentrations of adiponectin, testosterone, and prolactin, and the sperm DNA fragmentation index; (2) associate sperm adiponectin mRNA abundance with estimates of fertility (sire conception rate); and (3) determine sperm protein expression of adiponectin and its receptor in pre- and postcapacitated sperm from Holstein bulls. In experiment 1, biweekly serum concentrations of adiponectin, prolactin, and testosterone were greater (P < 0.05) for high fertility bulls compared with average and low fertility bulls. Furthermore, sperm DNA fragmentation index was greater (P < 0.05) for low fertility compared with both average and high fertility bulls. In experiment 2, samples of sperm from a single collection from commercial Holstein bulls (N = 34) were used to evaluate relative sperm mRNA expression of adiponectin and its receptors, AdipoR1 and AdipoR2, and protein levels of adiponectin and its receptors, AdipoR1 and AdipoR2, in pre- and postcapacitation sperm. The mRNA abundance of adiponectin and its receptors, AdipoR1 and AdipoR2, were greater for high fertility bulls (>2 to ≤4 sire conception rate) compared with average (≥2 to ≤2) and low (>-2 to ≤-4) fertility bulls. Based on the sperm capacitation assay, average fertility bulls had a greater percentage of acrosome-reacted sperm at 5 hours than high and low fertility bulls, whereas high fertility bulls had a greater percentage of acrosome-reacted sperm than low fertility bulls. After capacitation, levels of adiponectin protein were lower in average fertility bulls, AdipoR1 was lower in all fertility groups, and AdipoR2 was lower in average and high fertility bulls. In conclusion, adiponectin and its receptors had vital roles in sperm structural and functional traits and consequently

  5. Inside out: Bone marrow adipose tissue as a source of circulating adiponectin

    PubMed Central

    Scheller, Erica L.; Burr, Aaron A.; MacDougald, Ormond A.; Cawthorn, William P.

    2016-01-01

    ABSTRACT The adipocyte-derived hormone adiponectin mediates beneficial cardiometabolic effects, and hypoadiponectinemia is a biomarker for increased metabolic and cardiovascular risk. Indeed, circulating adiponectin decreases in obesity and insulin-resistance, likely because of impaired production from white adipose tissue (WAT). Conversely, lean states such as caloric restriction (CR) are characterized by hyperadiponectinemia, even without increased adiponectin production from WAT. The reasons underlying this paradox have remained elusive, but our recent research suggests that CR-associated hyperadiponectinemia derives from an unexpected source: bone marrow adipose tissue (MAT). Herein, we elaborate on this surprising discovery, including further discussion of potential mechanisms influencing adiponectin production from MAT; additional evidence both for and against our conclusions; and observations suggesting that the relationship between MAT and adiponectin might extend beyond CR. While many questions remain, the burgeoning study of MAT promises to reveal further key insights into MAT biology, both as a source of adiponectin and beyond. PMID:27617171

  6. Unique profile of chicken adiponectin, a predominantly heavy molecular weight multimer, and relationship to visceral adiposity.

    PubMed

    Hendricks, Gilbert L; Hadley, Jill A; Krzysik-Walker, Susan M; Prabhu, K Sandeep; Vasilatos-Younken, Regina; Ramachandran, Ramesh

    2009-07-01

    Adiponectin, a 30-kDa adipokine hormone, circulates as heavy, medium, and light molecular weight isoforms in mammals. Plasma heavy molecular weight (HMW) adiponectin isoform levels are inversely correlated with the incidence of type 2 diabetes in humans. The objectives of the present study were to characterize adiponectin protein and quantify plasma adiponectin levels in chickens, which are naturally hyperglycemic relative to mammals. Using gel filtration column chromatography and Western blot analysis under nonreducing and non-heat-denaturing native conditions, adiponectin in chicken plasma, and adipose tissue is predominantly a multimeric HMW isoform that is larger than 669 kDa mass. Under reducing conditions and heating to 70-100 C, however, a majority of the multimeric adiponectin in chicken plasma and adipose tissue was reduced to oligomeric and/or monomeric forms. Immunoprecipitation and elution under neutral pH preserved the HMW adiponectin multimer, whereas brief exposure to acidic pH led to dissociation of HMW multimer into multiple oligomers. Mass spectrometric analysis of chicken adiponectin revealed the presence of hydroxyproline and differential glycosylation of hydroxylysine residues in the collagenous domain. An enzyme immunoassay was developed and validated for quantifying plasma adiponectin in chickens. Plasma adiponectin levels were found to be significantly lower in 8- compared with 4-wk-old male chickens and inversely related to abdominal fat pad mass. Collectively, our results provide novel evidence that adiponectin in chicken plasma and tissues is predominantly a HMW multimer, suggesting the presence of unique multimerization and stabilization mechanisms in the chicken that favors preponderance of HMW adiponectin over other oligomers.

  7. Effect of Probiotic Soy Milk on Serum Levels of Adiponectin, Inflammatory Mediators, Lipid Profile, and Fasting Blood Glucose Among Patients with Type II Diabetes Mellitus.

    PubMed

    Feizollahzadeh, Sadegh; Ghiasvand, Reza; Rezaei, Abbas; Khanahmad, Hossein; Sadeghi, Akram; Hariri, Mitra

    2017-03-01

    Probiotic therapies are going to be an effective alternative therapeutic strategy in the treatment and management of diabetes. The mechanism behind the essential effects of probiotic therapies in diabetic patients was not fully understood. The objective of this study was to evaluate the effects of probiotic soy milk containing Lactobacillus planetarum A7 on inflammation, lipid profile, fasting blood glucose, and serum adiponectin among patients with type 2 diabetes mellitus. Forty patients with type 2 diabetes, at the age of 35-68 years old, were assigned to two groups in this randomized, double-blind, controlled clinical trial. The patients in the intervention group consumed 200 ml/day of probiotic soy milk containing L. planetarum A7 and those in control group consumed 200 ml/day of pure soy milk for 8 weeks. Serum TNF-α, C reactive protein, adiponectin, lipid profile, and fasting blood glucose were determined before and after intervention. In intervention group, serum adiponectin in pre- and post-treatment did not show any significant changes (2.52 ± 0.74 vs 2.84 ± 0.61, P = 0.658), as well as changes in serum TNF-α and C reactive protein (172.44 ± 5.7 vs 172.83 ± 7.6, P = 0.278, 4.2 ± 1.4 vs 4.5 ± 1.9, P = 0.765, respectively). Low-density cholesterol and high-density cholesterol changed significantly (P = 0.023, P = 0.017, respectively), but fasting blood glucose did not show any significant changes. The results of this study showed that consumption of probiotic soy milk and soy milk has no effect on serum adiponectin and inflammation, but it can change lipid profile among type 2 diabetic patients.

  8. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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:...

  10. 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.

  11. Evolving role of adiponectin in cancer-controversies and update

    PubMed Central

    Katira, Arnav; Tan, Peng H.

    2016-01-01

    Adiponectin (APN), an adipokine produced by adipocytes, has been shown to have a critical role in the pathogenesis of obesity-associated malignancies. Through its receptor interactions, APN may exert its anti-carcinogenic effects including regulating cell survival, apoptosis and metastasis via a plethora of signalling pathways. Despite the strong evidence supporting this notion, some work may indicate otherwise. Our review addresses all controversies critically. On the whole, hypoadiponectinaemia is associated with increased risk of several malignancies and poor prognosis. In addition, various genetic polymorphisms may predispose individuals to increased risk of obesity-associated malignancies. We also provide an updated summary on therapeutic interventions to increase APN levels that are of key interest in this field. To date efforts to manipulate APN levels have been promising, but much work remains to be done. PMID:27144066

  12. Molecular mechanisms of diabetes and atherosclerosis: role of adiponectin.

    PubMed

    Kishida, Ken; Funahashi, Tohru; Shimomura, Iichiro

    2012-06-01

    Type 2 diabetes mellitus (T2DM) is a disease characterized by inadequate beta-cell response due to progressive insulin resistance that typically accompanies physical inactivity and weight gain. T2DM is associated with substantial morbidity and mortality related to the associated atherosclerotic cardiovascular risks and diabetic vasculopathies, including microangiopathies (e.g., blindness and renal failure) and macroangiopathies (atherosclerosis). The increasing global prevalence of T2DM is linked to the rising rates of obesity, especially abdominal obesity. Visceral fat accumulation is upstream of obesity-related disorders including atherosclerotic cardiovascular disease (ACVD), and is associated with impaired insulin sensitivity and atherosclerosis through dysregulated production of adipocytokines, especially hypoadiponectinemia. This review article discusses the pathophysiological mechanisms responsible for T2DM and atherosclerosis, focusing on adiponectin. Clinical and experimental studies have shown that hypoadiponectinemia contributes to a variety of life style-related diseases including T2DM and atherosclerosis. It is likely that life-style modification, visceral fat reduction and use of medications that increase serum adiponectin levels (e.g., rimonabant, thiazolidinediones, fibrates, angiotensin receptor blocker and mineralocorticoid receptor blockade) when provided in combination can improve hypoadiponectinemia and thus prevent the development of life style-related diseases including T2DM and ACVD.

  13. Methanolic leaf extract of Gymnema sylvestre augments glucose uptake and ameliorates insulin resistance by upregulating glucose transporter-4, peroxisome proliferator-activated receptor-gamma, adiponectin, and leptin levels in vitro

    PubMed Central

    Kumar, Puttanarasaiah Mahesh; Venkataranganna, Marikunte V.; Manjunath, Kirangadur; Viswanatha, Gollapalle L.; Ashok, Godavarthi

    2016-01-01

    Aims: The present study was undertaken to evaluate the effect of methanolic leaf extract of Gymnema sylvestre (MLGS) on glucose transport (GLUT) and insulin resistance in vitro. Materials and Methods: Peroxisome proliferator-activated receptor-gamma (PPAR-γ) and GLUT-4 expression were assessed in L6 myotubes for concluding the GLUT activity, and adiponectin and leptin expression was studied in 3T3 L1 murine adipocyte cell line to determine the effect of MLGS (250-750 μg/ml) on insulin resistance. Results: The findings of the experiments have demonstrated a significant and dose-dependent increase in glucose uptake in all the tested concentrations of MLGS, further the glucose uptake activity of MLGS (750 μg/ml) was at par with rosiglitazone (50 μg/ml). Concomitantly, MLGS has shown enhanced GLUT-4 and PPAR-γ gene expressions in L6 myotubes. Furthermore, cycloheximide (CHX) had completely abolished the glucose uptake activity of MLGS when co-incubated, which further confirmed that glucose uptake activity of MLGS was linked to enhanced expression of GLUT-4 and PPAR-γ. In addition, in another experimental set, MLGS showed enhanced expression of adiponectin and leptin, thus confirms the ameliorative effect of MLGS on insulin resistance. Conclusion: These findings suggest that MLGS has an enhanced glucose uptake activity in L6 myotubes, and ameliorate the insulin resistance in 3T3 L1 murine adipocyte cell line in vitro. PMID:27104035

  14. Serum Adiponectin, C-peptide and Leptin and Risk of Symptomatic Benign Prostatic Hyperplasia: Results From the Prostate Cancer Prevention Trial

    PubMed Central

    Schenk, Jeannette M.; Kristal, Alan R.; Neuhouser, Marian L.; Tangen, Catherine M.; White, Emily; Lin, Daniel W.; Thompson, Ian M.

    2010-01-01

    Background Recent epidemiologic studies have identified obesity as a risk factor for benign prostatic hyperplasia (BPH). We examined whether adiponectin, leptin and C-peptide were associated with incident, symptomatic BPH and whether these factors mediate the relationship between obesity and BPH risk. Methods Data are from Prostate Cancer Prevention Trial placebo arm participants who were free of BPH at baseline. Incident BPH (n=698) was defined as treatment, two International Prostate Symptom Score (IPSS) values >14, or an increase of ≥5 in IPSS from baseline documented on at least two occasions plus at least one score ≥12. Controls (n=709) were selected from men reporting no BPH treatment or IPSS >7 during the seven-year trial. Baseline serum was analyzed for adiponectin, C-peptide, and leptin concentrations. Results Neither C-peptide nor leptin was associated with BPH risk. The odds ratio [95% CI] contrasting highest to lowest quartiles of adiponectin was 0.65[0.47, 0.87] ptrend=0.004. Findings differed between levels of physical activity: there was a strong inverse association between adiponectin and BPH among moderately/very active men OR=0.43[0.29, 0.63], and no association among sedentary/minimally active men OR=0.92[0.65, 1.30] pinteraction=0.005. Adiponectin concentrations explained only a moderate amount of the relationship between obesity and BPH risk. Conclusions High adiponectin concentrations were associated with reduced risk of incident, symptomatic BPH. This association was limited to moderately/very active men; suggesting the relationship between obesity and BPH involves a complex interaction between factors affecting glucose uptake and insulin sensitivity. However, adiponectin is likely not the only mechanism through which obesity affects BPH risk. PMID:19475640

  15. Effect of L-arginine supplementation on insulin resistance and serum adiponectin concentration in rats with fat diet

    PubMed Central

    Miczke, Anna; Suliburska, Joanna; Pupek-Musialik, Danuta; Ostrowska, Lucyna; Jabłecka, Anna; Krejpcio, Zbigniew; Skrypnik, Damian; Bogdański, Paweł

    2015-01-01

    Object: The purpose of this study was to determine whether supplementation with L-arginine, a substrate used in the production of nitric oxide, had an effect on adiponectin concentration in rats fed a high-fat diet. The influence of L-arginine on insulin resistance was also evaluated. Materials and methods: The experiment was performed using 36 Wistar rats divided into three groups: group 1 was fed a standard diet, group 2 a high-fat (HF) diet, group 3 a HF diet supplemented with L-arginine. After 42 days, serum levels of lipids, glucose, insulin, NO, and adiponectin were measured. Insulin resistance (IR) was estimated by the Homeostasis Model Assessment (HOMA). Results: Body mass was equal in all 3 groups, at the beginning as well as at the end of the study, however, in group 2 the amount of visceral fat was greater after 42 days. In group 3, there was a tendency for visceral fat to decrease. An increase in cholesterol, triglycerides, insulin and HOMA-IR, as well as a decrease in NO and adiponectin were seen in group 2, while in group 3, L-arginine supplementation ameliorated these disturbances. Conclusions: Our study shows that L-arginine supplementation in rats fed a HF diet is associated with an increase in insulin sensitivity. Our findings suggest that the underlying mechanism could be at least partially related to an increase in adiponectin concentration. PMID:26379826

  16. Insulin, leptin, and adiponectin receptors in colon: regulation relative to differing body adiposity independent of diet and in response to dimethylhydrazine.

    PubMed

    Drew, Janice E; Farquharson, Andrew J; Padidar, Sara; Duthie, Garry G; Mercer, Julian G; Arthur, John R; Morrice, Philip C; Barrera, Lawrence N

    2007-10-01

    Obesity has recently become a focus of research to elucidate diet and lifestyle factors as important risk factors for colon cancer. Altered levels of insulin, leptin, and adiponectin have been identified as potential candidates increasing colon cancer risk within the prevailing obesogenic environment. There has been considerable research to characterize signaling via these hormones in the brain, liver, and adipose tissue; however, very little is known of their emerging role in peripheral signaling, particularly in epithelial tissues. This study profiles insulin, leptin, and adipokine receptors in the rat colon, revealing novel microanatomical location of these receptors and thereby supporting a potential role in regulating colonic tissue. Potential involvement of insulin, leptin, and adiponectin receptors in increased risk of colon cancer was investigated using Sprague-Dawley rats, either resistant or susceptible to diet-induced obesity. Regulation of insulin, leptin, and adiponectin receptors as a consequence of differing levels of adiposity was assessed regionally in the colon in response to treatment with the chemical carcinogen 1,2-dimethylhydrazine (DMH). However, significantly increased fat mass, increased levels of plasma insulin, leptin, and triglycerides, previously associated with an increased risk of colon cancer, were not associated with promotion of precancerous lesions in the experimental rats or deregulation of insulin, leptin, or adiponectin receptors. These findings do not support a direct link between the deregulation of insulin and adipokine levels observed in obese rats and an increased risk of colon carcinogenesis.

  17. Adiponectin modulates excitability of rat paraventricular nucleus neurons by differential modulation of potassium currents.

    PubMed

    Hoyda, Ted D; Ferguson, Alastair V

    2010-07-01

    The adipocyte-derived hormone adiponectin acts at two seven-transmembrane domain receptors, adiponectin receptor 1 and adiponectin receptor 2, present in the paraventricular nucleus of the hypothalamus to regulate neuronal excitability and endocrine function. Adiponectin depolarizes rat parvocellular preautonomic neurons that secrete either thyrotropin releasing hormone or oxytocin and parvocellular neuroendocrine corticotropin releasing hormone neurons, leading to an increase in plasma adrenocorticotropin hormone concentrations while also hyperpolarizing a subgroup of neurons. In the present study, we investigate the ionic mechanisms responsible for these changes in excitability in parvocellular paraventricular nucleus neurons. Patch clamp recordings of currents elicited from slow voltage ramps and voltage steps indicate that adiponectin inhibits noninactivating delayed rectifier potassium current (I(K)) in a majority of neurons. This inhibition produced a broadening of the action potential in cells that depolarized in the presence of adiponectin. The depolarizing effects of adiponectin were abolished in cells pretreated with tetraethyl ammonium (0/15 cells depolarize). Slow voltage ramps performed during adiponectin-induced hyperpolarization indicate the activation of voltage-independent potassium current. These hyperpolarizing responses were abolished in the presence of glibenclamide [an ATP-sensitive potassium (K(ATP)) channel blocker] (0/12 cells hyperpolarize). The results presented in this study suggest that adiponectin controls neuronal excitability through the modulation of different potassium conductances, effects which contribute to changes in excitability and action potential profiles responsible for peptidergic release into the circulation.

  18. Adiponectin deficiency promotes tumor growth in mice by reducing macrophage infiltration.

    PubMed

    Sun, Yutong; Lodish, Harvey F

    2010-08-05

    Adiponectin is an adipocyte-derived plasma protein that has been implicated in regulating angiogenesis, but the role of adiponectin in regulating this process is still controversial. In this study, in order to determine whether adiponectin affects tumor growth and tumor induced vascularization, we implanted B16F10 melanoma and Lewis Lung Carcinoma cells subcutaneously into adiponectin knockout and wild-type control mice, and found that adiponectin deficiency markedly promoted the growth of both tumors. Immunohistochemical analyses indicated that adiponectin deficiency reduced macrophage recruitment to the tumor, but did not affect cancer cell mitosis, apoptosis, or tumor-associated angiogenesis. In addition, treatment with recombinant adiponectin did not affect the proliferation of cultured B16F10 tumor cells. Importantly, the restoration of microphage infiltration at an early stage of tumorigenesis by means of co-injection of B16F10 cells and macrophages reversed the increased tumor growth in adiponectin knockout mice. Thus, we conclude that the enhanced tumor growth observed in adiponectin deficient mice is likely due to the reduction of macrophage infiltration rather than enhanced angiogenesis.

  19. Crystal structures of the human adiponectin receptors

    PubMed Central

    Tanabe, Hiroaki; Fujii, Yoshifumi; Hosaka, Toshiaki; Motoyama, Kanna; Ikeda, Mariko; Wakiyama, Motoaki; Terada, Takaho; Ohsawa, Noboru; Hato, Masakatsu; Ogasawara, Satoshi; Hino, Tomoya; Murata, Takeshi; Iwata, So; Hirata, Kunio; Kawano, Yoshiaki; Yamamoto, Masaki; Kimura-Someya, Tomomi; Shirouzu, Mikako; Yamauchi, Toshimasa; Kadowaki, Takashi; Yokoyama, Shigeyuki

    2015-01-01

    Adiponectin stimulation of its receptors, AdipoR1 and AdipoR2, increases AMPK and PPAR activities, respectively, thereby contributing to healthy longevity as key anti-diabetic molecules. AdipoR1 and AdipoR2 were predicted to contain seven transmembrane helices with the opposite topology to G protein-coupled receptor (GPCR)s. Here we report the crystal structures of human AdipoR1 and AdipoR2 at 2.9- and 2.4-Å resolution, respectively, which represent a novel class of receptor structure. The seven-transmembrane helices, conformationally distinct from those of GPCRs, enclose a large cavity where three conserved histidine residues coordinate a zinc ion. The zinc-binding structure may play a role in the adiponectin-stimulated AMPK phosphorylation and UCP2 upregulation. Adiponectin may broadly interact with the extracellular face, rather than the C-terminal flexible tail, of the receptors. The present information will facilitate the understanding of novel structure-function relationships and the development and optimization of AdipoR agonists for the treatment of obesity-related diseases, such as type 2 diabetes. PMID:25855295

  20. Perinatal BPA exposure induces hyperglycemia, oxidative stress and decreased adiponectin production in later life of male rat offspring.

    PubMed

    Song, Shunzhe; Zhang, Ling; Zhang, Hongyuan; Wei, Wei; Jia, Lihong

    2014-04-03

    The main object of the present study was to explore the effect of perinatal bisphenol A (BPA) exposure on glucose metabolism in early and later life of male rat offspring, and to establish the potential mechanism of BPA-induced dysglycemia. Pregnant rats were treated with either vehicle or BPA by drinking water at concentrations of 1 and 10 µg/mL BPA from gestation day 6 through the end of lactation. We measured the levels of fasting serum glucose, insulin, adiponectin and parameters of oxidative stress on postnatal day (PND) 50 and PND100 in male offspring, and adiponectin mRNA and protein expression in adipose tissue were also examined. Our results showed that perinatal exposure to 1 or 10 µg/mL BPA induced hyperglycemia with insulin resistance on PND100, but only 10 µg/mL BPA exposure had similar effects as early as PND50. In addition, increased oxidative stress and decreased adiponectin production were also observed in BPA exposed male offspring. Our findings indicated that perinatal exposure to BPA resulted in abnormal glucose metabolism in later life of male offspring, with an earlier and more exacerbated effect at higher doses. Down-regulated expression of adiponectin gene and increased oxidative stress induced by BPA may be associated with insulin resistance.

  1. 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.

  2. 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

  3. Adiponectin expression is decreased in the involved skin and sera of diffuse cutaneous scleroderma patients.

    PubMed

    Arakawa, Hiroki; Jinnin, Masatoshi; Muchemwa, Faith C; Makino, Takamitsu; Kajihara, Ikko; Makino, Katsunari; Honda, Noritoshi; Sakai, Keisuke; Fukushima, Satoshi; Ihn, Hironobu

    2011-09-01

    In this study, we determined the adiponectin expression in the serum and lesional skin of patients with scleroderma (SSc). Serum adiponectin concentrations were measured in 32 patients with SSc, 10 patients with SLE, 12 patients with dermatomyositis patients and 13 healthy subjects with specific enzyme-linked immunosorbent assays. Adiponectin mRNA was determined in skin tissues of five patients with diffuse cutaneous SSc (dcSSc), seven patients with limited cutaneous SSc (lcSSc) and seven healthy subjects with real-time polymerase chain reaction. There was a significant reduction in serum adiponectin levels in patients with dcSSc. SSc patients with decreased serum adiponectin levels had higher total skin thickness score and higher incidence of pulmonary fibrosis. Adiponectin mRNA levels in skin tissues from patients with dcSSc were also reduced. Serum adiponectin levels may be a useful biomarker for fibrotic condition in patients with SSc. Clarifying the role of adiponectin in collagen diseases may lead to further understanding of the pathogenesis and new therapeutic approach.

  4. Expression of adiponectin and adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) in the porcine uterus during the oestrous cycle.

    PubMed

    Smolinska, Nina; Dobrzyn, Kamil; Maleszka, Anna; Kiezun, Marta; Szeszko, Karol; Kaminski, Tadeusz

    2014-04-01

    Adiponectin is a hormone secreted primarily by white adipose tissue. Recent studies have shown that adiponectin and its receptors (AdipoR1 and AdipoR2) are expressed in different reproductive tissues, including the ovary and uterus. This newly discovered endocrine system plays an important role in the regulation of reproductive processes. The expression of the adiponectin system in the porcine uterus during the oestrous cycle has not been researched to date. The aim of the present study was to investigate the presence and changes in adiponectin system expression in the porcine uterus on days 2-3, 10-12, 14-16, and 17-19 of the oestrous cycle. The expression of the adiponectin gene was highest on days 14-16 and 2-3 in the endometrium and myometrium, respectively. In the endometrium, the content of AdipoR1 and AdipoR2 mRNAs was highest on days 10-12, whereas significantly higher expression levels of both genes were noted in the myometrium on days 17-19. The highest content of adiponectin and AdipoR1 protein in the endometrium was reported on days 2-3. In the myometrium, the expression levels of both receptor proteins were significantly higher on days 17-19. Adiponectin system proteins were localized in endometrial epithelial glandular cells, luminal epithelial cells and stromal cells as well as in longitudinal and circular muscles of the myometrium. This study demonstrated the presence of adiponectin, AdipoR1 and AdipoR2 genes and proteins in the porcine uterus and the effect of the stage of the oestrous cycle on the expression of the adiponectin system. Our results suggest that locally synthesized adiponectin directly affects uterine functions.

  5. Effect of Drinking on Adiponectin in Healthy Men and Women

    PubMed Central

    Imhof, Armin; Plamper, Ines; Maier, Steffen; Trischler, Gerlinde; Koenig, Wolfgang

    2009-01-01

    OBJECTIVE Moderate alcohol consumption is associated with reduced incidence of type 2 diabetes and cardiovascular mortality and increases adiponectin concentrations, but effects might differ according to sex and beverage consumed. RESEARCH DESIGN AND METHODS A total of 72 healthy individuals (22–56 years) were enrolled in this randomized controlled crossover trial. After washout, two interventions for 3 weeks followed: ethanol (concentration 12.5%), beer (5.6%), or red wine (12.5%) equivalent to 30 g ethanol/day for men and 20 g/day for women or the same de-alcoholized beverages or water. Adiponectin was measured by sandwich enzyme-linked immunosorbent assay. RESULTS Among women, adiponectin significantly increased after consuming red wine (29.8%, P < 0.05) and increased among men after ethanol solution (17.4%, P < 0.05) and consuming beer (16.1%, P < 0.05). De-alcoholized beverages had no substantial effect on adiponectin concentrations. CONCLUSIONS Moderate amounts of ethanol-containing beverages increased adiponectin concentrations, but sex-specific effects might depend on type of beverage consumed. PMID:19244090

  6. The Effect of Leptin and Adiponectin on KiSS-1 and KissR mRNA Expression in Rat Islets of Langerhans and CRI-D2 Cell Line

    PubMed Central

    Mahmoodzadeh Sagheb, Mandana; Azarpira, Negar; Yaghobi, Ramin

    2014-01-01

    Background: Leptin and adiponectin are the two key metabolic hormones secreted from adipocytes to control food intake and energy expenditure. The action of both hormones in regulation of Gonadotropin Releasing Hormone (GnRH) secretion from the hypothalamus is mediated through Kisspeptins. Kisspeptins are products of KiSS-1 gene. Leptin and adiponectin are modulators of KiSS-1 expression in the hypothalamus. These peptides have also important roles in pancreatic β-cells to control insulin synthesis and secretion and their receptors are detected in Langerhans islets. We hypothesized that leptin and adiponectin might alter KiSS-1 and Kiss Receptor mRNA expression in the islets. Objectives: The aim of this study is to investigate any modulatory effect that leptin and adiponectin may have on the expression of Kiss-1 and KiSSR gene in Langerhans islets. Materials and Methods: We isolated the islets from adult male rats by collagenase and cultured CRI-D2 cell lines to investigate the effect of leptin and adiponectin. Then, we incubated them with different concentrations of leptin and adiponectin for 24 hours. After that, RNA was extracted from the islets and CRI-D2 cells and transcripted to cDNA. KiSS-1 and KissR expression levels were evaluated by real time PCR. Results: In islet and CRI-D2 cells, leptin increased the KiSS-1 mRNA expression significantly, but adiponectin decreased it was expected. Conclusions: These findings indicated the possibility that KiSS-1 mRNA expression is a mediator of leptin and adiponectin function in the islets. PMID:24910643

  7. Protective role of adiponectin in a rat model of intestinal ischemia reperfusion injury

    PubMed Central

    Liu, Xu-Hui; Yang, Yue-Wu; Dai, Hai-Tao; Cai, Song-Wang; Chen, Rui-Han; Ye, Zhi-Qiang

    2015-01-01

    AIM: To determine the potential protective role of adiponectin in intestinal ischemia reperfusion (I/R) injury. METHODS: A rat model of intestinal I/R injury was established. The serum level of adiponectin in rats with intestinal I/R injury was determined by enzyme-linked immunosorbent assay (ELISA). The serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were also measured by ELISA. Apoptosis of intestinal cells was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The production of malondialdehyde (MDA) and superoxide dismutase (SOD) and villous injury scores were also measured. RESULTS: Adiponectin was downregulated in the serum of rats with intestinal I/R injury compared with sham rats. No significant changes in the expression of adiponectin receptor 1 and adiponectin receptor 2 were found between sham and I/R rats. Pre-treatment with recombinant adiponectin attenuated intestinal I/R injury. The production of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, in rats with intestinal I/R injury was reduced by adiponectin pre-treatment. The production of MDA was inhibited, and the release of SOD was restored by adiponectin pre-treatment in rats with intestinal I/R injury. Adiponectin pre-treatment also inhibited cell apoptosis in these rats. Treatment with the AMP-activated protein kinase (AMPK) signaling pathway inhibitor, compound C, or the heme oxygenase 1 (HO-1) inhibitor, Snpp, attenuated the protective effects of adiponectin against intestinal I/R injury. CONCLUSION: Adiponectin exhibits protective effects against intestinal I/R injury, which may involve the AMPK/HO-1 pathway. PMID:26715807

  8. Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin.

    PubMed

    Yau, Suk Yu; Li, Ang; Hoo, Ruby L C; Ching, Yick Pang; Christie, Brian R; Lee, Tatia M C; Xu, Aimin; So, Kwok-Fai

    2014-11-04

    Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood-brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression.

  9. Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin

    PubMed Central

    Yau, Suk Yu; Li, Ang; Hoo, Ruby L. C.; Ching, Yick Pang; Christie, Brian R.; Lee, Tatia M. C.; Xu, Aimin; So, Kwok-Fai

    2014-01-01

    Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood–brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression. PMID:25331877

  10. 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

  11. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26703682

  13. Role of Adiponectin and Its Receptors in Cancer

    PubMed Central

    Obeid, Stephanie; Hebbard, Lionel

    2012-01-01

    Adiponectin (APN), a novel hormone/cytokine derived from adipocyte tissue, is involved in various physiological functions. Genetics, nutrition, and adiposity are factors contributing to circulating plasma concentrations of APN. Clinical correlation studies have shown that lower levels of serum APN are associated with increased malignancy of various cancers, such as breast and colon cancers, suggesting that APN has a role in tumorigenesis. APN affects insulin resistance, thus further influencing cancer development. Tumor cells may express receptors for APN. Cellular signaling is the mechanism by which APN exerts its host-protective responses. These factors suggest that serum APN levels and downstream signaling targets of APN may serve as potential diagnostic markers for malignancies. Further research is necessary to clarify the exact role of APN in cancer diagnosis and therapy. PMID:23691481

  14. Globular adiponectin enhances invasion in human breast cancer cells

    PubMed Central

    FALK LIBBY, EMILY; LIU, JIANZHONG; LI, YI; LEWIS, MONICA J.; DEMARK-WAHNEFRIED, WENDY; HURST, DOUGLAS R.

    2016-01-01

    Every year, a large number of women succumb to metastatic breast cancer due to a lack of curative approaches for this disease. Adiponectin (AdipoQ) is the most abundant of the adipocyte-secreted adipokines. In recent years, there has been an interest in the use of AdipoQ and AdipoQ receptor agonists as therapeutic agents for the treatment of breast cancer. However, while multiple epidemiological studies have previously indicated that low levels of circulating plasma AdipoQ portend poor prognosis in patients with breast cancer, recent studies have reported that elevated expression levels of AdipoQ in breast tissue are correlated with advanced stages of the disease. Thus, the aim of the present study was to clarify the mechanism by which AdipoQ in breast tissue acts directly on tumor cells to regulate the early steps of breast cancer metastasis. In the present study, the effects of different AdipoQ isoforms on the metastatic potential of human breast cancer cells were investigated. The results revealed that globular adiponectin (gAd) promoted invasive cell morphology and significantly increased the migration and invasion abilities of breast cancer cells, whereas full-length adiponectin (fAd) had no effect on these cells. Additionally, gAd, but not fAd, increased the expression levels of microtubule-associated protein 1 light chain 3 beta (LC3B)-II and intracellular LC3B puncta, which are indicators of autophagosome formation, thus suggesting autophagic induction by gAd. Furthermore, the inhibition of autophagic function by autophagy-related protein 7 knockdown attenuated the gAd-induced increase in invasiveness in breast cancer cells. Therefore, the results of the present study suggested that a specific AdipoQ isoform may enhance breast cancer invasion, possibly via autophagic induction. Understanding the roles of the different AdipoQ isoforms as microenvironmental regulatory molecules may aid the development of effective AdipoQ-based treatments for breast cancer

  15. Adiponectin Induces Oncostatin M Expression in Osteoblasts through the PI3K/Akt Signaling Pathway

    PubMed Central

    Su, Chen-Ming; Lee, Wei-Lin; Hsu, Chin-Jung; Lu, Ting-Ting; Wang, Li-Hong; Xu, Guo-Hong; Tang, Chih-Hsin

    2015-01-01

    Rheumatoid arthritis (RA), a common autoimmune disorder, is associated with a chronic inflammatory response and unbalanced bone metabolism within the articular microenvironment. Adiponectin, an adipokine secreted by adipocytes, is involved in multiple functions, including lipid metabolism and pro-inflammatory activity. However, the mechanism of adiponectin performance within arthritic inflammation remains unclear. In this study, we observed the effect of adiponectin on the expression of oncostatin M (OSM), a pro-inflammatory cytokine, in human osteoblastic cells. Pretreatment of cells with inhibitors of phosphatidylinositol 3-kinase (PI3K), Akt, and nuclear factor (NF)-κB reduced the adiponectin-induced OSM expression in osteoblasts. Stimulation of the cells with adiponectin increased phosphorylation of PI3K, Akt, and p65. Adiponectin treatment of osteoblasts increased OSM-luciferase activity and p65 binding to NF-κB on the OSM promoter. Our results indicate that adiponectin increased OSM expression via the PI3K, Akt, and NF-κB signaling pathways in osteoblastic cells, suggesting that adiponectin is a novel target for arthritis treatment. PMID:26712749

  16. Maternal Overweight Programs Insulin and Adiponectin Signaling in the Offspring

    PubMed Central

    Shankar, Kartik; Kang, Ping; Harrell, Amanda; Zhong, Ying; Marecki, John C.; Ronis, Martin J. J.; Badger, Thomas M.

    2010-01-01

    Gestational exposure to maternal overweight (OW) influences the risk of obesity in adult life. Male offspring from OW dams gain greater body weight and fat mass and develop insulin resistance when fed high-fat diets (45% fat). In this report, we identify molecular targets of maternal OW-induced programming at postnatal d 21 before challenge with the high-fat diet. We conducted global transcriptome profiling, gene/protein expression analyses, and characterization of downstream signaling of insulin and adiponectin pathways in conjunction with endocrine and biochemical characterization. Offspring born to OW dams displayed increased serum insulin, leptin, and resistin levels (P < 0.05) at postnatal d 21 preceding changes in body composition. A lipogenic transcriptome signature in the liver, before development of obesity, was evident in OW-dam offspring. A coordinated locus of 20 sterol regulatory element-binding protein-1-regulated target genes was induced by maternal OW. Increased nuclear levels of sterol regulatory element-binding protein-1 and recruitment to the fatty acid synthase promoter were confirmed via ELISA and chromatin immunoprecipitation analyses, respectively. Higher fatty acid synthase and acetyl coenzyme A carboxylase protein and pAKT (Thr308) and phospho-insulin receptor-β were confirmed via immunoblotting. Maternal OW also attenuated AMP kinase/peroxisome proliferator-activated receptor-α signaling in the offspring liver, including transcriptional down-regulation of several peroxisome proliferator-activated receptor-α-regulated genes. Hepatic mRNA and circulating fibroblast growth factor-21 levels were significantly lower in OW-dam offspring. Furthermore, serum levels of high-molecular-weight adiponectin (P < 0.05) were decreased in OW-dam offspring. Phosphorylation of hepatic AMP-kinase (Thr172) was significantly decreased in OW-dam offspring, along with lower AdipoR1 mRNA. Our results strongly suggest that gestational exposure to maternal

  17. Adiponectin treatment attenuates inflammatory response during early sepsis in obese mice

    PubMed Central

    Wang, XianFeng; Buechler, Nancy L; Yoza, Barbara K; McCall, Charles E; Vachharajani, Vidula

    2016-01-01

    Background Morbid obesity increases the cost of care in critically ill patients. Sepsis is the leading cause of death in noncoronary intensive care units. Circulating cell–endothelial cell interactions in microcirculation are the rate-determining factors in any inflammation; obesity increases these interactions further. Adiponectin deficiency is implicated in increased cardiovascular risk in obese patients. We have shown that adiponectin deficiency increases microvascular dysfunction in early sepsis. In the present study, we investigated the effect of adiponectin replacement on nutritionally obese mice with early sepsis. Methods We used cecal ligation and puncture model of sepsis in mice with diet-induced obesity (DIO) vs control diet (CTRL), with or without adiponectin treatment. We studied leukocyte/platelet adhesion in the cerebral microcirculation in early sepsis. We also studied the effect of adiponectin on free fatty acid (FFA)-fed and lipopolysaccharide-stimulated bone marrow-derived macrophages (BMDM) for mechanistic studies. Results Leukocyte and platelet adhesion increased in the cerebral microcirculation of DIO and CTRL mice with early sepsis vs. sham; moreover cell adhesion in DIO-sepsis group was significantly higher than in the CTRL-sepsis group. Adiponectin replacement decreased leukocyte/platelet adhesion in CTRL and DIO mice. In FFA-fed BMDM, adiponectin treatment decreased tumor necrosis factor-alpha mRNA expression and increased sirtuin-1 (SIRT1) mRNA expression. Furthermore, using BMDM from SIRT1 knockout mice, we showed that the adiponectin treatment decreased inflammatory response in FFA-fed BMDM via SIRT1-dependent and -independent pathways. Conclusion Adiponectin replacement attenuates microvascular inflammation in DIO-sepsis mice. Mechanistically, adiponectin treatment in FFA-fed mouse macrophages attenuates inflammatory response via SIRT1-dependent and -independent pathways. PMID:27785087

  18. Supplementation with conjugated linoleic acids extends the adiponectin deficit during early lactation in dairy cows.

    PubMed

    Singh, Shiva P; Häussler, Susanne; Heinz, Johanna F L; Saremi, Behnam; Mielenz, Birgit; Rehage, Jürgen; Dänicke, Sven; Mielenz, Manfred; Sauerwein, Helga

    2014-03-01

    Decreasing insulin sensitivity (IS) in peripheral tissues allows for partitioning nutrients towards the mammary gland. In dairy cows, extensive lipid mobilization and continued insulin resistance (IR) are typical for early lactation. Adiponectin, an adipokine, promotes IS. Supplementation with conjugated linoleic acids (CLA) in rodents and humans reduces fat mass whereby IR and hyperinsulinemia may occur. In dairy cows, CLA reduce milk fat, whereas body fat, serum free fatty acids and leptin are not affected. We aimed to investigate the effects of CLA supplementation on serum and adipose tissue (AT) adiponectin concentrations in dairy cows during the lactation driven and parity modulated changes of metabolism. High yielding cows (n=33) were allocated on day 1 post partum to either 100 g/day of a CLA mixture or a control fat supplement (CON) until day 182 post partum. Blood and subcutaneous (sc) AT (AT) biopsy samples were collected until day 252 post partum to measure adiponectin. Serum adiponectin decreased from day 21 pre partum reaching a nadir at calving and thereafter increased gradually. The distribution of adiponectin molecular weight forms was neither affected by time, parity nor treatment. Cows receiving CLA had decreased serum adiponectin concentrations whereby primiparous cows responded about 4 weeks earlier than multiparous cows. The time course of adiponectin concentrations in sc AT (corrected for residual blood) was similar to serum concentrations, without differences between CLA and CON. CLA supplementation attenuated the post partum increase of circulating adiponectin thus acting towards prolongation of peripartal IR and drain of nutrients towards the mammary gland.

  19. Associations of Adiponectin and Leptin with Incident Coronary Heart Disease and Ischemic Stroke in African Americans: The Jackson Heart Study

    PubMed Central

    Bidulescu, Aurelian; Liu, Jiankang; Chen, Zhimin; Hickson, DeMarc A.; Musani, Solomon K.; Samdarshi, Tandaw E.; Fox, Ervin R.; Taylor, Herman A.; Gibbons, Gary H.

    2013-01-01

    Background: Because the predictive significance of previously reported racial differences in leptin and adiponectin levels remains unclear, we assessed the prospective association of these adipokines with the risk of cardiovascular disease (CVD) events in African Americans, a population with a high prevalence of cardiometabolic risk factors. Methods: Serum specimens from 4,571 Jackson Heart Study participants without prevalent CVD at baseline examination (2000–2004) were analyzed for adiponectin and leptin levels. Cox proportional hazard regression models were used to estimate the associations of the two adipokines with incident coronary heart disease (CHD) and incident ischemic stroke. Results: During 6.2 years average of follow-up, 98 incident CHD and 87 incident ischemic stroke events were documented. Among study participants (64% women; mean age 54 ± 13 years), the mean (standard deviation, SD) was 6.04 (4.32) μg/mL in women and 4.03 (3.14) μg/mL in men for adiponectin and 37.35 (23.90) ng/mL in women and 11.03 (10.05) ng/mL in men for leptin. After multivariable adjustment that included age, body mass index, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, insulin resistance by homeostasis model assessment for insulin resistance, systolic blood pressure, hypertension medication, smoking, and physical activity, adiponectin was directly associated in women with incident stroke, HR = 1.41 (1.04–1.91) per one SD increase (p = 0.03), but not in men (p = 0.42). It was not associated with incident CHD in women or men. Leptin was not associated with incident CHD or incident stroke. Conclusion: In the largest community-based African American cohort, adiponectin was associated among women with a higher risk of incident stroke. Whether adiponectin harbors harmful properties, or it is produced in response to vascular inflammation to counter the atherosclerotic process, or the putative “adiponectin resistance

  20. 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.

  1. Polymorphisms in the promoter region of the adiponectin (ADIPOQ) gene are presumably associated with transcription level and carcass traits in pigs.

    PubMed

    Cieslak, J; Flisikowska, T; Schnieke, A; Kind, A; Szydlowski, M; Switonski, M; Flisikowski, K

    2013-06-01

    The main goal of this study was to screen for polymorphisms in the porcine adiponectin (ADIPOQ) gene promoter, analyse their influence on transcription and identify any association with production traits in pigs. A 1018-bp region of the ADIPOQ gene promoter was analysed in 113 pigs, and seven novel polymorphisms found. Luciferase assays were performed in HEK293 (human embryonic kidney) cells and primary porcine adipose mesenchymal stem cells (pADMSCs) to investigate their affect on promoter activity. A 16-bp indel (c.-106_-91delGCCAGGGGTGTGAGCC) was found to influence promoter strength in vitro. In the HEK293 cell line, the Del/Del genotype showed greater luciferase activity than did the Ins/Ins genotype (P < 0.01). In pADMSCs, the insertion genotype of the ADIPOQ promoter showed greater luciferase activity than did the deletion genotype (P < 0.01). An association study performed for two novel polymorphisms, c.-67G>A and the 16-bp indel, showed significant correlation with loin measurements in Polish Landrace (P < 0.05) and synthetic line 990 (P < 0.01) pigs.

  2. Adiponectin-Mediated Analgesia and Anti-Inflammatory Effects in Rat

    PubMed Central

    Iannitti, Tommaso; Graham, Annette; Dolan, Sharron

    2015-01-01

    The adipose tissue-derived protein, adiponectin, has significant anti-inflammatory properties in a variety of disease conditions. Recent evidence that adiponectin and its receptors (AdipoR1 and AdipoR2) are expressed in central nervous system, suggests that it may also have a central modulatory role in pain and inflammation. This study set out to investigate the effects of exogenously applied recombinant adiponectin (via intrathecal and intraplantar routes; 10–5000 ng) on the development of peripheral inflammation (paw oedema) and pain hypersensitivity in the rat carrageenan model of inflammation. Expression of adiponectin, AdipoR1 and AdipoR2 mRNA and protein was characterised in dorsal spinal cord using real-time polymerase chain reaction (PCR) and Western blotting. AdipoR1 and AdipoR2 mRNA and protein were found to be constitutively expressed in dorsal spinal cord, but no change in mRNA expression levels was detected in response to carrageenan-induced inflammation. Adiponectin mRNA, but not protein, was detected in dorsal spinal cord, although levels were very low. Intrathecal administration of adiponectin, both pre- and 3 hours post-carrageenan, significantly attenuated thermal hyperalgesia and mechanical hypersensitivity. Intrathecal administration of adiponectin post-carrageenan also reduced peripheral inflammation. Intraplantar administration of adiponectin pre-carrageenan dose-dependently reduced thermal hyperalgesia but had no effect on mechanical hypersensitivity and peripheral inflammation. These results show that adiponectin functions both peripherally and centrally at the spinal cord level, likely through activation of AdipoRs to modulate pain and peripheral inflammation. These data suggest that adiponectin receptors may be a novel therapeutic target for pain modulation. PMID:26352808

  3. Adiponectin and its receptors: partners contributing to the "vicious circle" leading to the metabolic syndrome?

    PubMed

    Vasseur, Francis

    2006-06-01

    Although already described five years ago, it is only from year 2000, following intensive research in the field of genetics that the adiponectin protein was related with insulin sensitivity, type 2 diabetes and the metabolic syndrome. The story began with a paradox as this protein exclusively secreted by fat tissue was dramatically decreased in patients presenting an excess of fat mass. Later this decrease was reported with insulin resistance and metabolic syndrome associated phenotypes. The search for genetic variants in the adiponectin encoding ACDC gene and epidemio genetic investigations allowed to associate genetic variations of the gene and phenotypic traits of the metabolic syndrome. One of the major points was the correlation of the levels of circulating adiponectin with insulin sensitivity, leading to a better knowledge of the role of adiponectin. Indeed it is now clearly admitted that adiponectin is an insulin sensitizing cytokine. Recently two adiponectin receptors were described and genetic variations in their genes were associated with features of the metabolic syndrome. Interactions of adiponectin with various partners are discussed in view of a better understanding of adiponectin resistance and insulin resistance.

  4. Activation of the hexosamine signaling pathway in adipose tissue results in decreased serum adiponectin and skeletal muscle insulin resistance.

    PubMed

    Hazel, Mark; Cooksey, Robert C; Jones, Deborah; Parker, Glendon; Neidigh, John L; Witherbee, Bryan; Gulve, Eric A; McClain, Donald A

    2004-05-01

    Overexpression of the rate-limiting enzyme for hexosamine synthesis (glutamine:fructose-6-phosphate amidotransferase) in muscle and adipose tissue of transgenic mice was previously shown to result in insulin resistance and hyperleptinemia. Explanted muscle from transgenic mice was not insulin resistant in vitro, suggesting that muscle insulin resistance could be mediated by soluble factors from fat tissue. To dissect the relative contributions of muscle and fat to hexosamine-induced insulin resistance, we overexpressed glutamine:fructose-6-phosphate amidotransferase 2.5-fold, specifically in fat under control of the aP2 promoter. Fasting glucose, insulin, and triglycerides were unchanged in the transgenic mice; leptin and beta-hydroxybutyrate levels were 91% and 29% higher, respectively. Fasted transgenic mice have mild glucose intolerance and skeletal muscle insulin resistance in vivo. In fasting transgenic mice, glucose disposal rates with hyperinsulinemia were decreased 27% in females and 10% in males. Uptake of 2-deoxy-D-glucose into muscle was diminished by 45% in female and 21% in male transgenics. Serum adiponectin was also lower in the fasted transgenics, by 37% in females and 22% in males. TNF alpha and resistin mRNA levels in adipose tissue were not altered in the fasted transgenics; levels of mRNA for leptin were increased and peroxisome proliferator-activated receptor gamma decreased. To further explore the relationship between adiponectin and insulin sensitivity, we examined mice that have been refed for 6 h after a 24-h fast. Refeeding wild-type mice resulted in decreased serum adiponectin and increased leptin. In transgenic mice, however, the regulation of these hormones by refeeding was lost for adiponectin and diminished for leptin. Refed transgenic female and male mice no longer exhibited decreased serum adiponectin in the refed state, and they were no longer insulin resistant as by lower or unchanged insulin and glucose levels. We conclude that

  5. Can protein levels be economically increased?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One result from the 2010 hard red winter wheat harvest was an increase of discussions on protein values across the southern great plains. The crop garnered relatively low protein values for several reasons, many of which were directly related to the weather patterns and environmental conditions. T...

  6. Dietary regulation of adiponectin by direct and indirect lipid activators of nuclear hormone receptors.

    PubMed

    Rühl, R; Landrier, J F

    2016-01-01

    Adiponectin is an adipokine mainly secreted by adipocytes that presents antidiabetic, anti-inflammatory, and antiatherogenic functions. Therefore, modulation of adiponectin expression represents a promising target for prevention or treatment of several diseases including insulin resistance and type II diabetes. Pharmacological agents such as the nuclear hormone receptor synthetic agonists like peroxisome proliferator activated receptor γ agonists are of particular interest in therapeutic strategies due to their ability to increase the plasma adiponectin concentration. Nutritional approaches are also of particular interest, especially in primary prevention, since some active compounds of our diet (notably vitamins, carotenoids, or other essential nutrients) are direct or indirect lipid-activators of nuclear hormone receptors and are modifiers of adiponectin expression and secretion. The aim of the present review is to summarize current knowledge about the nutritional regulation of adiponectin by derivatives of active compounds naturally present in the diet acting as indirect or direct activators of nuclear hormone receptors.

  7. Adiponectin deficiency contributes to the development and progression of benign prostatic hyperplasia in obesity.

    PubMed

    Fu, Shi; Xu, Huan; Gu, Meng; Liu, Chong; Wang, Qiong; Wan, Xiang; Chen, Yanbo; Chen, Qi; Peng, Yubing; Cai, Zhikang; Zhou, Juan; Wang, Zhong

    2017-03-03

    The incidence of benign prostatic hyperplasia (BPH) is increasing among obese individuals, but few studies have fully explained the underlying mechanisms. We aimed to elucidate the relationship between obesity and BPH. Herein, we show that in prostatic epithelial and stromal cells, adiponectin exerts multifunctional effects including anti-proliferation, blocking of G1/S-phase progression and the promotion of apoptosis via inhibiting the MEK-ERK-p90RSK axis. Furthermore, we found that a high-fat diet (HFD) led to adiponectin deficiency and microscopic BPH in a mouse model of obesity. And an adiponectin supplement protected the obese mice from microscopic BPH. The present study provides evidence that adiponectin is a protective regulator in the development and progression of BPH and that adiponectin deficiency causally links BPH with obesity.

  8. Adiponectin deficiency contributes to the development and progression of benign prostatic hyperplasia in obesity

    PubMed Central

    Fu, Shi; Xu, Huan; Gu, Meng; Liu, Chong; Wang, Qiong; Wan, Xiang; Chen, Yanbo; Chen, Qi; Peng, Yubing; Cai, Zhikang; Zhou, Juan; Wang, Zhong

    2017-01-01

    The incidence of benign prostatic hyperplasia (BPH) is increasing among obese individuals, but few studies have fully explained the underlying mechanisms. We aimed to elucidate the relationship between obesity and BPH. Herein, we show that in prostatic epithelial and stromal cells, adiponectin exerts multifunctional effects including anti-proliferation, blocking of G1/S-phase progression and the promotion of apoptosis via inhibiting the MEK-ERK-p90RSK axis. Furthermore, we found that a high-fat diet (HFD) led to adiponectin deficiency and microscopic BPH in a mouse model of obesity. And an adiponectin supplement protected the obese mice from microscopic BPH. The present study provides evidence that adiponectin is a protective regulator in the development and progression of BPH and that adiponectin deficiency causally links BPH with obesity. PMID:28256562

  9. Adiponectin and adiponectin receptor system in the rat adrenal gland: ontogenetic and physiologic regulation, and its involvement in regulating adrenocortical growth and steroidogenesis.

    PubMed

    Paschke, Lukasz; Zemleduch, Tomasz; Rucinski, Marcin; Ziolkowska, Agnieszka; Szyszka, Marta; Malendowicz, Ludwik K

    2010-09-01

    Adiponectin (ADN) is a regulatory peptide secreted mostly by adipose tissue and acting via two receptors: AdipoR1 and AdipoR2. Our aim was to investigate expression of adiponectin system genes in the rat adrenal gland as well as its ontogenetic and physiological control. Furthermore, we examined the effects of acute and prolonged activation of HPA axis on ADN system in adipose tissue. By means of QPCR, ADN and AdipoR1 expression was demonstrated in rat adrenal cortex both at mRNA and protein levels, while AdipoR2 could only be detected at mRNA levels. ADN expression level was significantly upregulated in a developing and regenerating adrenal cortex. Globular domain of adiponectin at 10(-9) M stimulated corticosterone output and BrdU incorporation by cultured rat adrenocortical cells. Moreover, both acute (ACTH and ether stress) and prolonged (ACTH) adrenal stimulation resulted in lowered ADN levels, while expression of AdipoR1 and AdipoR2 was upregulated by the acute treatment. Depending on its site of origin, visceral (VAT) or subcutaneous (SAT) adipose tissue responded differently to alterations in HPA axis. VAT expression of ADN and its receptors remained almost unchanged by experimental manipulations. In SAT, on the other hand, expression of ADN and AdipoR2 was markedly increased by ACTH treatment and stress, while dexamethasone suppressed ADN and AdipoR1 mRNA levels. The results of this study provide new evidence for direct and indirect interactions between adipokines and HPA axis.

  10. Effect of peripheral kisspeptin administration on adiponectin, leptin, and resistin secretion under fed and fasting conditions in the adult male rhesus monkey (Macaca mulatta).

    PubMed

    Wahab, F; Bano, R; Jabeen, S; Irfan, S; Shahab, M

    2010-07-01

    In the last few years, kisspeptin-KISS1R signaling has appeared as a major regulator of the reproductive function in several vertebrate species. However, KISS1(encoding kisspeptin) and its putative receptor, KISS1R, are expressed in several other tissues. Adipose tissue, which secretes many peptides with diverse functions in normal physiology, expresses KISS1, which is modulated by gonadal steroids as well as by body nutritional status. Similarly, KISS1Rexpression is also found in adipose tissue, but the local role of kisspeptin in adipocyte function is currently unknown. Therefore, in the present study the effects of exogenous human kisspeptin-10 (KP10) were studied on three important adipokines, namely, adiponectin, leptin, and resistin in a set of four chair-restraint habituated intact adult male rhesus monkeys under; 1) normal fed conditions, 2) 24-h fasting conditions, and 3) 48-h fasting conditions. Plasma resistin and leptin levels decreased (p<0.01), whereas adiponectin levels increased (p<0.05) in fasted monkeys. Kisspeptin administration significantly increased (p<0.05) mean plasma adiponectin levels under fed and 24-h fasting conditions as compared to pretreatment or vehicle-treatment levels. A stimulatory effect was also observed on the 48-h fasting stimulated plasma adiponectin levels, but it lacked statistical significance. In contrast, no effect of kisspeptin was observed on mean plasma leptin and resistin levels. Thus, the present study demonstrated a stimulatory effect of peripheral kisspeptin administration on the plasma adiponectin levels under fed and 24-h fasting conditions in the adult male rhesus monkey. These findings, therefore, assign a novel role to kisspeptin, a regulator of adipocyte function in higher primate.

  11. 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.

  12. 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

  13. 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

  14. Adiponectin and visfatin concentrations in children treated with valproic acid.

    PubMed

    Rauchenzauner, Markus; Haberlandt, Edda; Scholl-Bürgi, Sabine; Ernst, Barbara; Hoppichler, Fritz; Karall, Daniela; Ebenbichler, Christoph F; Rostasy, Kevin; Luef, Gerhard

    2008-02-01

    Chronic antiepileptic therapy with valproic acid (VPA) is associated with increased body weight and insulin resistance in adults and children. Attempts to determine the underlying pathophysiologic mechanisms have failed. Adipocytokines have recently been defined as a link between glucose and fat metabolism. We herein demonstrate that VPA-associated overweight is accompanied by lower adiponectin and higher leptin concentrations in children. The absence of any relationship with visfatin concentration does not suggest a role of this novel insulin-mimetic hormone in VPA-associated metabolic alterations. Therefore, adiponectin and leptin but not visfatin may be considered as potential regulators of glucose and fat metabolism during VPA-therapy.

  15. Three-month treatment with pioglitazone reduces circulating C1q-binding adiponectin complex to total-adiponectin ratio, without changes in body mass index, in people with type 2 diabetes.

    PubMed

    Nakatsuji, Hideaki; Kishida, Ken; Kobayashi, Hironori; Funahashi, Tohru; Shimomura, Iichiro

    2013-01-01

    We measured circulating C1q-binding adiponectin (C1q-APN) levels before and after 3-month treatment with pioglitazone in people with type 2 diabetes. The results indicate 3-month treatment with pioglitazone reduces circulating levels of C1q-APN/total-adiponectin ratio without changes in body mass index.

  16. Serum Adiponectin and Cardiometabolic Risk in Patients with Acute Coronary Syndromes

    PubMed Central

    Oliveira, Gustavo Bernardes de Figueiredo; França, João Ítalo Dias; Piegas, Leopoldo Soares

    2013-01-01

    Background The adipose tissue is considered not only a storable energy source, but mainly an endocrine organ that secretes several cytokines. Adiponectin, a novel protein similar to collagen, has been found to be an adipocyte-specific cytokine and a promising cardiovascular risk marker. Objectives To evaluate the association between serum adiponectin levels and the risk for cardiovascular events in patients with acute coronary syndromes (ACS), as well as the correlations between adiponectin and metabolic, inflammatory, and myocardial biomarkers. Methods We recruited 114 patients with ACS and a mean 1.13-year follow-up to measure clinical outcomes. Clinical characteristics and biomarkers were compared according to adiponectin quartiles. Cox proportional hazard regression models with Firth's penalization were applied to assess the independent association between adiponectin and the subsequent risk for both primary (composite of cardiovascular death/non-fatal acute myocardial infarction (AMI)/non-fatal stroke) and co-primary outcomes (composite of cardiovascular death/non-fatal AMI/non-fatal stroke/ rehospitalization requiring revascularization). Results There were significant direct correlations between adiponectin and age, HDL-cholesterol, and B-type natriuretic peptide (BNP), and significant inverse correlations between adiponectin and waist circumference, body weight, body mass index, Homeostasis Model Assessment (HOMA) index, triglycerides, and insulin. Adiponectin was associated with higher risk for primary and co-primary outcomes (adjusted HR 1.08 and 1.07/increment of 1000; p = 0.01 and p = 0.02, respectively). Conclusion In ACS patients, serum adiponectin was an independent predictor of cardiovascular events. In addition to the anthropometric and metabolic correlations, there was a significant direct correlation between adiponectin and BNP. PMID:24029961

  17. Effect of orlistat on periostin, adiponectin, inflammatory markers and ultrasound grades of fatty liver in obese NAFLD patients

    PubMed Central

    Ali Khan, Rashid; Kapur, Prem; Jain, Abhinav; Farah, Farrukh; Bhandari, Uma

    2017-01-01

    Orlistat is recommended in the treatment of obesity, which is an independent risk factor for nonalcoholic fatty liver disease (NAFLD). The reported findings of orlistat in NAFLD are divisive. Recently, periostin is identified as an important regulatory molecule in the pathogenesis of obesity-induced fatty liver. Therefore, this study aimed to evaluate the potential effects of orlistat in the treatment of NAFLD. A 16-week prospective observational study was conducted, with obese NAFLD patient (n=77) receiving orlistat (120 mg capsules, three times a day) with hypocaloric diet or hypocaloric diet only. Grades of fatty liver were determined using ultrasound (US) echogenicity of liver; serum levels of periostin, adiponectin, tumor necrosis factor (TNF)-α and interleukin-6 were determined using ELISA kits at 0 and 16 weeks. Correlations of US grades of fatty liver with these biomarkers were also determined. Orlistat significantly reversed the US grades of fatty liver (P=0.016), decreased serum levels of periostin (P=0.030) and TNF-α (P=0.040), and increased serum adiponectin levels (P<0.001) when compared with hypocaloric diet only. Serum interleukin-6 levels were not found to be significantly different in both groups after the treatment. In the orlistat group, the degree of reduction in grades of fatty liver was found to be positively correlated with the changes in serum levels of periostin (rs=0.306, P=0.041) and adiponectin (rs=0.314, P=0.036), whereas the associations were insignificant with the change in serum levels of TNF-α (rs=0.053, P=0.729). Mild gastrointestinal side effects (20%) were reported in the orlistat group. In conclusion, orlistat is effective in the treatment of NAFLD patients without fibrosis. This study demonstrated a positive association between the reduction of fatty infiltration in the liver and the changes in serum levels of periostin and adiponectin in obese NAFLD patients. PMID:28260907

  18. Preliminary evidence of genetic determinants of adiponectin response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adiponectin is an adipose-secreted protein that has been linked to changes in insulin sensitivity, high-density lipoprotein cholesterol levels, and inflammatory patterns. Although fenofibrate therapy can raise adiponectin levels, treatment response is heterogeneous and heritable, suggesting a role f...

  19. Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease

    PubMed Central

    Persson, Jonas; Strawbridge, Rona J; McLeod, Olga; Gertow, Karl; Silveira, Angela; Baldassarre, Damiano; Van Zuydam, Natalie; Shah, Sonia; Fava, Cristiano; Gustafsson, Stefan; Veglia, Fabrizio; Sennblad, Bengt; Larsson, Malin; Sabater-Lleal, Maria; Leander, Karin; Gigante, Bruna; Tabak, Adam; Kivimaki, Mika; Kauhanen, Jussi; Rauramaa, Rainer; Smit, Andries J; Mannarino, Elmo; Giral, Philippe; Humphries, Steve E; Tremoli, Elena; de Faire, Ulf; Lind, Lars; Ingelsson, Erik; Hedblad, Bo; Melander, Olle; Kumari, Meena; Hingorani, Aroon; Morris, Andrew D; Palmer, Colin N A; Lundman, Pia; Öhrvik, John; Söderberg, Stefan; Hamsten, Anders

    2015-01-01

    Background Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT. Methods and Results Baseline plasma adiponectin concentration was tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n =1777; men, n =1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation IMT after adjustment for established risk factors (β =−0.018, P<0.001) in men but not in women (β =−0.006, P =0.185; P for interaction =0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (β =−0.0022, P =0.047), whereas no association was seen in women (0.0007, P =0.475; P for interaction =0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82, 95% CI 0.54 to 1.25). A gene score of adiponectin-raising alleles in 6 loci, reported recently in a large multi-ethnic meta-analysis, was inversely associated with baseline mean bifurcation IMT in men (β =−0.0008, P =0.004) but not in women (β =−0.0003, P =0.522; P for interaction =0.007). Conclusions This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted. PMID:26276317

  20. Succination of thiol groups in adipose tissue proteins in diabetes: succination inhibits polymerization and secretion of adiponectin.

    PubMed

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

    2009-09-18

    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 approximately 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.

  1. Effect of Walking Exercise on Changes in Cardiorespiratory Fitness, Metabolic Syndrome Markers, and High-molecular-weight Adiponectin in Obese Middle-aged Women.

    PubMed

    Kim, Dae-Young; Seo, Byoung-Do; Kim, Dong-Je

    2014-11-01

    [Purpose] The purpose of this study was to assess the effect of a 24-week exercise intervention on cardiorespiratory fitness, metabolic syndrome markers, and high-molecular-weight (HMW) adiponectin among obese middle-aged women. [Subjects] The subjects were 14 obese middle-aged women. [Methods] The exercise program involved walking at 50-60% of the maximum oxygen consumption, 3 times a week, for 24 weeks. Body composition analysis, blood pressure measurements, and blood analysis were performed before the exercise program and at weeks 6, 12, 18, and 24. [Results] The results showed that after 24 weeks in the exercise program, the obesity indices and metabolic risk factors, namely, weight, body fat, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, and triglycerides decreased significantly, whereas HDLC, a metabolic improvement factor, increased significantly. Additionally, VO2max increased significantly, together with the level of total and HMW adiponectins. Correlation analysis of the changes in measured variables (∆ score) during resulting from the 24-week exercise program showed that body fat had a significant negative correlation and VO2max had a significant positive correlation with HMW adiponectin. [Conclusion] Among obese middle-aged women, regular exercise increases cardiorespiratory fitness and HMW adiponectin expression and therefore can be effective in the prevention and treatment of obesity and metabolic syndrome.

  2. 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

  3. Differential Role of Leptin and Adiponectin in Cardiovascular System

    PubMed Central

    Ghantous, C. M.; Azrak, Z.; Hanache, S.; Abou-Kheir, W.; Zeidan, A.

    2015-01-01

    Leptin and adiponectin are differentially expressed adipokines in obesity and cardiovascular diseases. Leptin levels are directly associated with adipose tissue mass, while adiponectin levels are downregulated in obesity. Although significantly produced by adipocytes, leptin is also produced by vascular smooth muscle cells and cardiomyocytes. Plasma leptin concentrations are elevated in cases of cardiovascular diseases, such as hypertension, congestive heart failure, and myocardial infarction. As for the event of left ventricular hypertrophy, researchers have been stirring controversy about the role of leptin in this form of cardiac remodeling. In this review, we discuss how leptin has been shown to play an antihypertrophic role in the development of left ventricular hypertrophy through in vitro experiments, population-based cross-sectional studies, and longitudinal cohort studies. Conversely, we also examine how leptin may actually promote left ventricular hypertrophy using in vitro analysis and human-based univariate and multiple linear stepwise regression analysis. On the other hand, as opposed to leptin's generally detrimental effects on the cardiovascular system, adiponectin is a cardioprotective hormone that reduces left ventricular and vascular hypertrophy, oxidative stress, and inflammation. In this review, we also highlight adiponectin signaling and its protective actions on the cardiovascular system. PMID:26064110

  4. 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.

  5. Adiponectin concentration is associated with muscle insulin sensitivity, AMPK phosphorylation, and ceramide content in skeletal muscles of men but not women.

    PubMed

    Høeg, Louise D; Sjøberg, Kim A; Lundsgaard, Anne-Marie; Jordy, Andreas B; Hiscock, Natalie; Wojtaszewski, Jørgen F P; Richter, Erik A; Kiens, Bente

    2013-03-01

    Adiponectin is an adipokine that regulates metabolism and increases insulin sensitivity. Mechanisms behind this insulin-sensitizing effect have been investigated in rodents, but little is known in humans, especially in skeletal muscle. Women have higher serum concentrations of adiponectin than men and are generally more insulin sensitive in skeletal muscle than men. We show here that large differences exist between men and women with regard to apparent adiponectin regulation of insulin-stimulated glucose uptake in skeletal muscle. Serum adiponectin was significantly associated with leg glucose uptake in healthy, young, lean men, but the association was absent in women. In addition, serum adiponectin was significantly associated with AMP-activated protein kinase (AMPK) phosphorylation in skeletal muscles of men but not in women. Serum adiponectin was also significantly, negatively associated with skeletal muscle ceramide content in men only, and interestingly, ceramide content was negatively associated with adiponectin receptor 1 (AdipoR1) expression in skeletal muscles of men. Women had lower AdipoR1 expression in skeletal muscle and a lower percentage of glycolytic adiponectin-sensitive type 2 muscle fibers than men. These associations suggest that the insulin-sensitizing effect of adiponectin on human male skeletal muscles may be mediated via AdipoR1 to activation of AMPK, leading to lowering of ceramide content. The lower skeletal muscle AdipoR1 protein expression and lower expression of adiponectin-sensitive type 2 muscle fibers in women than in men may explain the apparent lesser sensitivity to adiponectin in women.

  6. Profile of leptin, adiponectin, and body fat in patients with hyperprolactinemia: Response to treatment with cabergoline

    PubMed Central

    Pala, Nazir Ahmad; Laway, Bashir Ahmad; Misgar, Raiz Ahmad; Shah, Zaffar Amin; Gojwari, Tariq A.; Dar, Tariq A.

    2016-01-01

    Introduction: Though hypoadiponectinemia and leptin resistance have been proposed as potential factors for weight gain in patients with hyperprolactinemia (HPL), the effects of HPL and cabergoline on these adipocyte-derived hormones are not clear. Aims of this study were (i) to assess the alterations of body fat, leptin, and adiponectin in patients with HPL (ii) effect of cabergoline treatment on these parameters. Methods: Nineteen consecutive patients with prolactinoma (median prolactin [PRL] 118.6 (interquartile range: 105.3) μg/L) and 20 controls were studied in a nonrandomized matched prospective design. The controls were age, gender, and body mass index (BMI) matched. Anthropometric data, metabolic variables, leptin, and adiponectin were studied at baseline and 3 and 6 months after cabergoline treatment. Results: Patients with prolactinoma had increased level of fasting plasma glucose (P < 0.001) as compared to age-, gender-, and BMI-matched healthy controls. Estradiol concentration of controls was higher than that of patients (P = 0.018). Patients with prolactinoma had higher levels of leptin (P = 0.027) as compared to healthy controls without a significant difference in adiponectin levels. There was a significant decrease of body weight at 3 months (P = 0.029), with a further decline at 6 months (P < 0.001) of cabergoline therapy. Furthermore, there was a significant decrement of BMI (P < 0.001), waist circumference (P = 0.003), waist-hip ratio (P = 0.03), total body fat (P = 0.003), plasma glucose (P < 0.001), leptin levels (P = 0.013), and an increase in estradiol concentration (P = 0.03) at 6 months of cabergoline treatment. Conclusion: Patients with prolactinoma have adverse metabolic profile compared to matched controls. Normalization of PRL with cabergoline corrects all the metabolic abnormalities. PMID:27042412

  7. Adipokine regulation of colon cancer: adiponectin attenuates interleukin-6-induced colon carcinoma cell proliferation via STAT-3.

    PubMed

    Fenton, Jenifer I; Birmingham, Janette M

    2010-07-01

    Obesity results in increased circulating levels of specific adipokines, which are associated with colon cancer risk. The disease state is associated with increased leptin, insulin, IGF-1, and IL-6. Conversely, adiponectin levels are decreased in obese individuals. Previously, we demonstrated adipokine-enhanced cell proliferation in preneoplastic, but not normal, colon epithelial cells, demonstrating a differential effect of adipokines on colon cancer progression in vitro. Using a model of late stage carcinoma cancer cell, namely murine MC-38 colon carcinoma cells, we compared the effect of obesity-associated adipokines (leptin, insulin, IGF-1, and IL-6) on MC-38 cell proliferation and determined whether adiponectin (full length or globular) could modulate adipokine-induced cell proliferation. We show that insulin and IL-6, but not leptin and IGF-1, induce proliferation in MC-38 cells. Adiponectin treatment of MC-38 cells did not inhibit insulin-induced cell proliferation but did inhibit IL-6-induced cell proliferation by decreasing STAT-3 phosphorylation and activation. Nitric oxide (NO) production was increased in MC-38 cells treated with IL-6; co-treatment with adiponectin blocked IL-6-induced iNOS and subsequent NO production. These data are compared to previously reported findings from our laboratory using the YAMC (model normal colon epithelial cells) and IMCE (model preneoplastic) cells. The cell lines are utilized to construct a model summarizing the hormonal consequences of obesity and the impact on the differential regulation of colon epithelial cells along the continuum to carcinoma. These data, taken together, highlight mechanisms involved in obesity-associated cancers and may lead to potential-targeted therapies.

  8. Clinical insights from adiponectin analysis in breast cancer patients reveal its anti-inflammatory properties in non-obese women.

    PubMed

    Panis, C; Herrera, A C S A; Aranome, A M F; Victorino, V J; Michelleti, P L; Morimoto, H K; Cecchini, A L; Simão, A N C; Cecchini, R

    2014-01-25

    Adiponectin is a cytokine reported as a determinant of poor prognosis in women with breast cancer. However, because data regarding its role in breast cancer have been obtained primarily from studies employing overweight or obese women, the adiponectin profile in non-obese women is poorly understood. In this study, we determined adiponectin levels in plasma from non-obese women with breast cancer and investigated a possible correlation with systemic inflammatory status. We determined the plasma adiponectin levels as well as biochemical and oxidative stress parameters in 80 women. Our results revealed that plasma adiponectin levels were affected by chemotherapy, estrogen receptor status, and disease progression. Adiponectin was positively correlated with antioxidant levels, without affecting either the metastatic behavior of disease or patient outcome. These findings highlight adiponectin as a novel player in the endocrine signaling that modulates the oxidative inflammatory response in human breast cancer, and contribute to the understanding of the role of adiponectin in pathological conditions in non-obese women.

  9. Promotion of adiponectin multimerization by emodin: a novel AMPK activator with PPARγ-agonist activity.

    PubMed

    Chen, Zhifen; Zhang, Lu; Yi, Junyang; Yang, Zhuanbo; Zhang, Zhijie; Li, Zhen

    2012-11-01

    Adiponectin is an important insulin-sensitizing adipokine with multiple beneficial effects on obesity-associated medical complications. It is secreted from adipocytes into circulation as high, medium, and low molecular weight forms (HMW, MMW, and LMW). Each oligomeric form of adiponectin exerts non-overlapping biological functions, with the HMW oligomer possessing the most potent insulin-sensitizing activity. In this study, we reported that emodin, a natural product and active ingredient of various Chinese herbs, activates AMPK in both 3T3-L1 adipocytes and 293T cells. Activation of AMPK by emodin promotes the assembly of HMW adiponectin and increases the ratio of HMW adiponectin to total adiponectin in 3T1-L1 adipocytes. Emodin might activate AMPK by an indirect mechanism similar to berberine. We also found that emodin activates PPARγ and promotes differentiation and adiponectin expression during differentiation of 3T3-L1 preadipocytes. Therefore, emodin is a novel AMPK activator with PPARγ-agonist activity. Our results demonstrate that the effects of emodin on adiponectin expression and multimerization are the ultimate effects resulting from both AMPK activation and PPARγ activation. The dual-activity makes emodin or the derivatives potential drug candidates for the treatment of type 2 diabetes and other obesity-related metabolic diseases.

  10. The effect of low calorie diet on adiponectin concentration: a systematic review and meta-analysis.

    PubMed

    Salehi-Abargouei, A; Izadi, V; Azadbakht, L

    2015-07-01

    Adiponectin secreted from adipose tissue is proposed to be inversely related to the body fat mass. However, the magnitude of the effect of low calorie diet on adiponectin concentrations remains unknown. The present study was aimed to conduct a systematic review and meta-analysis on clinical trials that access the effect of low calorie diet on adiponectin concentration. We searched PubMed, SCOPUS, ISI web of science, and Google scholar for RCTs until January 2015. Totally, 13 trials were found, which examined the effect of low calorie diet on adiponectin concentration compared control group without low calorie diet.Our meta-analysis showed that weight loss diet can substantially increase the adiponectin concentration in overall (Hedges' g=0.34, 95% CI:0.17-0.50, p<0.001). Subgroup analysis also revealed that the low calorie diet can substantially enhance adiponectin concentrations when prescribed for ≤16 weeks (Hedges' g=0.48, 95% CI: 0.12-0.83, p=0.01) compared to >16 weeks (Hedges' g=0.30, 95% CI: 0.11-0.48, p=0.002). Weight loss diet beneficially affects blood adiponectin concentrations. More clinical trials are recommended to clear this effect among different genders and nationalities, and assess the magnitude of the effect based on changes in fat mass.

  11. Relationship of serum adiponectin and resistin to glucose intolerance and fat topography in south-Asians

    PubMed Central

    Wasim, Hanif; Al-Daghri, Nasser M; Chetty, Raja; McTernan, Phillip G; Barnett, A H; Kumar, Sudhesh

    2006-01-01

    Objectives South-Asians have lower adiponectin levels compared to Caucasians. It was not clear however, if this intrinsic feature is related to aspects of glucose metabolism. This study aims to determine the relationship between body fat distribution and adipocytokine in South-Asian subjects by measuring serum adipocytokines, adiposity, insulinemia, and glucose tolerance levels. Methods In this cross-sectional study, 150 South-Asians (80 males, 70 females) were included, 60 had NGT (Control group, Age 51.33 ± 11.5, BMI 27 ± 2.3), 60 had IGT (Age 57.7 ± 12.5, BMI 27.2 ± 2.7), 30 had type 2 DM (Age 49.5 ± 10.9, BMI 28 ± 1.7). Measures of adiposity, adipocytokines and other metabolic parameters were determined. Parameters were measured using the following: a) Plasma glucose by glucose oxidase method b) CRP by immunoturbidimetric method (Roche/Hitachi analyser) c) insulin by Medgenix INS-ELISA immunoenzymetric assay by Biosource (Belgium) d) Leptin, Adiponectin by radioimmunoassay kits by Linco Research (St. Charles MO) e) Resistin by immunoassay kits by Phoenix Pharmaceuticals INC (530 Harbor Boulevard, Belmont CA 94002, USA). Results Adiponectin concentrations were highest in NGT, decreased in IGT and lowest in DMT2, (both p < 0.01). Leptin was significantly higher in DMT2 than IGT and NGT p = 0.02 and 0.04 respectively. There was a significant positive relationships between log adiponectin and 2-hr insulin values, p = 0.028 and history of hypertensions and a ischemic heart disease p = 0.008 with R = 0.65. There was a significant inverse correlation between log adiponectin and resistin, p < 0.01. Conclusion Resistin levels had an inverse correlation with adiponectin levels, indicating an inverse relationship between pro-inflammatory cytokines and adiponectin. Adiponectin levels were related to glucose tolerance. PMID:16669997

  12. Dermal Lipogenesis Inhibits Adiponectin Production in Human Dermal Fibroblasts while Exogenous Adiponectin Administration Prevents against UVA-Induced Dermal Matrix Degradation in Human Skin

    PubMed Central

    Fang, Chien-Liang; Huang, Ling-Hung; Tsai, Hung-Yueh; Chang, Hsin-I

    2016-01-01

    Adiponectin is one of the most abundant adipokines from the subcutaneous fat, and regulates multiple activities through endocrine, paracrine, or autocrine mechanisms. However, its expression in adipogenic induced fibroblasts, and the potential role in photoaging has not been determined. Here, human dermal fibroblasts, Hs68, were presented as a cell model of dermal lipogenesis through stimulation of adipogenic differentiation medium (ADM). Similar to other studies in murine pre-adipocyte models (i.e., 3T3-L1), Hs68 fibroblasts showed a tendency to lipogenesis based on lipid accumulation, triglyceride formation, and the expressions of PPAR-γ, lipoprotein lipase (LPL), and FABP4 mRNA. As expected, ADM-treated fibroblasts displayed a reduction on adiponectin expression. Next, we emphasized the photoprotective effects of adiponectin against UVA-induced damage in Hs68 fibroblasts. UVA radiation can downregulate cell adhesion strength and elastic modulus of Hs68 fibroblasts. Moreover, UVA radiation could induce the mRNA expressions of epidermal growth factor receptor (EGFR), adiponectin receptor 1 (AdipoR1), matrix metalloproteinase-1 (MMP-1), MMP-3, and cyclooxygenase-2 (COX-2), but downregulate the mRNA expressions of type I and type III collagen. On the other hand, post-treatment of adiponectin can partially overcome UVA-induced reduction in the cell adhesion strength of Hs68 fibroblasts through the activation of AdipoR1 and the suppression of EGF-R. In addition, post-treatment of adiponectin indicated the increase of type III collagen and elastin mRNA expression and the decrease of MMP-1 and MMP-3 mRNA expression, but a limited degree of recovery of elastic modulus on UVA-irradiated Hs68 fibroblasts. Overall, these results suggest that dermal lipogenesis may inhibit the expression of adiponectin while exogenous adiponectin administration prevents against UVA-induced dermal matrix degradation in Hs68 fibroblasts. PMID:27428951

  13. Dermal Lipogenesis Inhibits Adiponectin Production in Human Dermal Fibroblasts while Exogenous Adiponectin Administration Prevents against UVA-Induced Dermal Matrix Degradation in Human Skin.

    PubMed

    Fang, Chien-Liang; Huang, Ling-Hung; Tsai, Hung-Yueh; Chang, Hsin-I

    2016-07-14

    Adiponectin is one of the most abundant adipokines from the subcutaneous fat, and regulates multiple activities through endocrine, paracrine, or autocrine mechanisms. However, its expression in adipogenic induced fibroblasts, and the potential role in photoaging has not been determined. Here, human dermal fibroblasts, Hs68, were presented as a cell model of dermal lipogenesis through stimulation of adipogenic differentiation medium (ADM). Similar to other studies in murine pre-adipocyte models (i.e., 3T3-L1), Hs68 fibroblasts showed a tendency to lipogenesis based on lipid accumulation, triglyceride formation, and the expressions of PPAR-γ, lipoprotein lipase (LPL), and FABP4 mRNA. As expected, ADM-treated fibroblasts displayed a reduction on adiponectin expression. Next, we emphasized the photoprotective effects of adiponectin against UVA-induced damage in Hs68 fibroblasts. UVA radiation can downregulate cell adhesion strength and elastic modulus of Hs68 fibroblasts. Moreover, UVA radiation could induce the mRNA expressions of epidermal growth factor receptor (EGFR), adiponectin receptor 1 (AdipoR1), matrix metalloproteinase-1 (MMP-1), MMP-3, and cyclooxygenase-2 (COX-2), but downregulate the mRNA expressions of type I and type III collagen. On the other hand, post-treatment of adiponectin can partially overcome UVA-induced reduction in the cell adhesion strength of Hs68 fibroblasts through the activation of AdipoR1 and the suppression of EGF-R. In addition, post-treatment of adiponectin indicated the increase of type III collagen and elastin mRNA expression and the decrease of MMP-1 and MMP-3 mRNA expression, but a limited degree of recovery of elastic modulus on UVA-irradiated Hs68 fibroblasts. Overall, these results suggest that dermal lipogenesis may inhibit the expression of adiponectin while exogenous adiponectin administration prevents against UVA-induced dermal matrix degradation in Hs68 fibroblasts.

  14. Effects of rosglitazone on plasma adiponectin, insulin sensitivity, and insulin secretion in high-risk African Americans with impaired glucose tolerance test and type 2 diabetes.

    PubMed

    Osei, Kwame; Gaillard, Trudy; Kaplow, June; Bullock, Matthew; Schuster, Dara

    2004-12-01

    We examined the metabolic effects of rosiglitazone therapy on glucose control, insulin sensitivity, insulin secretion, and adiponectin in first-degree relatives of African Americans with type 2 diabetes (DM) with impaired glucose tolerance (IGT) and DM for 3 months. The study was comprised of 12 first-degree relatives with IGT, 17 newly diagnosed DM, and 19 healthy relatives with normal glucose tolerance (NGT). Oral glucose tolerance test (OGTT) was performed before and after 3 months of rosiglitazone therapy (4 to 8 mg/d) in patients with IGT and DM. Serum glucose, insulin, C-peptide, and adiponectin levels were measured before and 2 hours during OGTT in the NGT and patients with IGT and DM. Insulin resistance index (HOMA-IR) and beta-cell function (HOMA-%B) were calculated in each subject using homeostasis model assessment (HOMA). Rosglitazone improved the overall glycemic control in the IGT and DM groups. Following rosiglitazone, the beta-cell secretion remained unchanged, while HOMR-IR was reduced in DM by 30% (4.12 +/- 1.95 v 6.33 +/- 3.54, P < .05) and the IGT group (3.78 +/- 2.45 v 4.81 +/- 3.49, P = not significant [NS]). Mean plasma adiponectin levels were significantly (P < .05) lower in the DM (6.74 +/- 1.95 microg/mL) when compared with the NGT group(9.61 +/- 5.09). Rosiglitazone significantly (P < .001) increased adiponectin levels by 2-fold in patients with IGT (22.2 +/- 10.97 microg/mL) and 2.5-fold greater in DM (15.68 +/- 8.23 microg/mL) at 3 months when compared with the 0 month. We conclude that adiponectin could play a significant role (1) in the pathogenesis of IGT and DM and (2) the beneficial metabolic effects of thiazolidinediones (TZDs) in high-risk African American patients.

  15. Reduced-energy diet improves survival of obese KKAy mice with viral myocarditis: induction of cardiac adiponectin expression.

    PubMed

    Kanda, Tsugiyasu; Saegusa, Seiichiro; Takahashi, Takashi; Sumino, Hiroyuki; Morimoto, Shigeto; Nakahashi, Takeshi; Iwai, Kunimitsu; Matsumoto, Masayuki

    2007-07-31

    Obesity is an important risk factor for heart disease. Whether weight loss affects the severity of heart failure induced by viral myocarditis is a matter of debate. We hypothesized that weight loss could improve cardiac dysfunction by inducing cardiac expression of a cardioprotective cytokine, adiponectin. We examined the relationship between weight loss by food restriction and heart failure due to viral myocarditis in obese KKAy mice. We intraperitoneally injected encephalomyocarditis virus (500 plaque-forming units/mouse) into KKAy mice fed ad libitum as a control (CF) or 60% restriction of that eaten by ad libitum (RF). The 14-day survival rate was 0% in FF, whereas it was 23% in RF (P<0.01). Heart weight/body weight ratio in RF was lower than that in FF on day 5 after viral inoculation (P<0.05). Histological scores for myocardial necrosis and inflammation on day 5 were significantly lower in RF than in FF (P<0.05). Circulating adiponectin level on day 0 was significantly elevated in RF compared with that in FF (32+9 vs. 22+2 microg/mL, P<0.05). Comparative expression of cardiac adiponectin mRNA in RF was significantly higher than that in FF (5.1+0.3 vs. 1+0.2, P<0.05). Cardiac tumor necrosis factor-alpha (TNF-alpha) mRNA in RF was significantly decreased compared with that in FF on day 5 (P<0.05). Cardiac expression of nuclear factor kappa B was reduced and that of peroxisome proliferator-activated receptor gamma mRNA was increased in RF in comparison with FF on day 0. Cardiac adiponectin mRNA was negatively correlated with cardiac TNF-alpha mRNA (r=-0.555; P=0.0097). Weight loss improved the survival and myocardial damage in obese mice with viral myocarditis, with cardiac induction of adiponectin. The induction of adiponectin might provide benefit through a cardioprotective effect against acute heart failure due to viral myocarditis in obese subjects.

  16. Attenuated improvements in adiponectin and fat loss characterize type 2 diabetes non-remission status following bariatric surgery

    PubMed Central

    Malin, Steven K.; Bena, James; Abood, Beth; Pothier, Claire E.; Bhatt, Deepak L; Nissen, Steven; Brethauer, Stacy A.; Schauer, Philip R.; Kirwan, John P.; Kashyap, Sangeeta R.

    2014-01-01

    Aim Bariatric surgery improves glycemic control, but not all patients achieve type 2 diabetes (T2D) remission. Thus, we aimed to identify metabolic determinants of T2D non-remission status following bariatric surgery at 12 and 24 months (m). Methods Forty adults (BMI: 36±3kg/m2, Age: 48±9y, HbA1c: 9.7±2%) undergoing bariatric surgery (i.e. RYGB or SG) were enrolled in STAMPEDE. T2D remission was defined as HbA1c <6.5% and fasting glucose <126 mg/dl without anti-diabetic medication. Indices of insulin secretion and sensitivity were calculated from plasma glucose, insulin and C-peptide during a 120 min MMTT. Body fat (DXA), incretins (GLP-1, GIP, ghrelin), and adipokines (adiponectin, leptin, TNF-α, hs-CRP) were also assessed. Results At 24m, 37 subjects had follow-up data (n = 18 RYGB and n = 19 SG). Bariatric surgery-induced 40% and 27% T2D remission rates at 12 and 24m, respectively. Total fat/abdominal fat loss, insulin secretion, insulin sensitivity, and β-cell function (C-peptide0–120/Glucose0–120 × Matsuda index) improved more in remitters at 12 and 24m than non-remitters. Incretin levels were unrelated to T2D remission, but, compared to non-remitters, hs-CRP decreased and adiponectin increased more in remitters. Only baseline adiponectin predicted lower HbA1c at 12 and 24m, and elevated adiponectin correlated with enhanced β-cell function, lower triglycerides and fat loss. Conclusions Smaller rises in adiponectin, a mediator of insulin action and adipose mass, depict T2D non-remission up to 2 years after bariatric surgery. Adjunctive strategies promoting greater fat loss and/or raising adiponectin may be key for higher T2D remission rates after bariatric surgery. PMID:25132119

  17. Ratiometric Measurements of Adiponectin by Mass Spectrometry in Bottlenose Dolphins (Tursiops truncatus) with Iron Overload Reveal an Association with Insulin Resistance and Glucagon

    PubMed Central

    Neely, Benjamin A.; Carlin, Kevin P.; Arthur, John M.; McFee, Wayne E.; Janech, Michael G.

    2013-01-01

    High molecular weight (HMW) adiponectin levels are reduced in humans with type 2 diabetes and insulin resistance. Similar to humans with insulin resistance, managed bottlenose dolphins (Tursiops truncatus) diagnosed with hemochromatosis (iron overload) have higher levels of 2 h post-prandial plasma insulin than healthy controls. A parallel reaction monitoring assay for dolphin serum adiponectin was developed based on tryptic peptides identified by mass spectrometry. Using identified post-translational modifications, a differential measurement was constructed. Total and unmodified adiponectin levels were measured in sera from dolphins with (n = 4) and without (n = 5) iron overload. This measurement yielded total adiponectin levels as well as site specific percent unmodified adiponectin that may inversely correlate with HMW adiponectin. Differences in insulin levels between iron overload cases and controls were observed 2 h post-prandial, but not during the fasting state. Thus, post-prandial as well as fasting serum adiponectin levels were measured to determine whether adiponectin and insulin would follow similar patterns. There was no difference in total adiponectin or percent unmodified adiponectin from case or control fasting animals. There was no difference in post-prandial total adiponectin levels between case and control dolphins (mean ± SD) at 763 ± 298 and 727 ± 291 pmol/ml, respectively (p = 0.91); however, percent unmodified adiponectin was significantly higher in post-prandial cases compared to controls (30.0 ± 6.3 versus 17.0 ± 6.6%, respectively; p = 0.016). Interestingly, both total and percent unmodified adiponectin were correlated with glucagon levels in controls (r = 0.999, p  < 0.001), but not in cases, which is possibly a reflection of insulin resistance. Although total adiponectin levels were not significantly different, the elevated percent unmodified adiponectin follows a trend similar to

  18. 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.

  19. CTX Correlation to Disease Duration and Adiponectin in Egyptian Children with T1DM

    PubMed Central

    Hashim, Amel A.; Emara, Ibrahim A.; El-Hefnawy, Mohamed H.

    2016-01-01

    Summary Background In this study, we investigated the relationship of adiponectin with bone marker changes in Egyptian children and adolescents with T1DM and the effect of disease duration on these markers, as well as the possible correlations between adiponectin and bone markers in these patients. Methods Sixty Egyptian children and adolescent patients with T1DM were studied. Serum adiponectin and collagen breakdown products (cross-linked C-terminal telopeptide of collagen type l »CTX«) were measured and compared to the results of 20 age-matched healthy controls. Results After adjustment for age, BMI, Tanner stage and gender; (total) adiponectin was significantly higher in all T1DM patients. Serum level of CTX and 25(OH)D showed a marked decrease in diabetics with disease duration > 5 years. Serum level of (total) calcium and inorganic phosphorus (Pi) did not show significant difference from control. CTX was inversely correlated to FBG and T1DM duration. Pi was inversely, while 25(OH)D was directly correlated to FBG. Total calcium showed an inverse correlation with HbA1c. FBG, TC, TAG, LDL-C were independent predictors of CTX in T1DM. Conclusions Adiponectin showed no correlation with either CTX or bone homeostatic indices. FBG, TC, TAG, LDL-C were independent predictors of CTX in T1DM. We recommend further investigation of adiponectin isoforms in a population-based study, to establish a good age- and sex-related reference.

  20. Relationship of Plasma Adiponectin and Waist-hip Ratio with Coronary Artery Disease

    PubMed Central

    Rashiti, Premtim; Elezi, Shpend; Behluli, Ibrahim; Mucaj, Sefedin

    2016-01-01

    Background: This study aimed to investigate correlation between adiponectin and waist-hip-ratio with severity of coronary artery disease (CAD). There is uncertainty about the association between circulating concentrations of adiponectin and CAD. Methods: We enrolled eighty-two consecutive patients undergoing non-urgent coronary angiography for CAD survey. According to the angiography results, the patients were divided into two groups in 1:1 ratio patients admitted with a diagnosis of CAD and non-CAD. We conducted hospital based research, involving study group with documented angiographically CAD, and control group without evidence of CAD. Angiograms were also quantified for the extent and severity of CAD by the Gensini scoring system. We measured baseline adiponectin levels in stored serum samples of all patients, anthropometric and biochemical risk factors were assessed in both groups. Results: The presence of CAD was associated with current smoking, male gender, waist–hip ratio (WHR) and left ventricular ejection fraction (LVEF). Baseline adiponectin concentrations correlated significantly in terms of the lipid parameters, positively with HDL cholesterol concentrations (r=0.327, P=0.028, P<0.05) and serum triglyceride concentrations were correlated negatively (r=-0.513, P<0.001). No significant difference between median adiponectin levels at baseline was observed between cases and controls. Conclusion: There is a significant positive correlation between waist–hip ratio and presence and severity of coronary artery disease. In conclusion, there is a significant positive correlation between adiponectin and Gensini score among Kosovar patients. PMID:28210011

  1. Adiponectin and resistin: a role in the hypothalamo-pituitary gonadal axis ?

    PubMed

    Rak, Agnieszka; Mellouk, Namya; Froment, Pascal; Dupont, Joëlle

    2017-03-22

    Adipokines, including adiponectin and resistin, are cytokines produced mainly by adipose tissue. They play a significant role in the metabolic functions that regulate insulin sensitivity and inflammation. Alteration of adiponectin and resistin plasma levels, or their expression in metabolic and gonadal tissue, are observed in some metabolic pathologies, such as obesity. Several studies have shown that these two hormones and the receptors for adiponectin, AdipoR1 and AdipoR2, are present in various reproductive tissues in both sexes of different species. Thus, these adipokines could be metabolic signals that partially explain infertility related to obesity, such as polycystic ovary syndrome (PCOS). Species and gender differences in plasma levels, tissue or cell distribution and hormonal regulation have been reported for resistin and adiponectin. Furthermore, until now, it has been unclear whether adiponectin and resistin act directly or indirectly on the hypothalamo-pituitary-gonadal axis. The objective of this review was to summarize the latest findings and particularly the species and gender differences known to date of adiponectin and resistin on female and male reproduction, based on the hypothalamo-pituitary-gonadal axis.

  2. A Comparison of the Effects of Aerobic and Intense Exercise on the Type 2 Diabetes Mellitus Risk Marker Adipokines, Adiponectin and Retinol Binding Protein-4

    PubMed Central

    Phillips, Amy; Cobbold, Christian

    2014-01-01

    With a more sedentary population comes growing rates of obesity and increased type 2 diabetes mellitus (T2DM) risk. Exercise generally induces positive changes in traditional T2DM risk markers such as lipids, glucose tolerance, and insulin sensitivity; however alterations in concentrations of many circulating cytokines and their respective receptors are also becoming apparent. These cytokines may be early-response health risk factors otherwise overlooked in traditional T2DM risk marker analysis. Plasma levels of two adipocyte-originating cytokines, adiponectin and retinol binding protein 4 (RBP-4), alter following exercise. Adiponectin has anti-inflammatory, anti-atherosclerotic, and anti-insulin resistance roles and its secretion increases with physical activity, whilst elevated RBP-4 leads to increased insulin resistance, and secretion decreases with increasing physical activity; thus these plasma adipokine levels alter favourably following exercise. Although current data are limited, they do suggest that the more intense the exercise, the greater the positive effect on plasma RBP-4 levels, whilst lower intensity aerobic exercise may positively improve adiponectin concentrations. Therefore short-duration, high intensity training may provide a time-efficient alternative to the recommended 150 min moderate aerobic exercise per week in providing positive changes in RBP-4 and other traditional T2DM risk markers and due to increased compliance give greater health benefits over the longer term. PMID:26464853

  3. 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.

  4. Cardioprotection of ischemic preconditioning in rats involves upregulating adiponectin.

    PubMed

    Wang, Hui; Wu, Wenjing; Duan, Jun; Ma, Ming; Kong, Wei; Ke, Yuannan; Li, Gang; Zheng, Jingang

    2017-02-20

    It has been reported that ischemic preconditioning (IPC) and adiponectin (APN) are cardioprotective in many cardiovascular disorders. However, whether APN mediates the effect of IPC on myocardial injury has not been elucidated. This study was conducted to investigate whether IPC affects myocardial ischemic injury by increasing APN expression. Male adult rats with cardiac knockdowns of APN and its receptors via intramyocardial small-interfering RNA injection were subjected to IPC and then myocardial infarction (MI) at 24 h post-IPC. Globular APN (gAd) was injected at 10 min before MI. APN mRNA and protein levels in myocardium as well as the plasma APN concentration were markedly high at 6 and 12 h after IPC. IPC ameliorated myocardial injury as evidenced by improved cardiac functions and a reduced infarct size. Compared with the control MI group, rats in the IPC + MI group had elevated levels of left ventricular ejection fraction and fractional shortening, and a smaller MI size (P<0.05). However, the aforementioned protective effects were ameliorated in the absence of APN and APN receptors, followed by inhibition of AMP-activated protein kinase (AMPK) phosphorylation, but reversed by gAd treatment in wild-type rats, and AMPK phosphorylation increased (P<0.05). Overall, our results suggest that the cardioprotective effects of IPC are partially due to upregulation of APN, and provide a further insight into IPC-mediated signaling effects.

  5. Effects of Adiponectin Including Reduction of Androstenedione Secretion and Ovarian Oxidative Stress Parameters In Vivo

    PubMed Central

    Comim, Fabio V.; Gutierrez, Karina; Bridi, Alessandra; Bochi, Guilherme; Chemeris, Raisa; Rigo, Melânia L.; Dau, Andressa Minussi P.; Cezar, Alfredo S.; Moresco, Rafael Noal; Gonçalves, Paulo Bayard Dias

    2016-01-01

    Adiponectin is the most abundantly produced human adipokine with anti-inflammatory, anti-oxidative, and insulin-sensitizing properties. Evidence from in vitro studies has indicated that adiponectin has a potential role in reproduction because it reduces the production of androstenedione in bovine theca cells in vitro. However, this effect on androgen production has not yet been observed in vivo. The current study evaluated the effect of adiponectin on androstenedione secretion and oxidative stress parameters in a rodent model. Seven-week-old female Balb/c mice (n = 33), previously treated with equine gonadotropin chorionic, were assigned to one of four different treatments: Group 1, control (phosphate-buffered saline); Group 2, adiponectin 0.1 μg/mL; Group 3, adiponectin 1.0 μg/mL; Group 4, adiponectin 5.0 μg/mL. After 24 h, all animals were euthanized and androstenedione levels were measured in the serum while oxidative stress markers were quantified in whole ovary tissue. Female mice treated with adiponectin exhibited a significant reduction (about 60%) in serum androstenedione levels in comparison to controls. Androstenedione levels decreased from 0.78 ± 0.4 ng/mL (mean ± SD) in controls to 0.28 ± 0.06 ng/mL after adiponectin (5 μg/mL) treatment (P = 0.01). This change in androgen secretion after 24 hours of treatment was associated with a significant reduction in the expression of CYP11A1 and STAR (but not CYP17A1). In addition, ovarian AOPP product levels, a direct product of protein oxidation, decreased significantly in adiponectin-treated mice (5 μg/mL); AOPP (mean ± SD) decreased to 4.3 ± 2.1 μmol/L in comparison with that of the controls (11.5 ± 1.7 μmol/L; P = 0.0003). Our results demonstrated for the first time that acute treatment with adiponectin reduced the levels of a direct oxidative stress marker in the ovary as well as decreased androstenedione serum levels in vivo after 24 h. PMID:27158926

  6. Globular adiponectin controls insulin-mediated vasoreactivity in muscle through AMPKα2.

    PubMed

    de Boer, Michiel P; Meijer, Rick I; Richter, Erik A; van Nieuw Amerongen, Geerten P; Sipkema, Pieter; van Poelgeest, Erik M; Aman, Jurjan; Kokhuis, Tom J A; Koolwijk, Pieter; van Hinsbergh, Victor W M; Smulders, Yvo M; Serné, Erik H; Eringa, Etto C

    2016-03-01

    Decreased tissue perfusion increases the risk of developing insulin resistance and cardiovascular disease in obesity, and decreased levels of globular adiponectin (gAdn) have been proposed to contribute to this risk. We hypothesized that gAdn controls insulin's vasoactive effects through AMP-activated protein kinase (AMPK), specifically its α2 subunit, and studied the mechanisms involved. In healthy volunteers, we found that decreased plasma gAdn levels in obese subjects associate with insulin resistance and reduced capillary perfusion during hyperinsulinemia. In cultured human microvascular endothelial cells (HMEC), gAdn increased AMPK activity. In isolated muscle resistance arteries gAdn uncovered insulin-induced vasodilation by selectively inhibiting insulin-induced activation of ERK1/2, and the AMPK inhibitor compound C as well as genetic deletion of AMPKα2 blunted insulin-induced vasodilation. In HMEC deletion of AMPKα2 abolished insulin-induced Ser(1177) phosphorylation of eNOS. In mice we confirmed that AMPKα2 deficiency decreases insulin sensitivity, and this was accompanied by decreased muscle microvascular blood volume during hyperinsulinemia in vivo. This impairment was accompanied by a decrease in arterial Ser(1177) phosphorylation of eNOS, which closely related to AMPK activity. In conclusion, globular adiponectin controls muscle perfusion during hyperinsulinemia through AMPKα2, which determines the balance between NO and ET-1 activity in muscle resistance arteries. Our findings provide a novel mechanism linking reduced gAdn-AMPK signaling to insulin resistance and impaired organ perfusion.

  7. [Adiponectin, insulin and glucose concentrations in overweight and obese subjects after a complex carbohydrates (fiber) diet].

    PubMed

    González Rodríguez, Dora Cristina; Solano R, Liseti; González Martínez, Julio César

    2009-09-01

    Adiponectin one of the cytokines secreted by the adipose tissue that regulates the energetic metabolism through glucose and insulin interactions, stimulates the oxidation of fatty acids, reduces the plasmatic triglycerides and improves glucose metabolism by increasing insulin sensibility. Serum concentrations of adiponectin, insulin and glucose were assessed in order to establish association to weight loss after a dietary regime based on consumption of complex carbohydrates (fiber) during six weeks. Overweight and obese subjects (n=56) were studied by anthropometry. Adiponectin and insulin were measured by ELISA and glucose by Colorimetry. Data was analyzed by non parametric tests to compare independent or related samples. 12 men and 44 women, aged 20 to 55 years, 17 overweight and 39 obese were assessed. Adiponectin concentration was significantly low at basal determination in all the subjects (4,47 +/- 1,64); being higher in women (4,62 +/- 1,57 vs 3,93 +/- 1,86 microU/mL in men), while glucose and insulin values were at normal range (82,46 +/-26,51 mg/dL and 14,12 +/- 10,15 microU/mL) respectively with no significant differences for sex. Overweight subjects had significantly higher adiponectin concentrations than obese participants, at all measurements. Dietary regime promoted significant increase in adiponectin concentration at second and sixth week, with a negative correlation to body mass index and gender as they lost body weight.

  8. The effects of adiponectin and leptin on human endothelial cell proliferation: a live-cell study.

    PubMed

    Alvarez, Granada; Visitación Bartolomé, M; Miana, María; Jurado-López, Raquel; Martín, Ruben; Zuluaga, Pilar; Martinez-Martinez, Ernesto; Nieto, M Luisa; Alvarez-Sala, Luis A; Millán, Jesús; Lahera, Vicente; Cachofeiro, Victoria

    2012-01-01

    The effect of adiponectin and leptin on the proliferation of the human microvascular endothelial cell line (HMEC-1) was studied in the absence or presence of fetal bovine serum (FBS). The participation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/Akt (PI-3K/Akt) pathways in this effect were evaluated. We studied the effect of both adipokines on the motility, mitosis, proliferation and cell death processes of HMEC-1 cells using live-cell imaging techniques. Adiponectin but not leptin further increased the proliferative effect induced by FBS on HMEC-1. This effect seems to be the consequence of an increase in the mitotic index in adiponectin-treated cells when compared to untreated ones. The presence of either the mitogen-activated protein kinase (MAPK) inhibitor (PD98059), or PI-3K inhibitor (LY294002), reduced the effect of adiponectin in a dose-dependent manner. Neither adipokine was able to affect HMEC-1 proliferation in FBS-free conditions. Duration of mitosis, cell motility and the cell death process were similar in all conditions. These data suggest that adiponectin and leptin exert different effects on endothelial cell function. Adiponectin was able to potentiate proliferation of HMEC-1. This effect involves the activation of both PI3-K/Akt and ERK/MAPK pathways. However, it seems to exert minimal effects on HMEC-1 function in the case of leptin.

  9. 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.

  10. Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism.

    PubMed

    Liu, Qingqing; Yuan, Bingbing; Lo, Kinyui Alice; Patterson, Heide Christine; Sun, Yutong; Lodish, Harvey F

    2012-09-04

    The effects of adiponectin on hepatic glucose and lipid metabolism at transcriptional level are largely unknown. We profiled hepatic gene expression in adiponectin knockout (KO) and wild-type (WT) mice by RNA sequencing. Compared with WT mice, adiponectin KO mice fed a chow diet exhibited decreased mRNA expression of rate-limiting enzymes in several important glucose and lipid metabolic pathways, including glycolysis, tricarboxylic acid cycle, fatty-acid activation and synthesis, triglyceride synthesis, and cholesterol synthesis. In addition, binding of the transcription factor Hnf4a to DNAs encoding several key metabolic enzymes was reduced in KO mice, suggesting that adiponectin might regulate hepatic gene expression via Hnf4a. Phenotypically, adiponectin KO mice possessed smaller epididymal fat pads and showed reduced body weight compared with WT mice. When fed a high-fat diet, adiponectin KO mice showed significantly reduced lipid accumulation in the liver. These lipogenic defects are consistent with the down-regulation of lipogenic genes in the KO mice.

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

    SciTech Connect

    Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana; Klegeris, Andis; Little, Jonathan P.

    2014-03-28

    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 observed 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.

  12. High-molecular-weight adiponectin does not predict cardiovascular events in patients with type 2 diabetes.

    PubMed

    Krzyzanowska, Katarzyna; Aso, Yoshimasa; Mittermayer, Friedrich; Inukai, Toshihiko; Brix, Johanna; Schernthaner, Guntram

    2009-04-01

    Low circulating high-molecular-weight (HMW) adiponectin might be associated with increased cardiovascular risk. This study aimed to investigate the relationship between HMW adiponectin and cardiovascular events in patients with type 2 diabetes mellitus (T2DM) with an adverse cardiovascular risk profile. The investigation took place in a specialized outpatient clinic for metabolic diseases and included 147 patients with T2DM following a cross-sectional and a prospective study protocol. Ninety patients had macrovascular disease at baseline defined as preexisting coronary artery disease, previous stroke, or peripheral artery disease. HMW adiponectin measured by enzyme-linked immunosorbent assay (Fujirebio, Tokyo, Japan) and routine clinical parameters were determined in all patients at baseline. The occurrence of new cardiovascular events (myocardial infarction, stroke, and all-cause mortality) during the follow-up period was evaluated. No significant correlations between traditional cardiovascular risk markers and HMW adiponectin could be detected. HMW adiponectin did not differ between subjects with and without macrovascular disease at baseline (3.5 [interquartile range [IQR]: 2.2-5.7] mg/L vs 4.0 [IQR: 2.5-7.1] mg/L). During a follow-up of 19.3 (IQR: 16-25) months, 61 endpoints (41 myocardial infarctions, 10 strokes, and 10 deaths) were observed. A 1-standard-deviation increment of log-transformed HMW adiponectin was not significantly associated with the occurrence of cardiovascular events (Adjusted hazard ratio [HR]: 0.95; 95% confidence interval [CI]: 0.58-1.54; P = 0.835). In conclusion, HMW adiponectin was not related to present macrovascular disease and is not associated with future cardiovascular events in high-risk patients with T2DM. It is unlikely that HMW adiponectin has significant vasoprotective effects in these patients.

  13. C-reactive protein inhibits high-molecular-weight adiponectin expression in 3T3-L1 adipocytes via PI3K/Akt pathway.

    PubMed

    Liu, Yuanxin; Liu, Cuiping; Jiang, Chao; Wang, Su; Yang, Qichao; Jiang, Dan; Yuan, Guoyue

    2016-03-25

    Adiponectin, an adipose-specific protein hormone, is secreted from white adipose tissue and involved in glucose and lipid metabolism. It is assembled into low-molecular-weight trimer (LMW), middle-molecular-weight hexameric (MMW) and high-molecular-weight (HMW), among which HMW exhibits higher activity. In this study, we proved that C-reactive protein (CRP), an inflammatory marker, inhibited adiponectin expression, especially HMW in time-and dose-dependent manners. Furthermore, CRP decreased the HMW/total adiponectin ration and reduced adiponectin assembly by increasing ERp44, and decreasing Ero1-α and DsbA-L. CRP activated pAkt, the downstream of PI3K. Inhibition of PI3K or pAkt abolished the effect of CRP. Our study suggested that CRP decreased adiponectin expression and multimerization, while CRP-induced decline in adiponectin might be mediated through the PI3K/Akt pathway.

  14. 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.

  15. 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

  16. LOW CIRCULATING MATERNAL ADIPONECTIN IN PATIENTS WITH PYELONEPHRITIS: ADIPONECTIN AT THE CROSSROADS OF PREGNANCY AND INFECTION

    PubMed Central

    Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Erez, Offer; Mittal, Pooja; Kim, Sun Kwon; Gotsch, Francesca; Lamont, Ronald; Ogge, Giovanna; Pacora, Percy; Goncalves, Luis; Kim, Chong Jai; Gomez, Ricardo; Espinoza, Jimmy; Hassan, Sonia S.; Kusanovic, Juan Pedro

    2009-01-01

    Objective An emerging theme in modern biology is that adipose tissue can respond to metabolic stress, and to inflammatory stimuli, by regulating the secretion of a complex network of soluble mediators, termed adipokines. Adiponectin, the most prevalent circulating adipokine in human, has profound insulin-sensitizing and anti-inflammatory properties. Indeed, the notion that adiponectin plays an important role in the interactions between the metabolic and the immune systems has been strongly suggested. Thus, the aim of this study was to determine if pyelonephritis during pregnancy is associated with changes in maternal serum adiponectin concentrations. Study design This cross-sectional study included women in the following groups: 1) normal pregnant women (n=200); and 2) pregnant women with pyelonephritis (n=50). Maternal plasma adiponectin concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results 1) The median maternal plasma adiponectin concentration was lower in patients with pyelonephritis than in those with a normal pregnancy (p<0.001); 2) among pregnant women with a normal weight, patients with pyelonephritis had a lower median plasma adiponectin concentration than those with a normal pregnancy (p<0.001); 3) similarly, among overweight/obese patients, those with pyelonephritis had a lower median plasma adiponectin concentration than those with a normal pregnancy (p<0.001); and 4) the presence of pyelonephritis was independently associated with maternal plasma adiponectin concentrations after adjustment for maternal age, smoking, gestational age at sampling, and pre-gestational BMI. Conclusion 1) The findings that acute pyelonephritis in pregnancy is characterized by low maternal plasma concentrations of adiponectin in both lean and overweight/obese patients are novel and concur with the anti-inflammatory properties of adiponectin; and 2) the results of this study support the notion that adiponectin may play a role in the

  17. Increased CSF levels of endorphines in chronic psychosis.

    PubMed

    Terenius, L; Wahlström, A; Lindström, L; Widerlöv, E

    1976-10-01

    The levels of two endorphines, endogenously occurring morphinomimetic peptides, were measured in serial samples of CSF from seven psychiatric patients. Four cases with chronic schizophrenia were studied before and after treatment with the antipsychotic agent clozapine (Leponex). Supernormal fraction II levels were found on at least one sampling occasion in each patient. Two patients, who responded well to clozapine treatment, showed a clear-cut drop in fraction II levels, whereas two patients showed increased levels which paralleled a deterioration of the schizophrenic symptoms. Three manic-depressive cases showed abnormally high levels of endorphine fraction I in the manic phase which declined during normal or depressed phases. Levels of fraction II varied in a less consistent manner and appeared to be at maximum during the apparently normal phases. Although preliminary, the data indicate that endorphines may reach supernormal levels in patients with chronic psychoses.

  18. Increases in serum estrogen levels during major illness are caused by increased peripheral aromatization.

    PubMed

    Spratt, Daniel I; Morton, Jeremy R; Kramer, Robert S; Mayo, Sara W; Longcope, Christopher; Vary, Calvin P H

    2006-09-01

    Although serum testosterone levels decrease acutely in critically ill patients, estrogen levels rise. We hypothesized that increased rates of aromatization of androgens to estrogens underlie the increase in serum estrogen levels. Eleven men and three women (age 42-69 yr) were prospectively studied before and again after elective coronary artery bypass graft surgery (CABG). Each patient received priming doses of [(14)C]androgen and [(3)H]estrogen that were immediately followed by peripheral infusions for 210 min. Eight men and three women received androstenedione (A(4))/estrone (E(1)) and three men received testosterone (T)/estradiol (E(2)). Adipose tissue biopsies were obtained in another six men before and after CABG to evaluate levels of P450 aromatase mRNA. Serum T levels decreased postoperatively in all 17 men (P < 0.001), whereas E(1) levels rose (P = 0.004), with a trend toward a rise in E(2) (P = 0.23). Peripheral aromatization rates of androgens to estrogens rose markedly in all 14 patients (P < 0.0001). Estrogen clearance rates rose (P < 0.002). Mean serum A(4) levels increased slightly postoperatively (P = 0.04), although no increase in A(4) production rates (PRs) was observed. T PRs decreased in two of three men, whereas clearance rates increased in all three. Adipose tissue P450 aromatase mRNA content increased postoperatively (P < 0.001). We conclude that the primary cause of increased estrogen levels in acute illness is increased aromatase P450 gene expression, resulting in enhanced aromatization of androgens to estrogens, a previously undescribed endocrine response to acute illness. Both increased T clearance and decreased T production contribute to decreased serum T levels. Animal studies suggest that these opposing changes in circulating estrogen and androgen levels may be important to reduce morbidity and mortality in critical illness.

  19. Hyperglycemia may determine fibrinopeptide A plasma level increase in humans.

    PubMed

    Ceriello, A; Giugliano, D; Quatraro, A; Dello Russo, P; Marchi, E; Torella, R

    1989-12-01

    The effects of hyperglycemia on plasma fibrinopeptide A (FPA) levels in normal subjects are reported. An increase of FPA concentration parallel to sustained hyperglycemia was observed; when the glycemia returned to basal values, FPA showed values in normal range. Heparin infusion was able to significantly decrease the hyperglycemia-induced augment of FPA levels. Isovolumic-isotonic NaCl solution infusion produced a slight (NS) increase in FPA levels; however, mild hyperglycemia, achieved by glucagon, was also able to produce a significant increase in FPA concentration. These data demonstrate the direct role of hyperglycemia in conditioning FPA level, and suggest that hyperglycemia, by itself, is a sufficient stimulus to produce thrombin activation in humans.

  20. The effect of recombinant adeno-associated virus-adiponectin (rAAV2/1-Acrp30) on glycolipid dysmetabolism and liver morphology in diabetic rats.

    PubMed

    Long, Wen; Hui Ju, Zhong; Fan, Zhang; Jing, Wang; Qiong, Li

    2014-09-15

    Adiponectin is an adipocytokine derived from adipocytes with insulin resistance-improving and anti-inflammatory activities. The level of Adiponectin is decreased in obesity, insulin resistance and Type 2 diabetes mellitus. The administration of recombinant adiponectin has been shown to improve hyperglycemia and insulin resistance in diabetic mice. Therefore, we investigated the effects of recombinant adeno-associated virus-adiponectin (rAAV2/1-Acrp30) on the glycolipid profile and liver morphology in streptozotocin-induced diabetic rats. Animals were fed a high-fat/high-glucose diet for 4weeks and diabetes induced by intraperitoneal administration of streptozotocin. The animals were divided randomly into four groups: diabetes control group, rAAV2/1-Acrp30 treatment group, vacuity virus group, and normal control group. Compared with diabetic rats and those in the vacuity virus group, animals treated with rAAV2/1-Acrp30 exhibited significantly lower values for glycaemic and lipidic profiles, and significantly higher levels of HDL. Although APN expression increased in the liver tissue, serum levels were not significantly increased. However, the rAAV2/1-Acrp30 treated animals showed amelioration of hepatic disease, accompanied by marked reduction in the expression of NF-κBp65 and IκBα. The results suggest that rAAV2/1-Acrp30 ameliorates glycolipid dysmetabolism and hepatic disease in streptozotocin-induced diabetic rats. These observations indicate that the function of rAAV2/1-Acrp30 is mediated by downregulated expression of NF-κBp65 and IκBα.

  1. Circulating HMW adiponectin isoform is heritable and shares a common genetic background with insulin resistance in non diabetic White Caucasians from Italy: evidence from a family-based study

    PubMed Central

    Menzaghi, Claudia; Salvemini, Lucia; Paroni, Giulia; De Bonis, Concetta; Mangiacotti, Davide; Fini, Grazia; Doria, Alessandro; Di Paola, Rosa; Trischitta, Vincenzo

    2009-01-01

    Objective Reduced circulating adiponectin levels contribute to the etiology of insulin-resistance. Adiponectin circulates in three different isoforms: high (HMW), medium (MMW), and low (LMW) molecular weight. The genetics of adiponectin isoforms is mostly unknown. Our aim was to investigate whether and to which extent circulating adiponectin isoforms are heritable and whether they share common genetic backgrounds with insulin resistance-related traits. Methods In a family based sample of 640 non diabetic White Caucasians from Italy, serum adiponectin isoforms concentrations were measured by ELISA. Three SNPs in the ADIPOQ gene previously reported to affect total adiponectin levels (rs17300539, rs1501299 and rs677395) were genotyped. The heritability of adiponectin isoform levels was assessed by variance component analysis. A linear mixed effects model was used to test association between SNPs and adiponectin isoforms. Bivariate analyses were conducted to study genetic correlations between adiponectin isoforms levels and other insulin resistance-related traits. Results All isoforms were highly heritable (h2=0.60−0.80, p=1×10−13–1×10−23). SNPs rs17300539, rs1501299 and rs6773957 explained a significant proportion of HMW variance (2–9%, p=1×10−3–1×10−5). In a multiple-SNP model, only rs17300539 and rs1501299 remained associated with HMW adiponectin (p=3×10−4 and 2.0×10−2). Significant genetic correlations (p=1×10−2–1×10−5) were observed between HMW adiponectin and fasting insulin, HOMAIR, HDL-cholesterol and the metabolic syndrome score. Only rs1501299 partly accounted for these genetic correlations. Conclusion Circulating levels of adiponectin isoforms are highly heritable. The genetic control of HMW adiponectin is shared in part with insulin resistance-related traits and involves, but is not limited to the ADIPOQ locus. PMID:19761474

  2. 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

  3. Increased interleukin-13 levels in patients with chronic heart failure.

    PubMed

    Nishimura, Yuki; Inoue, Teruo; Nitto, Takeaki; Morooka, Toshifumi; Node, Koichi

    2009-01-24

    A great number of basic and clinical studies have demonstrated that inflammatory cytokines play an important role in development and progress of heart failure. However, there is limited information about allergic cytokine interleukin-13 (IL-13). The inflammatory responses mediated by allergic cytokines can cause significant morbidity and mortality when they become chronic. Therefore, we elucidated the role of IL-13 in the pathophysiology of chronic heart failure. We measured plasma IL-13 levels by enzyme-linked immunosorbent assay in 110 patients with chronic heart failure and 20 control subjects. Plasma IL-13 levels were increased in heart failure patients, compared with the controls, in association with NYHA functional class. In addition, IL-13 levels were correlated positively with plasma levels of brain natriuretic peptide and C-reactive protein, and negatively with left ventricular ejection fraction. Plasma IL-13 levels may be useful for evaluating disease severity in chronic heart failure.

  4. Globular adiponectin improves high glucose-suppressed endothelial progenitor cell function through endothelial nitric oxide synthase dependent mechanisms.

    PubMed

    Huang, Po-Hsun; Chen, Jia-Shiong; Tsai, Hsiao-Ya; Chen, Yung-Hsiang; Lin, Feng-Yen; Leu, Hsin-Bang; Wu, Tao-Cheng; Lin, Shing-Jong; Chen, Jaw-Wen

    2011-07-01

    Plasma levels of adiponectin, an adipose-specific protein with putative anti-atherogenic properties, could be down-regulated in obese and diabetic subjects. Recent insights suggest that the injured endothelial monolayer is regenerated by circulating endothelial progenitor cells (EPCs), but high glucose reduces number and functions of EPCs. Here, we tested the hypothesis that globular adiponectin can improve high glucose-suppressed EPC functions by restoration of endothelial nitric oxide synthase (eNOS) activity. Late EPCs isolated from healthy subjects appeared with cobblestone shape at 2-4 weeks. EPCs were incubated with high glucose (25 mM) and treatment with globular adiponectin for functional study. Migration and tube formation assays were used to evaluate the vasculogenetic capacity of EPCs. The activities of eNOS, Akt and concentrations of nitric oxide (NO) were also determined. Administration of globular adiponectin at physiological concentrations promoted EPC migration and tube formation, and dose-dependently upregulated phosphorylation of eNOS, Akt and augmented NO production. Chronic incubation of EPCs in high-glucose medium significantly impaired EPC function and induced cellular senescence, but these suppression effects were reversed by treatment with globular adiponectin. Globular adiponectin reversed high glucose-impaired EPC functions through NO- and p38 MAPK-related mechanisms. In addition, nude mice that received EPCs treated with adiponectin in high glucose medium showed a significant improvement in blood flow than those received normal saline and EPCs incubated in high glucose conditions. The administration of globular adiponectin improved high glucose-impaired EPC functions in vasculogenesis by restoration of eNOS activity. These beneficial effects may provide some novel rational to the vascular protective properties of adiponectin.

  5. Increased brain nitric oxide levels following ethanol administration.

    PubMed

    Finnerty, Niall; O'Riordan, Saidhbhe L; Klamer, Daniel; Lowry, John; Pålsson, Erik

    2015-05-01

    Nitric oxide is a ubiquitous messenger molecule, which at elevated concentrations has been implicated in the pathogenesis of several neurological disorders. Its role in oxidative stress, attributed in particular to the formation of peroxynitrite, proceeds through its high affinity for the superoxide radical. Alcoholism has recently been associated with the induction of oxidative stress, which is generally defined as a shift in equilibrium between pro-oxidant and anti-oxidant species in the direction of the former. Furthermore, its primary metabolite acetaldehyde, has been extensively associated with oxidative damage related toxic effects following alcohol ingestion. The principal objective of this study was the application of long term in vivo electrochemistry (LIVE) to investigate the effect of ethanol (0.125, 0.5 and 2.0 g kg(-1)) and acetaldehyde (12.5, 50 and 200 mg kg(-1)) on NO levels in the nucleus accumbens of freely moving rats. Systemic administrations of ethanol and acetaldehyde resulted in a dose-dependent increases in NO levels, albeit with very differing time courses. Subsequent to this the effect on accumbal NO levels, of subjecting the animal to different drug combinations, was also elucidated. The nitric oxide synthase inhibitor L-NAME (20 mg kg(-1)) and acetaldehyde sequestering agent D-penicillamine (50 mg kg(-1)) both attenuated the increase in NO levels following ethanol (1 g kg(-1)) administration. Conversely, the alcohol dehydrogenase inhibitor 4-methylpyrazole (25 mg kg(-1)) and catalase inhibitor sodium azide (10 mg kg(-1)) potentiated the increase in NO levels following ethanol administration. Finally, dual inhibition of aldehyde dehydrogenase and catalase by cyanamide (25 mg kg(-1)) caused an attenuation of ethanol effects on NO levels. Taken together these data highlight a robust increase in brain NO levels following systemic alcohol administration which is dependent on NO synthase activity and may involve both alcohol- and acetaldehyde

  6. Angiotensin-converting enzyme inhibitors improve hepatic steatosis by modulating expression of tumour necrosis factor-alpha, interleukin-6 and adiponectin receptor-2 in rats with type 2 diabetes.

    PubMed

    Zhang, Xia; Li, Zhong-Zhuan; Liu, Dong-Fang; Xu, Xin; Mei, Zhe-Chuan; Shen, Wei

    2009-07-01

    1. Angiotensin-converting enzyme inhibitors (ACEI) are hypotensive drugs that have been shown to prevent Type 2 diabetes mellitus (T2DM) in high-risk individuals. However, in T2DM, the effects of ACEI on hepatic steatosis are not known. The aim of the present study was to examine the effects of ACEI on changes in liver histology and hepatic mRNA expression of adipokines in rats with T2DM. 2. Thirty-six rats were divided into a normal control group, a T2DM group and a fosinopril-treated group. After six weeks of treatment with 5 mg/kg per day fosinopril, an ACEI, changes in liver histology, serum fasting glucose (FG), insulin, triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, adiponectin were evaluated, as was hepatic TNF-alpha, IL-6 and adiponectin receptor-2 (adipoR2) mRNA expression. 3. The degree of hepatic steatosis and inflammation, serum FG, insulin, TG, TC, ALT, TNF-alpha and IL-6 concentrations and hepatic TNF-alpha and IL-6 mRNA expression were significantly higher in rats with T2DM than in normal controls. Serum adiponectin concentrations and hepatic adipoR2 mRNA expression in rats with T2DM were significantly lower than in normal controls. Fosinopril significantly reduced the degree of hepatic steatosis, serum FG, insulin, ALT, TNF-alpha and IL-6 concentrations and hepatic TNF-alpha and IL-6 mRNA expression. Fosinopril significantly increased serum adiponectin concentrations and hepatic adipoR2 mRNA expression. 4. In conclusion, the ACEI improved insulin sensitivity and hepatic steatosis in rats with T2DM by increasing circulating adiponectin and hepatic adipoR2 levels, in addition to reducing pro-inflammatory cytokine levels in the circulation and liver.

  7. Increased isoprostane levels in oleic acid-induced lung injury

    SciTech Connect

    Ono, Koichi; Koizumi, Tomonobu; Tsushima, Kenji; Yoshikawa, Sumiko; Yokoyama, Toshiki; Nakagawa, Rikimaru; Obata, Toru

    2009-10-16

    The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2{alpha}). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.

  8. Reduced circulating oxytocin and High-Molecular-Weight adiponectin are risk factors for metabolic syndrome.

    PubMed

    Yuan, Guoyue; Qian, Weiyun; Pan, Ruirong; Jia, Jue; Jiang, Dan; Yang, Qichao; Wang, Su; Liu, Yuanxin; Yu, Shuqin; Hu, Hao; Sun, Wenjun; Ye, Jingjing; Mao, Chaoming; Zhuang, Ruo; Zhou, Libin

    2016-07-30

    The neurohypophysial hormone, oxytocin, is involved in the regulation of energy metabolism. Adiponectin (APN) is an adipose tissue-specific serum protein that inversely associates with metabolic syndrome (MetS). High-molecular-weight adiponectin (HMW APN) is considered the active form. In the present study, we aimed to determine the relationships of oxytocin and HMW APN to MetS and investigate whether or not the combination of oxytocin and HMW APN is associated with further metabolic abnormalities compared to each of them alone. A total of 170 subjects (75 with MetS and 95 non-MetS) were enrolled. Anthropometric parameters, oral glucose tolerance test (OGTT), blood lipids, hs-CRP, oxytocin and HMW APN levels were measured. Compared with non-MetS subjects, serum oxytocin and HMW APN levels were significantly lower in subjects with MetS (P<0.01). We then classified the subjects into three groups: high oxytocin and high HMW APN levels (high score group), low oxytocin and low HMW APN levels (low score group) and others. Participants in low score group showed the worst metabolic profiles and were more likely to have MetS compared to the other two group. In Spearman rank correlation coefficient, the classification by the combination of oxytocin and HMW APN was significantly correlated with a larger number of metabolic risk factors compared with classification by each of them alone. Individuals with low circulating oxytocin levels coupled with low HMW APN levels were at significantly increased risk of MetS. The combination of both markers would be useful for identifying MetS high risk patients.

  9. Inherent insulin sensitivity is a major determinant of multimeric adiponectin responsiveness to short-term weight loss in extreme obesity.

    PubMed

    Mai, Stefania; Walker, Gillian E; Brunani, Amelia; Guzzaloni, Gabriele; Grossi, Glenda; Oldani, Alberto; Aimaretti, Gianluca; Scacchi, Massimo; Marzullo, Paolo

    2014-07-24

    High molecular weight (HMW-A) adiponectin levels mirror alterations in glucose homeostasis better than medium (MMW-A) and low molecular weight (LMW-A) components. In 25 patients with wide-range extreme obesity (BMI 40-77 kg/m(2)), we aimed to explore if improvements of multimeric adiponectin following 4-wk weight loss reflect baseline OGTT-derived insulin sensitivity (ISIOGTT) and disposition index (DIOGTT). Compared to 40 lean controls, adiponectin oligomers were lower in extreme obesity (p < 0.001) and, within this group, HMW-A levels were higher in insulin-sensitive (p < 0.05) than -resistant patients. In obese patients, short-term weight loss did not change total adiponectin levels and insulin resistance, while the distribution pattern of adiponectin oligomers changed due to significant increment of HMW-A (p < 0.01) and reduction of MMW-A (p < 0.05). By multivariate analysis, final HMW-A levels were significantly related to baseline ISIOGTT and final body weight (adjusted R(2) = 0.41). Our data suggest that HMW adiponectin may reflect baseline insulin sensitivity appropriately in the context of extreme obesity. Especially, we documented that HMW-A is promptly responsive to short-term weight loss prior to changes in insulin resistance, by a magnitude that is proportioned to whole body insulin sensitivity. This may suggest an insulin sensitivity-dependent control operated by HMW-A on metabolic dynamics of patients with extreme obesity.

  10. Endozepine-4 levels are increased in hepatic coma

    PubMed Central

    Malaguarnera, Giulia; Vacante, Marco; Drago, Filippo; Bertino, Gaetano; Motta, Massimo; Giordano, Maria; Malaguarnera, Michele

    2015-01-01

    AIM: To evaluate the serum levels of endozepine-4, their relation with ammonia serum levels, the grading of coma and the severity of cirrhosis, in patients with hepatic coma. METHODS: In this study we included 20 subjects with Hepatic coma, 20 subjects with minimal hepatic encephalopathy (MHE) and 20 subjects control. All subjects underwent blood analysis, Child Pugh and Model for End - stage liver disease (MELD) assessment, endozepine-4 analysis. RESULTS: Subjects with hepatic coma showed significant difference in endozepine-4 (P < 0.001) and NH3 levels (P < 0.001) compared both to MHE and controls patients. Between NH3 and endozepine-4 we observed a significant correlation (P = 0.009; Pearson correlation 0.570). There was a significant correlation between endozepine-4 and MELD (P = 0.017; Pearson correlation = 0.529). In our study blood ammonia concentration was noted to be raised in patients with hepatic coma, with the highest ammonia levels being found in those who were comatose. We also found a high correlation between endozepine-4 and ammonia (P < 0.001). In patients with grade IV hepatic coma, endozepine levels were significantly higher compared to other groups. CONCLUSION: This study suggests that an increased level of endozepine in subjects with higher levels of MELD was observed. In conclusion, data concerning involvement of the GABA-ergic system in HE coma could be explained by stage-specific alterations. PMID:26290636

  11. Association of Single Nucleotide Polymorphisms of Adiponectin Gene with Type 2 Diabetes Mellitus, and Their Influence on Cardiovascular Risk Markers.

    PubMed

    Momin, A A; Bankar, M P; Bhoite, G M

    2017-03-01

    Type 2 diabetes mellitus is a genetically heterogeneous condition, characterized by insulin deficiency and/or insulin resistance. The etiology of type 2 diabetes is complex, with involvement of genetic and environmental factors. The adipose tissue protein 'adiponectin' is known to increase insulin sensitivity with decreased risk of type 2 diabetes mellitus. The gene for adiponectin is present on chromosome 3q27, the association of number of single nucleotide polymorphisms of adiponectin gene with type 2 diabetes and its complications have been reported. In the present study the two most common SNPs +45T/G & +276G/T, and their association with type 2 diabetes mellitus and cardiovascular markers were studied. The significant difference in genotype frequencies of +45T/G & +276G/T was found in type 2 diabetic patients and controls, with odds ratio of 1.13 & 1.26 respectively. BMI, Fasting blood glucose, fasting insulin, HOMA IR, triglyceride and VLDL cholesterol levels were increased, and HDL cholesterol level was decreased in patients carrier for +45T/G SNP than the wild type. While only decrease in the HDL cholesterol was reported in carriers for SNP +276G/T than the wild type. The logistic regression analysis revealed the positive association of SNP +45T/G with total cholesterol & LDL cholesterol. And negative association of HDL cholesterol was found with SNPs +45T/G and +276G/T. The haplotype analysis shows the alterations in means of biochemical markers in the patients having haplotype (GG) for mutant allele of SNP +45T/G and wild allele for SNP +276G/T.

  12. Increasing carbonmonoxide blood levels in Bangkok bus drivers

    SciTech Connect

    Saenghirunvattana, S.; Wananukul, W.; Mokkhavesa, C.; Opasi, N.

    1995-05-01

    In order to study the effects of air pollution in Bangkok, 31 bus drivers were examined and blood was drawn for measurement of carboxyhemoglobin (COHb) prior to and after work. The COHb level before work was 2.19{+-}2.46% (range 0.7.18). It had increased after work to 5.26{+-}2.52% (range 0-10.4) (p<0.001). Twenty-one drivers complained of chronic headaches, myalgia, and eye irritation during working hours. The COHb level was not statistically different between smokers and nonsmokers.

  13. The regulation of adiponectin receptors in human prostate cancer cell lines

    SciTech Connect

    Mistry, T.; Digby, J.E.; Chen, J.; Desai, K.M.; Randeva, H.S. . E-mail: H.Randeva@warwick.ac.uk

    2006-09-29

    Obesity is a risk factor for prostate cancer, and plasma levels of the adipokine, adiponectin, are low in the former but high in the latter. Adiponectin has been shown to modulate cell proliferation and apoptosis, suggesting that adiponectin and its receptors (Adipo-R1, Adipo-R2) may provide a molecular association between obesity and prostate carcinogenesis. We show for First time, the protein distribution of Adipo-R1 and Adipo-R2 in LNCaP and PC3 cells, and in human prostate tissue. Using real-time RT-PCR we provide novel data demonstrating the differential regulation of Adipo-R1 and Adipo-R2 mRNA expression by testosterone, 5-{alpha} dihydrotestosterone, {beta}-estradiol, tumour necrosis factor-{alpha}, leptin, and adiponectin in LNCaP and PC3 cells. Our findings suggest that adiponectin and its receptors may contribute to the molecular association between obesity and prostate cancer through a complex interaction with other hormones and cytokines that also play important roles in the pathophysiology of obesity and prostate cancer.

  14. Plasma Adiponectin Concentration and Its Association with Metabolic Syndrome in Patients with Heart Failure

    PubMed Central

    Won, Hoyoun; Shin, Min-Jeong; Oh, Jaewon; Hong, Namki; Park, Sungha; Lee, Sang-Hak; Jang, Yangsoo; Chung, Namsik

    2012-01-01

    Purpose Plasma adiponectin concentrations are inversely related with metabolic syndrome (MetS), and MetS is associated with increased risk for heart failure (HF). However, the relationship between adiponectin and MetS in HF remains undetermined. Therefore, we tested whether MetS was associated with the degree of plasma adiponectin concentrations in HF patients. Materials and Methods One hundred twenty eight ambulatory HF patients with left ventricular ejection fraction of <50% (80 males, 61.8±11.9 years old) were enrolled for this cross-sectional study. Echocardiographic measurements were performed, and plasma concentrations of adiponectin, lipoproteins, apolipoproteins (apoB, apoA1) and high sensitive C-reactive protein (hsCRP) were measured. Results Adiponectin concentrations in HF patients with MetS (n=43) were significantly lower than those without MetS (n=85) (9.7±7.0 vs. 15.8±10.9 µg/mL, p=0.001). Higher concentrations of apoB (p=0.017), apoB/A1 ratio (p<0.001), blood urea nitrogen (p=0.034), creatinine (p=0.003), and fasting insulin (p=0.004) were observed in HF patients with MetS compared with those without MetS. In HF patients with MetS, adiponectin concentrations were negatively correlated with hsCRP (r=-0.388, p=0.015) and positively correlated with the ratio of early mitral inflow velocity to early diastolic mitral annular velocity, E/E' (r=0.399, p=0.015). There was a significant trend towards decreased adiponectin concentrations with an increasing number of components of MetS (p for trend=0.012). Conclusion Our study demonstrated that adiponectin concentrations decreased in HF patients with MetS, and that relationship between adiponectin, inflammation and abnormal diastolic function, possibly leading to the progression of HF. PMID:22187237

  15. Methamphetamine increases basal ganglia iron to levels observed in aging.

    PubMed

    Melega, William P; Laćan, Goran; Harvey, Dennis C; Way, Baldwin M

    2007-10-29

    Increases in basal ganglia iron are well documented for neurodegenerative diseases but have not been associated with methamphetamine (METH). In this study, vervet monkeys that received two doses of METH (2 mg/kg, intramuscularly, 6 h apart) showed at 1 month, iron increases in substantia nigra pars reticulata and globus pallidus, with concurrent increases of ferritin-immunoreactivity and decreases of tyrosine hydroxylase-immunoreactivity in substantia nigra. At 1.5 years, substantia nigra tyrosine hydroxylase-immunoreactivity had recovered while iron and ferritin-immunoreactivity increases persisted. Globus pallidus and substantia nigra iron levels of the adult METH-exposed animals (age 5-9 years) were now comparable with those of drug-naive, aged animals (19-22 years), suggesting an aging-related condition that might render those regions more vulnerable to oxidative stress.

  16. Association of adiponectin and leptin with relative telomere length in seven independent cohorts including 11,448 participants.

    PubMed

    Broer, Linda; Raschenberger, Julia; Deelen, Joris; Mangino, Massimo; Codd, Veryan; Pietiläinen, Kirsi H; Albrecht, Eva; Amin, Najaf; Beekman, Marian; de Craen, Anton J M; Gieger, Christian; Haun, Margot; Henneman, Peter; Herder, Christian; Hovatta, Iiris; Laser, Annika; Kedenko, Lyudmyla; Koenig, Wolfgang; Kollerits, Barbara; Moilanen, Eeva; Oostra, Ben A; Paulweber, Bernhard; Quaye, Lydia; Rissanen, Aila; Roden, Michael; Surakka, Ida; Valdes, Ana M; Vuolteenaho, Katriina; Thorand, Barbara; van Dijk, Ko Willems; Kaprio, Jaakko; Spector, Tim D; Slagboom, P Eline; Samani, Nilesh J; Kronenberg, Florian; van Duijn, Cornelia M; Ladwig, Karl-Heinz

    2014-09-01

    Oxidative stress and inflammation are major contributors to accelerated age-related relative telomere length (RTL) shortening. Both conditions are strongly linked to leptin and adiponectin, the most prominent adipocyte-derived protein hormones. As high leptin levels and low levels of adiponectin have been implicated in inflammation, one expects adiponectin to be positively associated with RTL while leptin should be negatively associated. Within the ENGAGE consortium, we investigated the association of RTL with adiponectin and leptin in seven independent cohorts with a total of 11,448 participants. We performed partial correlation analysis on Z-transformed RTL and LN-transformed leptin/adiponectin, adjusting for age and sex. In extended models we adjusted for body mass index (BMI) and C-reactive protein (CRP). Adiponectin showed a borderline significant association with RTL. This appeared to be determined by a single study and when the outlier study was removed, this association disappeared. The association between RTL and leptin was highly significant (r = -0.05; p = 1.81 × 10(-7)). Additional adjustment for BMI or CRP did not change the results. Sex-stratified analysis revealed no difference between men and women. Our study suggests that high leptin levels are associated with short RTL.

  17. B-type natriuretic peptide and adiponectin releases in rat model of myocardial damage induced by isoproterenol administration

    PubMed Central

    Hasić, Sabaheta; Hadžović-Džuvo, Almira; Jadrić, Radivoj; Kiseljaković, Emina

    2013-01-01

    B-type natriuretic peptide (BNP) and adiponectin play important role in the cardiovascular homeostasis regulation. We investigated BNP and adiponectin serum levels followed by isoproterenol (ISO) administration to rats and explored the relationship between them. Cardiac troponin I (cTnI) blood level was used as biochemical evidence of myocardial damage development. Adult male Wistar rats (average body weight 273.33±21.63 g) were distributed into groups: control group received saline (n=6) and ISO groups (n=12) treated with ISO (subcutaneous single dose 100 mg/kg of rat body weight). ISO group was divided into two groups according to the time of BNP, adiponectin and cTnI determination: ISO I (n=6; 2 hours after ISO administration); ISO II (n=6; 4 hours after ISO administration). Blood for determination of parameters was taken from rat abdominal aorta. BNP, adiponectin and cTnI were determined by ELISA method. Data were statistically analysed by using SPSS version13 computer program. P value less 0.05 was considered statistically significant. Blood BNP and adiponectin were lower at 2 hours after ISO administration in comparison with control group (p=0.004 for BNP and p=0.174 for adiponectin). Four hours after ISO administration, we have noted significant elevation of both parameters compared to ISO I group (p=0.004 for BNP;p=0.02 for adiponectin). Test of correlation have showed significant relation between their blood levels during experimental period (rho=0.577; p=0.01). BNP and adiponectin are not simple indicators of myocardial damage development. They have possible associated and additive effects in cardiovascular homeostasis regulation. PMID:24289757

  18. A Mutant of Arabidopsis with Increased Levels of Stearic Acid.

    PubMed Central

    Lightner, J.; Wu, J.; Browse, J.

    1994-01-01

    A mutation at the fab2 locus of Arabidopsis caused increased levels of stearate in leaves. The increase in leaf stearate in fab2 varied developmentally, and the largest increase occurred in young leaves, where stearate accounted for almost 20% of total leaf fatty acids. The fatty acid composition of leaf lipids isolated from the fab2 mutant showed increased stearate in all the major glycerolipids of both the chloroplast and extrachloroplast membranes. Although the stearate content was increased, the fab2 mutant still contained abundant amounts of 18:1, 18:2, and 18:3 fatty acids. These results are consistent with the expectations for a mutation partially affecting the action of the stromal stearoyl-acyl carrier protein desaturase. Positional analysis indicated that the extra 18:0 is excluded with high specificity from the sn-2 position of both chloroplast and extrachloroplast glycerolipids. Although stearate content was increased in all the major leaf membrane lipids, the amount of increase varied considerably among the different lipids, from a high of 25% of fatty acids in phosphatidylcholine to a low of 2.9% of fatty acids in monogalactosyldiacylglycerol. PMID:12232421

  19. Excess nicotinamide increases plasma serotonin and histamine levels.

    PubMed

    Tian, Yan-Jie; Li, Da; Ma, Qiang; Gu, Xin-Yi; Guo, Ming; Lun, Yong-Zhi; Sun, Wu-Ping; Wang, Xin-Yuan; Cao, Yu; Zhou, Shi-Sheng

    2013-02-25

    Methylation, a methyl group-consuming reaction, plays a key role in the degradation (i.e., inactivation) of monoamine neurotransmitters, including catecholamines, serotonin and histamine. Without labile methyl groups, the methylation-mediated degradation cannot take place. Although high niacin (nicotinic acid and nicotinamide) intake, which is very common nowadays, is known to deplete the body's methyl-group pool, its effect on monoamine-neurotransmitter degradation is not well understood. The aim of this article was to investigate the effect of excess nicotinamide on the levels of plasma serotonin and histamine in healthy subjects. Urine and venous blood samples were collected from nine healthy male volunteers before and after oral loading with 100 mg nicotinamide. Plasma N(1)-methylnicotinamide, urinary N(1)-methyl-2-pyridone-5-carboxamide (2-Py), and plasma betaine levels were measured by using high-performance liquid chromatography (HPLC). Plasma concentrations of choline, serotonin and histamine were measured using commercial kits. The results showed that the plasma N(1)-methylnicotinamide level and the urinary excretion of 2-Py significantly increased after oral loading with 100 mg nicotinamide, which was accompanied with a decrease in the methyl-group donor betaine. Compared with those before nicotinamide load, five-hour postload plasma serotonin and histamine levels significantly increased. These results suggest that excess nicotinamide can disturb monoamine-neurotransmitter metabolism. These findings may be of significance in understanding the etiology of monoamine-related mental diseases, such as schizophrenia and autism (a neurodevelopmental disorder).

  20. Aspergillus fumigatus challenge increases cytokine levels in nasal lavage fluid.

    PubMed

    Stark, H; Roponen, M; Purokivi, M; Randell, J; Tukiainen, H; Hirvonen, M-R

    2006-12-01

    Several studies have shown an association between exposure in moisture-damaged buildings and adverse health effects. There are several indicator microbes of moisture damage, but Aspergillus fumigatus is one of the best-documented molds provoking health problems in different occupational conditions. We assessed whether inhalation of a commercial A. fumigatus solution would affect cytokine levels (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-4, IL-6, interferon [IFN]-gamma) in nasal lavage fluid (NAL) compared with that evoked by placebo challenge. Twenty-seven subjects were studied: 13 had occupational exposure in a moisture-damaged building, 4 were atopic, and 10 were considered as controls. In all the subjects, the IL-1beta levels were increased significantly both at 6 (p = 0.013) and 24 h (p = .005) after the A. fumigatus challenge compared to placebo. In subjects with previous occupational exposure in a moisture-damaged building, IL-4 concentrations were increased significantly both at 6 (p =.046) and 24 h (p =.008) after the A. fumigatus challenge compared with placebo. Furthermore, in the control group, TNF-alpha levels were significantly increased at 6 h after the A. fumigatus challenge compared to placebo (p = .028). Thus, these data show a link between markers of inflammation in NAL and experimental A. fumigatus challenge.

  1. 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

    SciTech Connect

    Chang, Young-Chae; Cho, Hyun-Ji

    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, without 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.

  2. LOW 24-HOUR ADIPONECTIN AND HIGH NOCTURNAL LEPTIN CONCENTRATIONS IN A CASE CONTROL STUDY OF COMMUNITY-DWELLING PREMENOPAUSAL WOMEN WITH MAJOR DEPRESSION The P.O.W.E.R. Study

    PubMed Central

    Cizza, Giovanni; Nguyen, Vi T.; Eskandari, Farideh; Duan, Zhigang; Wright, Elizabeth C.; Reynolds, James C.; Ahima, Rexford S.; Blackman, Marc R.

    2012-01-01

    Objective Major depressive disorder (MDD) is associated with immune system dysfunction and disruption of multiple circadian systems. Adiponectin is an adipocytokine with anti-inflammatory and anti-atherogenic effects. Circulating concentrations are inversely related to adiposity and risks of metabolic syndrome and diabetes mellitus. Our goals were to: A) establish whether premenopausal women with MDD exhibit decreased plasma adiponectin concentrations and/or disruption of circadian adiponectin rhythmicity; B) assess whether there is a relationship between adiponectin and MDD; C) explore the temporal relationships among adiponectin, leptin, ACTH and cortisol secretion. Method Case-control study of community-dwelling premenopausal women with MDD and age- and BMI-matched-control subjects (N=23/group). Main outcome measures were circulating concentrations of adiponectin, leptin, ACTH, and cortisol measured hourly for 24h. Results Women with MDD had approximately 30% lower mean 24h concentrations of adiponectin than did control subjects. Adiponectin was inversely related to depression severity and total duration of disease, suggesting a causal link. In contrast, nocturnal leptin concentrations were higher in the MDD versus control groups. Leptin was inversely related to cortisol and adiponectin both in subjects with depression and in control subjects. In cross-correlation analyses, the relationship between ACTH and cortisol was stronger in women with MDD than in control subjects, consistent with HPA-axis activation in MDD. Conclusions Reduced daily adiponectin production may increase the risk of diabetes mellitus, and elevated leptin may contribute to osteoporosis, in premenopausal women with MDD. PMID:20492842

  3. Decreased training volume and increased carbohydrate intake increases oxidized LDL levels.

    PubMed

    Välimäki, I A; Vuorimaa, T; Ahotupa, M; Kekkonen, R; Korpela, R; Vasankari, T

    2012-04-01

    We studied effects of probiotics and training volume on oxidized LDL lipids (ox-LDL), serum antioxidant potential (s-TRAP) and serum antioxidants (s-α-tocopherol, s-γ-tocopherol, s-retinol, s-β-carotene and s-ubiquinone-10) in marathon runners during 3-months training period, 6-days preparation period and marathon run. Runners (n=127) were recruited for a randomized, double-blind intervention during which they received either Lactobacillus rhamnosus GG (LGG, probiotic group) or placebo drink (placebo group) during whole study. During the preparation period, subjects decreased training and increased carbohydrate intake. Blood samples were taken at baseline, before 6-days preparation, before and immediately after the marathon. Probiotics did not have any effect on ox-LDL, s-TRAP or serum antioxidants levels during the study. Interestingly, ox-LDL increased by 28% and 33% during the preparation period and decreased by 16% and 19% during the marathon run in the placebo and probiotic groups, respectively (in all, P<0.001). No changes were seen in s-TRAP before marathon, but during run s-TRAP raised by 16% in both groups (both, P<0.001). The increase of ox-LDL level during the preparative period after several months' training suggests that aerobic training may reduce the concentration of ox-LDL and that decrease of training together with increased energy intake, mainly carbohydrate, before marathon is capable of increasing the level of ox-LDL.

  4. Hydrocellular foam dressing increases the leptin level in wound fluid.

    PubMed

    Yoshino, Sawako; Nakagami, Gojiro; Ohira, Tomomi; Kawasaki, Rui; Shimura, Mari; Iwatsuki, Ken; Sanada, Hiromi; Kobayashi-Hattori, Kazuo; Oishi, Yuichi; Yamane, Takumi

    2015-09-01

    Hydrocellular foam dressing (HCF) absorbs excessive wound fluid, which contains various cytokines and growth factors, and ensures a moist environment to promote wound healing. However, the molecular mechanisms underlying the wound fluid component changes induced by HCF are poorly understood. In the present study, we examined the effect of HCF on wound healing and the associated regulatory mechanisms in relation to variations in cytokine levels in the wound fluid. We created full-thickness wounds on the dorsolateral skin of rats and collected the resulting wound fluid samples. HCF was immersed in a plate containing the wound fluids. HCF was then removed and the excess wound fluid remaining in the plate was examined by cytokine array and enzyme-linked immunosorbent assay. We also used a rat model and human dermal fibroblast cultures to examine the effect of wound fluid component changes during the wound healing process. Upon treatment with HCF, leptin levels were upregulated in the wound fluid. Fibroblast proliferation was enhanced and the effect was suppressed in the presence of leptin antagonist. In our in vivo model, HCF increased wound contraction compared with film dressings and this positive effect of HCF was suppressed by addition of leptin antagonist. Our results suggest that dermal fibroblast proliferation is upregulated by HCF due to increased leptin level at the wound surface, and these effects promote wound healing. We believe that the present study contributes to furthering the understanding of the mechanisms underlying the effects of HCF-induced wound healing.

  5. Myeloid Cell-Specific Lipin-1 Deficiency Stimulates Endocrine Adiponectin-FGF15 Axis and Ameliorates Ethanol-Induced Liver Injury in Mice

    PubMed Central

    Wang, Jiayou; Kim, Chunki; Jogasuria, Alvin; Han, Yoonhee; Hu, Xudong; Wu, Jiashin; Shen, Hong; Chrast, Roman; Finck, Brian N.; You, Min

    2016-01-01

    Lipin-1 is a phosphatidate phosphohydrolase (PAP) required for the generation of diacylglycerol during glycerolipid synthesis, and exhibits dual functions in the regulation of lipid metabolism. Lipin-1 has been implicated in the pathogenesis of alcoholic liver disease (ALD). In the present study, we assessed lipin-1 function in myeloid cells in ALD using a myeloid cell-specific lipin-1 knockout (mLipin-1KO) mouse model. Utilizing the Gao-binge ethanol feeding protocol, matched mLipin-1KO mice and littermate loxP control (WT) mice were pair-fed with either an ethanol-containing diet or an ethanol-free diet (control). Surprisingly, deletion of lipin-1 in myeloid cells dramatically attenuated liver inflammatory responses and ameliorated liver injury that would normally occur following the ethanol feeding protocol, but slightly exacerbated the ethanol-induced steatosis in mice. Mechanistically, myeloid cell-specific lipin-1 deficiency concomitantly increased the fat-derived adiponectin and ileum-derived fibroblast growth factor (FGF) 15. In concordance with concerted elevation of circulating adiponectin and FGF15, myeloid cell-specific lipin-1 deficiency diminished hepatic nuclear factor kappa B (NF-κB) activity, limited liver inflammatory responses, normalized serum levels of bile acids, and protected mice from liver damage after ethanol challenge. Our novel data demonstrate that myeloid cell-specific deletion of lipin-1 ameliorated inflammation and alcoholic hepatitis in mice via activation of endocrine adiponectin-FGF15 signaling. PMID:27666676

  6. Increased endogenous DNA oxidation correlates to increased iron levels in melanocytes relative to keratinocytes.

    PubMed

    Pelle, Edward; Huang, Xi; Zhang, Qi; Pernodet, Nadine; Yarosh, Daniel B; Frenkel, Krystyna

    2014-01-01

    The endogenous oxidative state of normal human epidermal melanocytes was investigated and compared to normal human epidermal keratinocytes (NHEKs) in order to gain new insight into melanocyte biology. Previously, we showed that NHEKs contain higher levels of hydrogen peroxide (H2O2) than melanocytes and that it can migrate from NHEKs to melanocytes by passive permeation. Nevertheless, despite lower concentrations of H2O2, we now report higher levels of oxidative DNA in melanocytes as indicated by increased levels of 8-oxo-2'-deoxyguanosine (8-oxo-dG): 4.49 (±0.55 SEM) 8-oxo-dG/10(6) dG compared to 1.49 (±0.11 SEM) 8-oxo-dG/10(6) dG for NHEKs. An antioxidant biomarker, glutathione (GSH), was also lower in melanocytes (3.14 nmoles (±0.15 SEM)/cell) in comparison to NHEKs (5.98 nmoles (±0.33 SEM)/cell). Intriguingly, cellular bioavailable iron as measured in ferritin was found to be nearly fourfold higher in melanocytes than in NHEKs. Further, ferritin levels in melanocytes were also higher than in hepatocarcinoma cells, an iron-rich cell, and it indicates that higher relative iron levels may be characteristic of melanocytes. To account for the increased oxidative DNA and lower GSH and H2O2 levels that we observe, we propose that iron may contribute to higher levels of oxidation by reacting with H2O2 through a Fenton reaction leading to the generation of DNA-reactive hydroxyl radicals. In conclusion, our data support the concept of elevated oxidation and high iron levels as normal parameters of melanocytic activity. We present new evidence that may contribute to our understanding of the melanogenic process and lead to the development of new skin care products.

  7. Groundwater depletion's contribution to sea level rise increasing

    NASA Astrophysics Data System (ADS)

    Schultz, Colin

    2011-11-01

    Since the turn of the twentieth century, industrial-scale redistribution of water from landlocked aquifers to the ocean has driven up the global average sea level by more than 12 centimeters. Between 1900 and 2008, roughly 4500 cubic kilometers of water was drawn from the ground, largely to feed an agricultural system increasingly reliant on irrigation. Of that 4500-cubic-kilometer total (nearly the volume of Lake Michigan), 1100 cubic kilometers were pumped out between 2000 and 2008 alone. This early-21st-century groundwater depletion was responsible for raising global sea level at a rate of 0.4 millimeter per year, an eighth of the observed total. These updated values, falling near the middle of the range of previous estimates, are the product of an investigation by Konikow that drew together a variety of volumetric measurements of groundwater storage.

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

    SciTech Connect

    Kuroyanagi, Kayo; Kang, Min-Sook; Goto, Tsuyoshi; Hirai, Shizuka; Ohyama, Kana; Kusudo, Tatsuya; Yu, Rina; Yano, Masamichi; Sasaki, Takao; Takahashi, Nobuyuki; Kawada, Teruo

    2008-02-01

    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 and suggest that the consumption of citrus fruits, which contain auraptene can lead to a partial prevention of lipid and glucose metabolism abnormalities.

  9. Increased copeptin levels in metabolic syndrome from a Romanian population

    PubMed Central

    Vintilă, M; Gheorghiu, ML; Caragheorgheopol, A; Baculescu, N; Lichiardopol, C; Badiu, C; Coculescu, M; Grigorescu, F; Poiană, C

    2016-01-01

    Rationale: Arginine vasopressin (AVP) is secreted under conditions of water deprivation. Since AVP has a low half-life in the plasma, the C-terminal fragment of AVP-precursor (copeptin) was used to estimate the AVP levels. High copeptin levels increase the risk for the development of diabetes mellitus. Aim: This study was aimed to measure copeptin levels in the metabolic syndrome (MetS) in Romanians using a competitive enzyme immunoassay. Methods and results: Patients prone to present MetS (n = 63) were compared to controls (n = 42). In the MetS group, the syndrome was confirmed in 93.6%. Affected patients displayed 85.7% obesity and insulin resistance (HOMAIR of 4.9 ± 0.4 versus 1.1 ± 0.8 in controls). Low HDL-cholesterol was less represented (47.5%). Copeptin levels were 0.6 ± 0.0 in MetS versus 0.42 ± 0.0 ng/ mL in controls (P < 0.004). Higher copeptin (0.79 to 1.83 ng/ mL) was associated with MetS, P < 0.0018, OR 20, 95%CI [3.03 – 131.7]. In ANOVA, high copeptin was equally explained by MetS or obesity (P < 0.05,α = 3.8). The best correlation was found with high triglyceride levels (P < 0.013,α = 6.3) while the correlation with HOMAIR remained not significant. Discussion: These data indicated a concordant correlation between increased copeptin and MetS or its components. In the light of epidemiological data, indicating that more than 50% of the European population has a lower daily water intake and a fraction of 25% displaying high copeptin, our data further sustained that copeptin may be a good biomarker for MetS and/ or obesity, which should be further investigated with other members of the osmoregulation pathway at both pathogenesis and genetic levels. PMID:27928437

  10. Transgenic cells with increased plastoquinone levels and methods of use

    SciTech Connect

    Sayre, Richard T.; Subramanian, Sowmya; Cahoon, Edgar

    2016-12-27

    Disclosed herein are transgenic cells expressing a heterologous nucleic acid encoding a prephenate dehydrogenase (PDH) protein, a heterologous nucleic acid encoding a homogentisate solanesyl transferase (HST) protein, a heterologous nucleic acid encoding a deoxyxylulose phosphate synthase (DXS) protein, or a combination of two or more thereof. In particular examples, the disclosed transgenic cells have increased plastoquinone levels. Also disclosed are methods of increasing cell growth rates or production of biomass by cultivating transgenic cells expressing a heterologous nucleic acid encoding a PDH protein, a heterologous nucleic acid encoding an HST protein, a heterologous nucleic acid encoding a DXS protein, or a combination of two or more thereof under conditions sufficient to produce cell growth or biomass.

  11. Acute stress induces increases in salivary IL-10 levels.

    PubMed

    Szabo, Yvette Z; Newton, Tamara L; Miller, James J; Lyle, Keith B; Fernandez-Botran, Rafael

    2016-09-01

    The purpose of this study was to investigate the stress-reactivity of the anti-inflammatory cytokine, IL-10, in saliva and to determine how salivary IL-10 levels change in relation to those of IL-1β, a pro-inflammatory cytokine, following stress. Healthy young adults were randomly assigned to retrieve a negative emotional memory (n = 46) or complete a modified version of the Trier Social Stress Test (n = 45). Saliva samples were taken 10 min before (baseline) and 50 min after (post-stressor) onset of a 10-min stressor, and were assayed using a high sensitivity multiplex assay for cytokines. Measurable IL-10 levels (above the minimum detectable concentration) were found in 96% of the baseline samples, and 98% of the post-stressor samples. Flow rate-adjusted salivary IL-10 levels as well as IL-1β/IL-10 ratios showed moderate but statistically significant increases in response to stress. Measurement of salivary IL-10 and pro-/anti-inflammatory cytokine ratios may be useful, noninvasive tools, in stress research.

  12. [Adiponectin: an anti-carcinogenic adipokine?].

    PubMed

    Fève, Bruno

    2013-05-01

    Adipose tissue has long been considered as an « organ » of energy storage. Although many works had previously identified the secretory nature of adipocyte, it was only in 1994, when the leptin gene was cloned, that adipose tissue earned the status of endocrine tissue. It was the first demonstration that an adipose tissue-derived hormone was able to communicate with the central nervous system to control satiety and energy balance. In fact, it is almost at the same time that another major adipokine produced by adipocytes, adiponectin, has been discovered. It took several years to identify the insulin-sensitizing, anti-inflammatory and anti-atherogenic properties of this hormone. More recently, several epidemiological, genetic and experimental findings suggest an anti-carcinogenic role for adiponectin. In this brief review we will present the arguments supporting a protective role of adiponectin in tumor progression, particularly in the context of breast cancer. Adiponectin deficiency commonly observed in obesity may contribute to the natural history of several cancers, as well as the elevation of leptin and other hormonal disturbances associated with excessive adiposity.

  13. 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

  14. Construction of adiponectin-encoding plasmid DNA and overexpression in mice in vivo.

    PubMed

    Huang, Yan-Na; Qi, Jian-Hua; Xiang, Lan; Wang, Yi-Zhen

    2012-07-10

    The effects of elevated adiponectin (ADN) plasma levels on food intake, body weight, and lipid deposition of wild-type mice through ADN gene transfer using hydrodynamic based-gene delivery (HD) were investigated. The administration of pTarget/ADN significantly increased the blood ADN levels on days 1, 3, and 7 as well as food intake and body weight. Reverse transcription polymerase chain reaction (RT-PCR) was used to investigate the key-function genes involved in lipid deposition on epididymal fat, gastrocnemius, and extensor digitorum longus on days 1 and 7. The amounts of adipose triglyceride lipase, hormone-sensitive lipase, and lipoprotein lipase mRNA in the three samples significantly increased. We determined sirtuin 1 (SIRT1), forkhead box O3 (FOXO3a), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) gene expression and protein level in these samples. The amounts of SIRT1, FOXO3a, and PGC-1α mRNA in epididymal fat, gastrocnemius, and extensor digitorum longus remarkably increased. However, a significant increase in SIRT1 and PGC-1α protein levels was only observed in extensor digitorum longus. These results suggest that high doses of ADN can increase food intake and body weight. Elevated ADN levels may also affect fat deposition on the adipose tissue and skeletal muscles of wild-type mice via SIRT1, FOXO3a, and its downstream targets, including PGC-1α.

  15. Globular adiponectin inhibits ethanol-induced apoptosis in HepG2 cells through heme oxygenase-1 induction.

    PubMed

    Nepal, Saroj; Kim, Mi Jin; Subedi, Amit; Lee, Eung-Seok; Yong, Chul Soon; Kim, Jung-Ae; Kang, WonKu; Kwak, Mi-Kyung; Arya, Dharamvir Singh; Park, Pil-Hoon

    2012-10-01

    Hepatocellular apoptosis is an essential pathological feature of alcoholic liver disease. Adiponectin, an adipokine predominantly secreted from adipose tissue, has been shown to play beneficial roles in alcoholic liver disease against various inflammatory and pro-apoptotic molecules. However, the effects of adiponectin on ethanol-induced apoptosis in liver cells are largely unknown. Herein, we investigated the role of globular adiponectin (gAcrp) in the prevention of ethanol-induced apoptosis and further tried to decipher the potential mechanisms involved. In the present study, we demonstrated that gAcrp significantly inhibits both ethanol-induced increase in Fas ligand expression and activation of caspase-3 in human hepatoma cell lines (HepG2 cells), suggesting that gAcrp plays a protective role against ethanol-induced apoptosis in liver cells. This protective effect of gAcrp was mediated through adiponectin receptor R1 (adipoR1). Further, globular adiponectin treatment caused induction of heme oxygenase-1 (HO-1) through, at least in part, nuclear factor (erythroid-derived 2)-like 2, (Nrf2) signaling. Treatment with SnPP, a pharmacological inhibitor of HO-1, and knockdown of HO-1 with small interfering RNA (siRNA) restored caspase-3 activity suppressed by gAcrp, indicating a critical role of HO-1 in mediating the protective role of gAcrp in ethanol-induced apoptosis in liver cells. In addition, carbon monoxide, a byproduct obtained from the catabolism of free heme was found to contribute to the anti-apoptotic effect of adiponectin. In conclusion, these data demonstrated that globular adiponectin prevents ethanol-induced apoptosis in HepG2 cells via HO-1 induction and revealed a novel biological response of globular adiponectin in the protection of liver injury from alcohol consumption.

  16. Gender differences in the association of visceral and subcutaneous adiposity with adiponectin in African Americans: the Jackson Heart Study

    PubMed Central

    2013-01-01

    Background Adiponectin, paradoxically reduced in obesity and with lower levels in African Americans (AA), modulates several cardiometabolic risk factors. Because abdominal visceral adipose tissue (VAT), known to be reduced in AA, and subcutaneous adipose tissue (SAT) compartments may confer differential metabolic risk profiles, we investigated the associations of VAT and SAT with serum adiponectin, separately by gender, with the hypothesis that VAT is more strongly inversely associated with adiponectin than SAT. Methods Participants from the Jackson Heart Study, an ongoing cohort of AA (n = 2,799; 64% women; mean age, 55 ± 11 years) underwent computer tomography assessment of SAT and VAT volumes, and had stored serum specimens analyzed for adiponectin levels. These levels were examined by gender in relation to increments of VAT and SAT. Results Compared to women, men had significantly lower mean levels of adiponectin (3.9 ± 3.0 μg/mL vs. 6.0 ± 4.4 μg/mL; p < 0.01) and mean volume of SAT (1,721 ± 803 cm3 vs. 2,668 ± 968 cm3; p < 0.01) but significantly higher mean volume of VAT (884 ± 416 cm3 vs. 801 ± 363 cm3; p < 0.01). Among women, a one standard deviation increment in VAT was inversely associated with adiponectin (β = − 0.13; p < 0.0001) after controlling for age, systolic blood pressure, fasting plasma glucose, high-density lipoprotein cholesterol, triglycerides, education, pack-years of smoking and daily intake of alcohol. The statistically significant inverse association of VAT and adiponectin persisted after additionally adjusting for SAT, body mass index (BMI) and waist circumference (WC), suggesting that VAT provides significant information above and beyond BMI and WC. Among men, after the same multivariable adjustment, there was a direct association of SAT and adiponectin (β = 0.18; p = 0.002) that persisted when controlling for BMI and WC, supporting a beneficial effect of

  17. Phytoplankton succession during acidification with and without increasing aluminum levels.

    PubMed

    Havens, K E; Heath, R T

    1990-01-01

    An in situ mesocosm experiment was performed to investigate the role of aluminum in controlling phytoplankton community succession during lake acidification. Large (2000 liter) mesocosms were suspended in mesotrophic East Twin Lake, Ohio, USA. Duplicates were either untreated controls (pH 8.8), acidified to pH 4.5 over 23 days, or acidified and spiked with 200 microg/liter Al in incremental additions. Filamentous blue greens, diatoms and other chrysophytes became extinct in both acid treatments, but declined most rapidly where Al levels were also increased. The large desmid Closterium and the filamentous chlorophyte Mougoetia became dominant in the Acid treatment. In the Acid + Al treatment, these algae also became dominant, but the species with greatest biomass was the dinoflagellate Peridinium inconspicuum. Acidification (with or without added Al) also resulted in a significant shift in the algal size spectrum to larger (> 20 microm) cells.

  18. Increased levels of sister chromatid exchanges in military aircraft pilots.

    PubMed

    Silva, M J; Carothers, A; Castelo Branco, N; Dias, A; Boavida, M G

    1999-04-26

    Sister chromatid exchanges (SCEs) were scored in lymphocytes of nine high-performance pilots of alphajet aircrafts and of ten control individuals from the same air base. Statistical analysis of the mean SCE count per cell in the total number of cells analyzed as well as in those having 12 or more SCEs (high-frequency cells, HFCs) revealed a significant difference between pilots and controls, after adjusting for the effect of smoking. Analysis of the cell cycle kinetic data (replication and mitotic indices) revealed no significant differences either between pilots and controls or between smokers and nonsmokers. Previously, we reported an increase in the SCE levels in workers of the aeronautical industry exposed to noise and whole-body vibration. The present results corroborate those findings and indicate that noise and whole-body vibration may cause genotoxic effects in man.

  19. Artificially Increased Yolk Hormone Levels and Neophobia in Domestic Chicks

    PubMed Central

    Bertin, Aline; Arnould, Cécile; Moussu, Chantal; Meurisse, Maryse; Constantin, Paul; Leterrier, Christine; Calandreau, Ludovic

    2015-01-01

    In birds there is compelling evidence that the development and expression of behavior is affected by maternal factors, particularly via variation in yolk hormone concentrations of maternal origin. In the present study we tested whether variation in yolk hormone levels lead to variation in the expression of neophobia in young domestic chicks. Understanding how the prenatal environment could predispose chicks to express fear-related behaviors is essential in order to propose preventive actions and improve animal welfare. We simulated the consequences of a maternal stress by experimentally enhancing yolk progesterone, testosterone and estradiol concentrations in hen eggs prior to incubation. The chicks from these hormone-treated eggs (H) and from sham embryos (C) that received the vehicle-only were exposed to novel food, novel object and novel environment tests. H chicks approached a novel object significantly faster and were significantly more active in a novel environment than controls, suggesting less fearfulness. Conversely, no effect of the treatment was found in food neophobia tests. Our study highlights a developmental influence of yolk hormones on a specific aspect of neophobia. The results suggest that increased yolk hormone levels modulate specifically the probability of exploring novel environments or novel objects in the environment. PMID:26633522

  20. Towards engineering increased pantothenate (vitamin B(5)) levels in plants.

    PubMed

    Chakauya, Ereck; Coxon, Katy M; Wei, Ma; Macdonald, Mary V; Barsby, Tina; Abell, Chris; Smith, Alison G

    2008-11-01

    Pantothenate (vitamin B(5)) is the precursor of the 4'-phosphopantetheine moiety of coenzyme A and acyl-carrier protein. It is made by plants and microorganisms de novo, but is a dietary requirement for animals. The pantothenate biosynthetic pathway is well-established in bacteria, comprising four enzymic reactions catalysed by ketopantoate hydroxymethyltransferase (KPHMT), L: -aspartate-alpha-decarboxylase (ADC), pantothenate synthetase (PS) and ketopantoate reductase (KPR) encoded by panB, panD, panC and panE genes, respectively. In higher plants, the genes encoding the first (KPHMT) and last (PS) enzymes have been identified and characterised in several plant species. Commercially, pantothenate is chemically synthesised and used in vitamin supplements, feed additives and cosmetics. Biotransformation is an attractive alternative production system that would circumvent the expensive procedures of separating racemic intermediates. We explored the possibility of manipulating pantothenate biosynthesis in plants. Transgenic oilseed rape (Brassica napus) lines were generated in which the E. coli KPHMT and PS genes were expressed under a strong constitutive CaMV35SS promoter. No significant change of pantothenate levels in PS transgenic lines was observed. In contrast plants expressing KPHMT had elevated pantothenate levels in leaves, flowers siliques and seed in the range of 1.5-2.5 fold increase compared to the wild type plant. Seeds contained the highest vitamin content, indicating that they might be the ideal target for production purposes.

  1. Associations between perinatal factors and adiponectin and leptin in 9-year-old Mexican-American children

    PubMed Central

    Volberg, Vitaly; Harley, Kim G.; Aguilar, Raul S.; Rosas, Lisa G.; Huen, Karen; Yousefi, Paul; Davé, Veronica; Phan, Nguyet; Lustig, Robert H.; Eskenazi, Brenda; Holland, Nina

    2012-01-01

    Objectives To 1) determine whether perinatal factors (including maternal anthropometry and nutrition and early life growth measures) are associated with adiponectin and leptin levels in 9-year-old children, and 2) assess relationships between adiponectin, leptin and concurrent lipid profile in these children. Methods We measured plasma adiponectin and leptin for 146 mother - 9-year-old child pairs from the ongoing longitudinal birth cohort followed by the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS). Data on perinatal factors, including sociodemographics, maternal anthropometry and nutrition, and early life child growth were collected during pregnancy, birth and 6-month visits. Results Greater rate of weight and length gain during the first 6 months of life were associated with lower adiponectin in 9-year-olds (β=−2.0, P=0.04; β=−8.2, P=0.02, respectively) adjusting for child BMI. We found no associations between child adipokine levels and either maternal calorie, protein, total fat, saturated fat, fiber, sugar-sweetened beverage consumption during pregnancy or children’s concurrent sugar-sweetened beverage and fast food intake. Lipid profile in 9-year-old children closely reflected adiponectin but not leptin levels after adjustment for child BMI. Additionally, we report that child adipokine levels were closely related to their mothers’ levels at the 9-year-visit. Conclusion Overall, our results support the hypothesis that early life factors may contribute to altered adipokine levels in children. PMID:23325579

  2. Adiponectin gene ADIPOQ SNP associations with serum adiponectin in two female populations and effects of SNPs on promoter activity.

    PubMed

    Kyriakou, Theodosios; Collins, Laura J; Spencer-Jones, Nicola J; Malcolm, Claire; Wang, Xiaoling; Snieder, Harold; Swaminathan, Ramasamyiyer; Burling, Keith A; Hart, Deborah J; Spector, Tim D; O'Dell, Sandra D

    2008-01-01

    Adiponectin is an insulin sensitiser in muscle and liver, and low serum levels characterise obesity and insulin resistance. Eight tagging single nucleotide polymorphisms (tSNPs) in the ADIPOQ gene and promoter were selected, and association with serum adiponectin was tested, in two independent samples of Caucasian women: the Chingford Study (n = 808, mean age 62.8 +/- 5.9 years) and Twins UK (n = 2,718, mean age 47.4 +/- 12.6 years). In the Chingford cohort, -11391 G/A, -10066 G/A (rs182052), -7734 C/A (rs16861209), +276 G/T (rs1501299) and +3228 C/T (rs1063537) were significantly associated with fasting serum adiponectin (Ps = 1.00 x 10(-4) to 1.40 x 10(-2)). Associations with all except +3228 C/T were replicated in the Twins UK cohort (Ps = 3.19 x 10(-9) to 6.00 x 10(-3)). In Chingford subjects, the 12 most common 8-SNP haplotypes (frequency 1.90%) explained 2.85% (p = 5.00 x 10(-2)) and in Twins UK subjects, the four most common 5-SNP haplotypes (frequency > 5.00%) explained 1.66% of the variance (p = 5.83 x 10(-7)). To investigate effects of -11391 G/A (rs17300539) and -11377 C/G (rs266729) on promoter activity, 1.2 kb of the ADIPOQ promoter region was cloned in a luciferase reporter plasmid, and the four haplotypes were transfected in differentiated 3T3-L1 adipocytes. No significant allelic effects on promoter activity were found.

  3. Differential impact of changes in adiposity distribution on insulin resistance and adiponectin variations over 4 years in normal weight young adults.

    PubMed

    Lacerte, G; Langlois, M-F; Doyon, M; Brown, C; Carpentier, A C; Hivert, M-F

    2014-05-01

    The aim of the study was to evaluate the influence of weight gain and changes in adiposity distribution on insulin resistance and circulating adiponectin variations over 4 years in free-living normal weight young adults. In this prospective observational cohort (n=42 women, 18 men), anthropometric measurements and blood samples were collected in the fasting state at baseline and at 4 years. Insulin resistance was estimated using the homeostatic model assessment (HOMA-IR). Circulating adiponectin levels were determined by radioimmunoassay. To investigate increase in adiposity more specifically, subsidiary analyses were performed in a subgroup of individuals (n=31) who gained adiposity over the course of the 4-year follow-up (defined as gain >1% in percent body fat). Regression analyses were performed to adjust for sex, age, parental education, lifestyle, and fitness levels. At baseline, the participants were young adults (age=20.0 years old) in the normal weight range [body mass index (BMI)=22.7 kg/m2 (IQR=21.1-24.4)]. Median change in body fat percentage was +1.4% (IQR=-0.3-3.4; p=0.01) and in waist circumference was +1.2 cm (IQR=-2.6-5.3; p=0.05). In the subgroup of individuals who gained more than 1% body fat, increase in HOMA-IR was associated with an increase in BMI (r=0.44; p=0.01; p<0.01 in fully adjusted model), while decrease in adiponectin levels was associated with an increase in waist circumference (r=-0.38; p=0.03) but this was no longer significant after adjustment for sex and other potential confounders (p=0.14). In a population of young adults, small variations in adiposity within the normal weight range were associated with increase in insulin resistance.

  4. Chronic effects of centrally administered adiponectin on appetite, metabolism and blood pressure regulation in normotensive and hypertensive rats.

    PubMed

    Bassi, Mirian; do Carmo, Jussara M; Hall, John E; da Silva, Alexandre A

    2012-09-01

    Acute studies suggest that adiponectin may reduce sympathetic activity and blood pressure (BP) via actions on the central nervous system (CNS). However, the chronic effects of adiponectin on energy expenditure and cardiovascular function are still poorly understood. We tested if chronic intracerebroventricular (ICV) infusion of adiponectin (1 or 7μg/day) in Sprague-Dawley rats fed a high fat diet (HFD) for 8 weeks and at the high dose (7μg/day) in spontaneously hypertensive rats (SHRs), a hypertensive model associated with sympathetic overactivity, evoked chronic reductions in BP and heart rate (HR). We also determined if chronic ICV adiponectin infusion alters appetite, whole body oxygen consumption (VO(2)), and insulin and leptin levels. Neither dose of adiponectin infused for 7 days significantly altered BP or HR in the HFD group (115±2 to 112±2mmHg and 384±6 to 379±6bpm at 1μg/day; 109±3 to 111±3mmHg and 366±5 and 367±5bpm at 7μg/day). The higher dose slightly reduced food intake (14±1 to 11±1g/day), whereas VO(2), insulin and leptin levels were not affected by the treatment. In SHRs, ICV adiponectin infusion reduced appetite (22±2 to 12±2g/day) and insulin levels (∼55%), but did not alter BP (162±4 to 164±3mmHg) or HR (312±5 to 322±8bpm). These results suggest that adiponectin, acting via its direct actions on the CNS, has a small effect to reduce appetite and insulin levels, but it has no long-term action to reduce BP or HR, or to alter whole body metabolic rate.

  5. CHRONIC EFFECTS OF CENTRALLY ADMINISTERED ADIPONECTIN ON APPETITE, METABOLISM AND BLOOD PRESSURE REGULATION IN NORMOTENSIVE AND HYPERTENSIVE RATS

    PubMed Central

    Bassi, Mirian; do Carmo, Jussara M.; Hall, John E.; da Silva, Alexandre A.

    2012-01-01

    Acute studies suggest that adiponectin may reduce sympathetic activity and blood pressure (BP) via actions on the central nervous system (CNS). However, the chronic effects of adiponectin on energy expenditure and cardiovascular function are still poorly understood. We tested if chronic intracerebroventricular (ICV) infusion of adiponectin (1 or 7 µg/day) in Sprague-Dawley rats fed a high fat diet (HFD) for 8 weeks and at the high dose (7 µg/day) in spontaneously hypertensive rats (SHR), a hypertensive model associated with sympathetic overactivity, evoked chronic reductions in BP and heart rate (HR). We also determined if chronic ICV adiponectin infusion alters appetite, whole body oxygen consumption (VO2), and insulin and leptin levels. Neither dose of adiponectin infused for 7 days significantly altered BP or HR in the HFD group (115±2 to 112±2 mmHg and 384±6 to 379±6 bpm at 1 µg/day; 109±3 to 111±3 mmHg and 366±5 and 367±5 bpm at 7µg/day). The higher dose slightly reduced food intake (14±1 to 11±1 g/day), whereas VO2, insulin and leptin levels were not affected by the treatment. In SHRs, ICV adiponectin infusion reduced appetite (22±2 to 12±2 g/day) and insulin levels (~55%), but did not alter BP (162±4 to 164±3 mmHg) or HR (312±5 to 322±8 bpm). These results suggest that adiponectin, acting via its direct actions on the CNS, has a small effect to reduce appetite and insulin levels, but it has no long-term action to reduce BP or HR, or to alter whole body metabolic rate. PMID:22749987

  6. Effect of Increased Water Vapor Levels on TBC Lifetime

    SciTech Connect

    Pint, Bruce A; Garner, George Walter; Lowe, Tracie M; Haynes, James A; Zhang, Ying

    2011-01-01

    To investigate the effect of increased water vapor levels on thermal barrier coating (TBC) lifetime, furnace cycle tests were performed at 1150 C in air with 10 vol.% water vapor (similar to natural gas combustion) and 90 vol.%. Either Pt diffusion or Pt-modified aluminide bond coatings were applied to specimens from the same batch of a commercial second-generation single-crystal superalloy and commercial vapor-deposited yttria-stabilized zirconia (YSZ) top coats were applied. Three coatings of each type were furnace cycled to failure to compare the average lifetimes obtained in dry O{sub 2}, using the same superalloy batch and coating types. Average lifetimes with Pt diffusion coatings were unaffected by the addition of water vapor. In contrast, the average lifetime of Pt-modified aluminide coatings was reduced by more than 50% with 10% water vapor but only slightly reduced by 90% water vapor. Based on roughness measurements from similar specimens without a YSZ coating, the addition of 10% water vapor increased the rate of coating roughening more than 90% water vapor. Qualitatively, the amount of {beta}-phase depletion in the coatings exposed in 10% water vapor did not appear to be accelerated.

  7. The Role of Adiponectin in Breast Cancer: A Meta-Analysis

    PubMed Central

    Liu, Li-Yuan; Wang, Meng; Ma, Zhong-Bing; Yu, Li-Xiang; Zhang, Qiang; Gao, De-Zong; Wang, Fei; Yu, Zhi-Gang

    2013-01-01

    Published results suggests that high adiponectin level may decrease the risk of breast cancer. However, available evidence on breast cancer is conflicting. Therefore a meta-analysis was performed to assess the association between blood adiponectin and breast cancer risk. PubMed database, Web of Science, Elsevier Science, Springer Link and bibliographies of retrieved articles were searched for epidemiological studies published up to March 2013. Meta-analysis was performed on the combined effect values (OR) as well as standardized mean difference (SMD) including 17 studies. Fixed or random effect pooled measure was selected on the basis of homogeneity test among studies. The publication bias was assessed by the Egger’s regression asymmetry test and Begg’s rank correlation test with Begg’s funnel plot. Subgroup analyses and sensitivity analysis were also performed. A total of 13 studies involving 3578 breast cancer cases and 4363 controls contributed to the OR analysis. The high adiponectin level did not significantly affect breast cancer risk (OR=0.902, 95% CI=0.773–1.053). After excluding articles that were the key contributors to between-study heterogeneity, the OR of high adiponectin level was associated with decreased breast cancer risk (OR=0.838, 95% CI=0.744–0.943). There was a significantly association between high adiponectin level and postmenopausal breast cancer women (OR=0.752, 95%CI=0.604-0.936); and it was not associated with premenopausal breast cancer women (OR=0.895, 95%CI=0.638-1.256). The result of pooled measure on SMD was that the high adiponectin level was associated with decreased breast cancer risk (SMD= -0.348, 95% CI= -0.533--0.614) after excluding articles which were the key contributors to between-study heterogeneity. Our findings indicate that high adiponectin level might decrease the risk of postmenopausal breast cancer. More randomized clinical trials and observational studies are needed to confirm this association with

  8. Enforced physical inactivity increases endothelial microparticle levels in healthy volunteers.

    PubMed

    Navasiolava, Nastassia M; Dignat-George, Françoise; Sabatier, Florence; Larina, Irina M; Demiot, Claire; Fortrat, Jacques-Olivier; Gauquelin-Koch, Guillemette; Kozlovskaya, Inesa B; Custaud, Marc-Antoine

    2010-08-01

    A sedentary lifestyle has adverse effects on the cardiovascular system, including impaired endothelial functions. Subjecting healthy men to 7 days of dry immersion (DI) presented a unique opportunity to analyze the specific effects of enhanced inactivity on the endothelium. We investigated endothelial properties before, during, and after 7 days of DI involving eight subjects. Microcirculatory functions were assessed with laser Doppler in the skin of the calf. We studied basal blood flow and endothelium-dependent and -independent vasodilation. We also measured plasma levels of microparticles, a sign of cellular dysfunction, and soluble endothelial factors, reflecting the endothelial state. Basal flow and endothelium-dependent vasodilation were reduced by DI (22 + or - 4 vs. 15 + or - 2 arbitrary units and 29 + or - 6% vs. 12 + or - 6%, respectively, P < 0.05), and this was accompanied by an increase in circulating endothelial microparticles (EMPs), which was significant on day 3 (42 + or - 8 vs. 65 + or - 10 EMPs/microl, P < 0.05), whereas microparticles from other cell origins remained unchanged. Plasma soluble VEGF decreased significantly during DI, whereas VEGF receptor 1 and soluble CD62E were unchanged, indicating that the increase in EMPs was associated with a change in antiapoptotic tone rather than endothelial activation. Our study showed that extreme physical inactivity in humans induced by 7 days of DI causes microvascular impairment with a disturbance of endothelial functions, associated with a selective increase in EMPs. Microcirculatory endothelial dysfunction might contribute to cardiovascular deconditioning as well as to hypodynamia-associated pathologies. In conclusion, the endothelium should be the focus of special care in situations of acute limitation of physical activity.

  9. Cut-Off Value of Total Adiponectin for Managing Risk of Developing Metabolic Syndrome in Male Japanese Workers

    PubMed Central

    Hata, Akiko; Yonemoto, Koji; Shikama, Yosuke; Aki, Nanako; Kosugi, Chisato; Tamura, Ayako; Ichihara, Takako; Minagawa, Takako; Kuwamura, Yumi; Miyoshi, Masashi; Nakao, Takayuki; Funaki, Makoto

    2015-01-01

    Aim To determine the optimal cut-off value of serum total adiponectin for managing the risk of developing metabolic syndrome (MetS) in male Japanese workers. Methods A total of 365 subjects without MetS aged 20–60 years were followed up prospectively for a mean of 3.1 years. The accelerated failure-time model was used to estimate time ratio (TR) and cut-off value for developing MetS. Results During follow-up, 45 subjects developed MetS. Age-adjusted TR significantly declined with decreasing total adiponectin level (≤ 4.9, 5.0–6.6, 6.7–8.8 and ≥ 8.9 μg/ml, P for trend = 0.003). In multivariate analyses, TR of MetS was 0.12 (95% CI 0.02–0.78; P = 0.03) in subjects with total adiponectin level of 5.0–6.6 μg/ml, and 0.15 (95% CI 0.02–0.97; P = 0.047) in subjects with total adiponectin level ≤ 4.9 μg/ml compared with those with total adiponectin level ≥ 8.9 μg/ml. The accelerated failure-time model showed that the optimal cut-off value of total adiponectin for managing the risk of developing MetS was 6.2 μg/ml. In the multivariate-adjusted model, the mean time to the development of MetS was 78% shorter for total adiponectin level ≤ 6.2 μg/ml compared with > 6.2 μg/ml (TR 0.22, 95% CI: 0.08–0.64, P = 0.005). Conclusion Our findings suggest that the cut-off value for managing the risk of developing MetS is 6.2 μg/ml in male Japanese workers. Subjects with total adiponectin level ≤ 6.2 μg/ml developed MetS more rapidly than did those with total adiponectin level > 6.2 μg/ml. PMID:25705909

  10. Increase in voice level and speaker comfort in lecture rooms.

    PubMed

    Brunskog, Jonas; Gade, Anders Christian; Bellester, Gaspar Payá; Calbo, Lilian Reig

    2009-04-01

    Teachers often suffer from health problems related to their voice. These problems are related to their working environment, including the acoustics of the lecture rooms. However, there is a lack of studies linking the room acoustic parameters to the voice produced by the speaker. In this pilot study, the main goals are to investigate whether objectively measurable parameters of the rooms can be related to an increase in the voice sound power produced by speakers and to the speakers' subjective judgments about the rooms. In six different rooms with different sizes, reverberation times, and other physical attributes, the sound power level produced by six speakers was measured. Objective room acoustic parameters were measured in the same rooms, including reverberation time and room gain, and questionnaires were handed out to people who had experience talking in the rooms. It is found that in different rooms significant changes in the sound power produced by the speaker can be found. It is also found that these changes mainly have to do with the size of the room and to the gain produced by the room. To describe this quality, a new room acoustic quantity called "room gain" is proposed.

  11. Adiponectin Receptor Signaling on Dendritic Cells Blunts Antitumor Immunity

    PubMed Central

    Tan, Peng H.; Tyrrell, Helen E.J.; Gao, Liquan; Xu, Danmei; Quan, Jianchao; Gill, Dipender; Rai, Lena; Ding, Yunchuan; Plant, Gareth; Chen, Yuan; Xue, John Z.; Handa, Ashok I.; Greenall, Michael J.; Walsh, Kenneth; Xue, Shao-An

    2015-01-01

    Immune escape is a fundamental trait of cancer. Dendritic cells (DC) that interact with T cells represent a crucial site for the development of tolerance to tumor antigens, but there remains incomplete knowledge about how DC-tolerizing signals evolve during tumorigenesis. In this study, we show that DCs isolated from patients with metastatic or locally advanced breast cancer express high levels of the adiponectin receptors AdipoR1 and AdipoR2, which are sufficient to blunt antitumor immunity. Mechanistic investigations of ligand–receptor interactions on DCs revealed novel signaling pathways for each receptor. AdipoR1 stimulated IL10 production by activating the AMPK and MAPKp38 pathways, whereas AdipoR2 modified inflammatory processes by activating the COX-2 and PPARγ pathways. Stimulation of these pathways was sufficient to block activation of NF-κB in DC, thereby attenuating their ability to stimulate antigen-specific T-cell responses. Together, our findings reveal novel insights into how DC-tolerizing signals evolve in cancer to promote immune escape. Furthermore, by defining a critical role for adiponectin signaling in this process, our work suggests new and broadly applicable strategies for immunometabolic therapy in patients with cancer. PMID:25261236

  12. Serum adiponectin in HIV-1 and hepatitis C virus mono- and co-infected Kenyan injection drug users

    PubMed Central

    Ndombi, Eric M; Budambula, Valentine; Webale, Mark K; Musumba, Francis O; Wesongah, Jesca O; Mibei, Erick; Ahmed, Aabid A; Lihana, Raphael; Were, Tom

    2015-01-01

    Adiponectin is an important marker of anthropometric profiles of adipose tissue. However, association of adiponectin and adiposity in HIV mono- and co-infected and hepatitis (HCV) injection drug users (IDUs) has not been elucidated. Therefore, the relationship of total adiponectin levels with anthropometric indices of adiposity was examined in HIV mono-infected (anti-retroviral treatment, ART-naive, n=16 and -experienced, n=34); HCV mono-infected, n=36; HIV and HCV co-infected (ART-naive, n=5 and -experienced, n=13); uninfected, n=19 IDUs; and healthy controls, n=16 from coastal Kenya. Anthropometric indices of adiposity were recorded and total circulating adiponectin levels were measured in serum samples using enzyme-linked immunosorbent assay. Adiponectin levels differed significantly amongst the study groups (P<0.0001). Post-hoc analyses revealed decreased levels in HIV mono-infected ART-naive IDUs in comparison to uninfected IDUs (P<0.05) and healthy controls (P<0.05). However, adiponectin levels were elevated in HCV mono-infected IDUs relative to HIV mono-infected ART-naive (P<0.001) and -experienced (P<0.001) as well as HIV and HCV co-infected ART-naive (P<0.05) IDUs. Furthermore, adiponectin correlated with weight (ρ=0.687; P=0.003) and BMI (ρ=0.598; P=0.014) in HIV mono-infected ART-naive IDUs; waist circumference (ρ=−0.626; P<0.0001), hip (ρ=−0.561; P=0.001) circumference, and bust-to-waist ratio (ρ=0.561; P=0.001) in HIV mono-infected ART-experienced IDUs; waist girth (ρ=0.375; P=0.024) in HCV mono-infected IDUs; and waist-to-hip ratio (ρ=−0.872; P=0.048) in HIV and HCV co-infected ART-naive IDUs. Altogether, these results suggest suppression of adiponectin production in treatment-naive HIV mono-infected IDUs and that circulating adiponectin is a useful surrogate marker of altered adiposity in treatment-naive and -experienced HIV and HCV mono- and co-infected IDUs. PMID:26306727

  13. Cranberries (Oxycoccus quadripetalus) inhibit lipid metabolism and modulate leptin and adiponectin secretion in 3T3-L1 adipocytes.

    PubMed

    Kowalska, Katarzyna; Olejnik, Anna; Rychlik, Joanna; Grajek, Włodzimierz

    2015-10-15

    It has previously been shown that lyophilized cranberries (LCB) decreased lipid accumulation in 3T3-L1 cells and inhibited preadipocyte differentiation by down-regulation of the expression of key transcription factors (PPARγ, C/EBPα, SREBP1) of the adipogenesis pathway. To elucidate the molecular basis of anti-lipogenic activity of LCB, the expression of several genes involved in lipid metabolism, such as adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), hormone sensitive lipase (HSL) and perilipin 1 (PLIN1), was examined in the present study. Additionally, the effects of LCB on adiponectin and leptin expression and protein secretion were also investigated. LCB reduced lipid accumulation during preadipocyte differentiation by down-regulation of the mRNA level of aP2, FAS, LPL, HSL and PLIN1. Moreover, LCB decreased leptin gene expression and increased adiponectin gene expression and protein secretion in a dose-dependent manner. Therefore cranberries could be considered as bioactive factors, which are effective in the inhibition of adipose tissue mass production.

  14. Increased cerebrospinal fluid pyruvate levels in Alzheimer's disease.

    PubMed

    Parnetti, L; Gaiti, A; Polidori, M C; Brunetti, M; Palumbo, B; Chionne, F; Cadini, D; Cecchetti, R; Senin, U

    1995-10-27

    Impaired energy metabolism is an early, predominant feature in Alzheimer's disease. In order to find out simple, reliable 'in vivo' markers for the clinical-biological typization of the disorder, we measured cerebrospinal fluid (CSF) glucose, lactate and pyruvate levels in patients suffering from dementia of Alzheimer type (DAT) and in healthy elderly controls. DAT group showed remarkably higher levels of pyruvate (P = 0.01), with no overlap with the values obtained in controls. CSF pyruvate levels were also significantly associated with the severity of dementia. Therefore, CSF pyruvate levels neatly separate DAT patients from controls, having also pathogenetic value.

  15. Adiponectin inhibits Lrp6 phosphorylation and β-catenin signaling

    PubMed Central

    Reinke, Lauren; Lam, Anna P.; Flozak, Annette S.; Varga, John; Gottardi, Cara J.

    2016-01-01

    Adiponectin is a pleiotropic adipokine implicated in obesity, metabolic syndrome and cardiovascular disease. Recent studies have identified adiponectin as a negative regulator of tissue fibrosis. Wnt/β-catenin signaling has also been implicated in metabolic syndrome and can promote tissue fibrosis, but the extent to which adiponectin cross-regulates Wnt/β-catenin signaling is unknown. Using primary human dermal fibroblasts and recombinant purified proteins, we show that adiponectin can limit β-catenin accumulation and downstream gene activation by inhibiting Lrp6 phosphorylation, a key activation step in canonical Wnt signaling. Inhibition of Wnt3a-mediated Lrp6 phospho-activation is relatively rapid (e.g., by 30 minutes), and is not dependent on established adiponectin G-protein coupled receptors, AdipoR1 and R2, suggesting a more direct relationship to Lrp6 signaling. In contrast, the ability of adiponectin to limit Wnt-induced and baseline collagen production in fibroblasts requires AdipoR1/R2. These results suggest the possibility that the pleiotropic effects of adiponectin may be mediated through distinct cell surface receptor complexes. Accordingly, we propose that the anti-fibrotic activity of adiponectin may be mediated through AdipoR1/R2 receptors, while the ability of adiponectin to inhibit Lrp6 phospho-activation may be relevant to other recently established roles for Lrp6 signaling in glucose metabolism and metabolic syndrome. PMID:26797284

  16. Characterization of the weak calcium binding of trimeric globular adiponectin.

    PubMed

    Yu, Dongmei; Zhang, Chao; Wang, Han; Qin, Peiwu

    2013-06-01

    Adiponectin is secreted from adipose tissue and functions as a protein hormone in regulating glucose metabolism and fatty acid catabolism. Adiponectin plays an important role as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. Crystal structures of globular adiponectin have been resolved with three calcium-binding sites on the top of its central tunnel. However, the calcium-binding property of adiponectin remains elusive. Mouse globular adiponectin was cloned into pET11a and expressed in Escherichia coli. The folding of adiponectin was indicated by the spread of resonances in HSQC spectrum. Luminescence resonance energy transfer was used to obtain the binding constant (K(d)) of Tb(3+) and the inhibitor constant (K(i)) of Ca(2+) for globular adiponectin. The obtained calcium-binding affinity to adiponectin is relatively low (~2 mM), which indicates that the high concentration of adiponectin in circulating system may function as calcium storage bank and buffer the free calcium concentration.

  17. Lifestyle modification and behavior therapy effectively reduce body weight and increase serum level of brain-derived neurotrophic factor in obese non-diabetic patients with schizophrenia.

    PubMed

    Kuo, Feng-Chih; Lee, Chien-Hsing; Hsieh, Chang-Hsun; Kuo, Philip; Chen, Yi-Chyan; Hung, Yi-Jen

    2013-09-30

    The goal of the study was to elucidate the relationship between serum circulating brain-derived neurotrophic factor (BDNF) and body weight reduction via lifestyle modification and behavior therapy in obese non-diabetic patients with chronic schizophrenia. Thirty-three obese non-diabetic subjects with schizophrenia treated with stable antipsychotic medication in a day-care unit for at least 3 months were recruited. Thirty age-, body weight-matched subjects without psychiatric disorders were enrolled as controls. All participants underwent a 10-week weight reduction program, including lifestyle modification, psychosocial treatment, behavior therapy and exercise in the day-care unit. Blood biochemistry, serum BDNF, adipokine (adiponectin), inflammatory markers (C-reactive protein, tumor necrosis factor-alpha and interleukin-6) and oral glucose tolerance test were evaluated before and after the program. Serum BDNF concentrations were significantly lower among patients with schizophrenia compared to control subjects. Serum BDNF levels were significantly increased following the weight reduction program. Elevations in serum BDNF levels were positively correlated with body weight and body mass index reduction. Altogether, our results demonstrate that a non-pharmacological weight reduction program effectively reduces body weight with significant elevation of serum BDNF levels in obese non-diabetic patients with schizophrenia.

  18. Estuaries May Face Increased Parasitism as Sea Levels Rise

    NASA Astrophysics Data System (ADS)

    Wendel, JoAnna

    2014-12-01

    Invertebrates in estuaries could be at a greater risk of parasitism as climate change causes sea levels to rise. A new paper published 8 December in Proceedings of the National Academy of Sciences of the United States of America (doi:10.1073/pnas.1416747111) describes how rapid sea level rise in the Holocene affected the population of parasitic flatworms called trematodes.

  19. Adiponectin: a biomarker of obesity-induced insulin resistance in adipose tissue and beyond.

    PubMed

    Lu, Jin-Ying; Huang, Kuo-Chin; Chang, Lin-Chau; Huang, Ying-Shing; Chi, Yu-Chiao; Su, Ta-Chan; Chen, Chi-Ling; Yang, Wei-Shiung

    2008-09-01

    Adiponectin is one of the most thoroughly studied adipocytokines. Low plasma levels of adiponectin are found to associate with obesity, metabolic syndrome, diabetes and many other human diseases. From animal experiments and human studies, adiponectin has been shown to be a key regulator of insulin sensitivity. In this article, we review the evidence and propose that hypo-adiponectinemia is not a major cause of obesity. Instead, it is the result of obesity-induced insulin resistance in the adipose tissue. Hypo-adiponectinemia then mediates the metabolic effects of obesity on the other peripheral tissues, such as liver and skeletal muscle and may also exert some direct effects on end-organ damage. We propose that deciphering the molecular details governing the adiponectin gene expression and protein secretion will lead us to more comprehensive understanding of the mechanisms of insulin resistance in the adipose tissue and provide us new avenues for the therapeutic intervention of obesity and insulin resistance-related human disorders.

  20. FABP4 plasma levels are increased in familial combined hyperlipidemia

    PubMed Central

    Cabré, Anna; Lázaro, Iolanda; Cofán, Montserrat; Jarauta, Estibaliz; Plana, Núria; Garcia-Otín, Angel L.; Ascaso, Juan F.; Ferré, Raimón; Civeira, Fernando; Ros, Emilio; Masana, Lluís

    2010-01-01

    The lipid profile of familial combined hyperlipidemia (FCHL) shares some characteristics with atherogenic dyslipidemia seen in diabetes, metabolic syndrome, and obesity. Adipocyte fatty acid-binding protein 4 (FABP4) appears to be a determinant of atherogenic dyslipidemia. We examined relationships between FABP4 plasma concentrations, dyslipidemia, and metabolic variables in patients with FCHL. We studied 273 unrelated FCHL patients and 118 control subjects. FABP4 was higher in FCHL than controls, with mean levels of 21.8 (10.1) μg/l and 19.2 (9.2) μg/l, respectively (adjusted P= 0.012). In FCHL, FABP4 correlated to body mass index (BMI), waist circumference, insulin levels, and homeostasis model assessment (HOMA) index (all P< 0.05), but not to lipid levels, whereas in obese patients, FABP4 correlated to triglyceride levels (r = 0.303, P= 0.014) and very low density lipoprotein size (r = 0.502, P = 0.001), as determined by nuclear magnetic resonance. Associations of FABP4 with BMI and waist circumference, but not with insulin levels, persisted in this subgroup. Plasma FABP4 does not influence the lipid phenotype of FCHL. In a small subgroup of obese FCHL, FABP4 levels were associated with triglyceride-rich lipoproteins independent of insulin resistance. These results support a hyperlipidemic mechanism of FCHL different from similar metabolic conditions where fat mass is strongly related to FABP4 and hypertriglyceridemia. PMID:20388924

  1. Hip Osteonecrosis Is Associated with Increased Plasma IL-33 Level

    PubMed Central

    Ma, Jinhui; Guo, Wanshou; Li, Zirong; Li, Shirui; Wang, Peng

    2017-01-01

    The recently discovered IL-33 as an IL-1 cytokine family member has been proved to be specifically released from osteonecrotic bones. We aimed to investigate the potential role of IL-33 in the development of osteonecrosis of femoral head (ONFH). Forty patients diagnosed with ONFH and forty age-, sex-, and body mass index- (BMI-) matched healthy subjects were included in this prospective study between March 2016 and September 2016. A commercially available ELISA kit was used to test the level of plasma IL-33. The IL-33 levels were compared among different ARCO stages, CJFH types, and etiology groups. Plasma IL-33 levels were significantly higher in the ONFH patients than that in the control subjects. The levels of IL-33 did not differ significantly among the ONFH patients with different ARCO stages. The IL-33 levels of patients with CJFH type L3 were significantly higher than that of patients with types L1 and L2. No significant differences were observed in IL-33 levels between steroid-induced, alcohol-induced, and idiopathic patients. Our findings seem to indicate that IL-33 effects may be detrimental during ONFH, which appeared to be associated with the prognosis of ONFH. The IL-33 deserves particular attention in the pathogenesis of ONFH. PMID:28167850

  2. Leucine supplementation improves adiponectin and total cholesterol concentrations despite the lack of changes in adiposity or glucose homeostasis in rats previously exposed to a high-fat diet

    PubMed Central

    2011-01-01

    Background Studies suggest that leucine supplementation (LS) has a therapeutic potential to prevent obesity and to promote glucose homeostasis. Furthermore, regular physical exercise is a widely accepted strategy for body weight maintenance and also for the prevention of obesity. The aim of this study was to determine the effect of chronic LS alone or combined with endurance training (ET) as potential approaches for reversing the insulin resistance and obesity induced by a high-fat diet (HFD) in rats. Methods Forty-seven rats were randomly divided into two groups. Animals were fed a control diet-low fat (n = 10) or HFD (n = 37). After 15 weeks on HFD, all rats received the control diet-low fat and were randomly divided according to treatment: reference (REF), LS, ET, and LS+ET (n = 7-8 rats per group). After 6 weeks of treatment, the animals were sacrificed and body composition, fat cell volume, and serum concentrations of total cholesterol, HDL-cholesterol, triacylglycerol, glucose, adiponectin, leptin and tumor necrosis factor-alpha (TNF-α) were analyzed. Results At the end of the sixth week of treatment, there was no significant difference in body weight between the REF, LS, ET and LS+ET groups. However, ET increased lean body mass in rats (P = 0.019). In addition, ET was more effective than LS in reducing adiposity (P = 0.019), serum insulin (P = 0.022) and TNF-α (P = 0.044). Conversely, LS increased serum adiponectin (P = 0.021) levels and reduced serum total cholesterol concentration (P = 0.042). Conclusions The results showed that LS had no beneficial effects on insulin sensitivity or adiposity in previously obese rats. On the other hand, LS was effective in increasing adiponectin levels and in reducing total cholesterol concentration. PMID:21899736

  3. Ocean acidification increases fatty acids levels of larval fish.

    PubMed

    Díaz-Gil, Carlos; Catalán, Ignacio A; Palmer, Miquel; Faulk, Cynthia K; Fuiman, Lee A

    2015-07-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs.

  4. Ocean acidification increases fatty acids levels of larval fish

    PubMed Central

    Díaz-Gil, Carlos; Catalán, Ignacio A.; Palmer, Miquel; Faulk, Cynthia K.; Fuiman, Lee A.

    2015-01-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs. PMID:26179801

  5. Pyoderma gangrenosum with increased levels of serum cytokines.

    PubMed

    Kozono, Kana; Nakahara, Takeshi; Kikuchi, Satoko; Itoh, Eriko; Kido-Nakahara, Makiko; Furue, Masutaka

    2015-12-01

    A 66-year-old woman presented after an episode of accidental trauma with a painful ulcer on her scalp which rapidly enlarged in size, accompanied by central necrosis and undermining ulceration. The patient's past history was negative for underlying systemic disease, although she had had a similar post-traumatic intractable leg ulcer 3 years prior, which was unresponsive to surgical management but successfully treated with systemic steroids. A biopsied specimen from the scalp showed marked neutrophilic infiltrates in the dermis, compatible with a diagnosis of pyoderma gangrenosum (PG). The large ulcerative lesion responded very well to oral steroid therapy, showing rapid epithelialization. Serum levels of granulocyte colony-stimulating factor and interleukin-6 were significantly elevated prior to treatment, with decrease to normal levels after treatment. Serum tumor necrosis factor (TNF)-α and granulocyte macrophage colony-stimulating factor levels were within normal limits. The significance and pathogenic role of cytokine burst in PG is reviewed and discussed.

  6. Adiponectin is Protective against Oxidative Stress Induced Cytotoxicity in Amyloid-Beta Neurotoxicity

    PubMed Central

    Chan, Koon-Ho; Lam, Karen Siu-Ling; Cheng, On-Yin; Kwan, Jason Shing-Cheong; Ho, Philip Wing-Lok; Cheng, Kenneth King-Yip; Chung, Sookja Kim; Ho, Jessica Wing-Man; Guo, Vivian Yawei; Xu, Almin

    2012-01-01

    Beta-amyloid (Aβ ) neurotoxicity is important in Alzheimer’s disease (AD) pathogenesis. Aβ neurotoxicity causes oxidative stress, inflammation and mitochondrial damage resulting in neuronal degeneration and death. Oxidative stress, inflammation and mitochondrial failure are also pathophysiological mechanisms of type 2 diabetes (T2DM) which is characterized by insulin resistance. Interestingly, T2DM increases risk to develop AD which is associated with reduced neuronal insulin sensitivity (central insulin resistance). We studied the potential protective effect of adiponectin (an adipokine with insulin-sensitizing, anti-inflammatory and anti-oxidant properties) against Aβ neurotoxicity in human neuroblastoma cells (SH-SY5Y) transfected with the Swedish amyloid precursor protein (Sw-APP) mutant, which overproduced Aβ with abnormal intracellular Aβ accumulation. Cytotoxicity was measured by assay for lactate dehydrogenase (LDH) released upon cell death and lysis. Our results revealed that Sw-APP transfected SH-SY5Y cells expressed both adiponectin receptor 1 and 2, and had increased AMP-activated protein kinase (AMPK) activation and enhanced nuclear factor-kappa B (NF-κB) activation compared to control empty-vector transfected SH-SY5Y cells. Importantly, adiponectin at physiological concentration of 10 µg/ml protected Sw-APP transfected SH-SY5Y cells against cytotoxicity under oxidative stress induced by hydrogen peroxide. This neuroprotective action of adiponectin against Aβ neurotoxicity-induced cytotoxicity under oxidative stress involved 1) AMPK activation mediated via the endosomal adaptor protein APPL1 (adaptor protein with phosphotyrosine binding, pleckstrin homology domains and leucine zipper motif) and possibly 2) suppression of NF-κB activation. This raises the possibility of novel therapies for AD such as adiponectin receptor agonists. PMID:23300647

  7. Effects of radioiodine administration on serum concentrations of matrix metalloproteinases, adiponectin and thrombospondin-1

    PubMed Central

    2013-01-01

    Background In order to assess safety of radioactive iodine administration in the treatment of thyrotoxicosis, we measured concentrations of matrix metalloproteinase-2 (MMP-2), its main inhibitor – TIMP-2 (tissue inhibitor of MMP-2), matrix metalloproteinase-9 (MMP-9), its main inhibitor – TIMP-1, adiponectin, as well as pro-inflammatory and procancerogenic thrombospondin-1 (TSP-1). Design and patients The study involved 23 patients treated with radioiodine for thyrotoxicosis. Serum concentrations of TSH, free T4, free T3, MMP-2, MMP-9, TIMP-1, TIMP-2, total adiponectin and TSP-1 were measured by immunoassays just before radioiodine administration (visit 1), and subsequently, after 7 days (visit 2), 3 months (visit 3), 6 to 8 months (visit 4) and 15–18 months after radioiodine administration (visit 5). Results There were no acute changes in serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, adiponectin and TSP-1 (visit 1 vs. 2). Subsequently, there was an increase in MMP-2 (from 393±106 ng/ml to 774±424 ng/ml), TIMP-1 (from 177±76 ng/ml to 296±118 ng/ml), and adiponectin (from 16442±9490 ng/ml to 23518±9840 ng/ml), visit 1 to 5, respectively (p < 0.01). Further analysis revealed no significant change in MMP-2/TIMP-2 ratio, but there was a significant decrease in MMP-9/TIMP-1 ratio (p < 0.05), suggestive of possible decrease in free MMP-9 concentrations. Conclusions Our data reveal a significant and sustained increase in serum adiponectin, as well as possible decrease of free MMP-9 concentration after radioiodine administration. In contrast, there was no significant change of TSP-1. This might indicate overall safety of radioiodine treatment of thyrotoxicosis in terms of the risks of subsequent cardiovascular and neoplastic disease. PMID:23919647

  8. Regulation of lipin1 by nutritional status, adiponectin, sex and pituitary function in rat white adipose tissue.

    PubMed

    González, C Ruth; Novelle, Marta G; Caminos, Jorge E; Vázquez, María J; Luque, Raul M; López, Miguel; Nogueiras, Ruben; Diéguez, Carlos

    2012-02-01

    Lipin1 is a member of the lipin protein family that plays an important role in the regulation of lipid metabolism. The endogenous role of lipin1 was demonstrated by the fact that mutations in lipin1 caused lipodystrophy and metabolic disorders. The aim of this study was to assess the influence of nutritional status, pregnancy, insulin-sensitizers and pituitary hormones on lipin1 mRNA levels in adipose tissue of rats. Lipin1 gene expression was induced in conditions of hypoleptinemia (fasting) and leptin resistance (high fat diet), whereas it was decreased by high circulating leptin levels (leptin administration, pregnancy) and in leptin-deficient mice. Lipin1 mRNA levels were also decreased in adiponectin-deficient mice. Lipin1 mRNA levels are influenced by age in female rats, with peak expression at 25th day of life and decreasing thereafter. Consistently, ovariectomy increased lipin1 expression indicating that estrogens modulate lipin1. Finally, lipin1 was also regulated by pituitary hormones, since its expression was modified by thyroid status and growth hormone deficiency. Our observations indicate that: a) gWAT lipin1 mRNA levels are regulated by nutritional status, and leptin plays an important role in this regard, b) lipin1 is modulated by adiponectin, c) lipin1 is influenced by age and sex, and d) alterations in pituitary function modify lipin1 mRNA levels. To dissect the complicated interactions between key regulators of lipid metabolism like lipin1, may be important for the development of new therapies for the treatment and prevention of obesity and its associated disorders.

  9. Identification and characterization of CTRP9, a novel secreted glycoprotein, from adipose tissue that reduces serum glucose in mice and forms heterotrimers with adiponectin.

    PubMed

    Wong, G William; Krawczyk, Sarah A; Kitidis-Mitrokostas, Claire; Ge, Guangtao; Spooner, Eric; Hug, Christopher; Gimeno, Ruth; Lodish, Harvey F

    2009-01-01

    Adiponectin is a major insulin-sensitizing, multimeric hormone derived from adipose tissue that acts on muscle and liver to regulate whole-body glucose and lipid metabolism. Here, we describe a novel and highly conserved paralog of adiponectin designated as C1q/TNF-related protein (CTRP) 9. Of all the CTRP paralogs, CTRP9 shows the highest degree of amino acid identity to adiponectin in its globular C1q domain. CTRP9 is expressed predominantly in adipose tissue and females expresses higher levels of the transcript than males. Moreover, its expression levels in ob/ob mice changed in an age-dependent manner, with significant up-regulation in younger mice. CTRP9 is a secreted glycoprotein with multiple post-translational modifications in its collagen domain that include hydroxylated prolines and hydroxylated and glycosylated lysines. It is secreted as multimers (predominantly trimers) from transfected cells and circulates in the mouse serum with levels varying according to sex and metabolic state of mice. Furthermore, CTRP9 and adiponectin can be secreted as heterooligomers when cotransfected into mammalian cells, and in vivo, adiponectin/CTRP9 complexes can be reciprocally coimmunoprecipitated from the serum of adiponectin and CTRP9 transgenic mice. Biochemical analysis demonstrates that adiponectin and CTRP9 associate via their globular C1q domain, and this interaction does not require their conserved N-terminal cysteines or their collagen domains. Furthermore, we show that adiponectin and CTRP9 form heterotrimers. In cultured myotubes, CTRP9 specifically activates AMPK, Akt, and p44/42 MAPK signaling pathways. Adenovirus-mediated overexpression of CTRP9 in obese (ob/ob) mice significantly lowered serum glucose levels. Collectively, these results suggest that CTRP9 is a novel adipokine, and further study of CTRP9 will yield novel mechanistic insights into its physiological and metabolic function.

  10. Increased Cortisol and Cortisone Levels in Overweight Children

    PubMed Central

    Chu, Lanling; Sheng, Kangwei; Liu, Ping; Ye, Kan; Wang, Yu; Li, Chen; Kang, Xuejun; Song, Yuan

    2017-01-01

    Background It has been unclear whether relatively high cortisol and cortisone levels are related to overweight in childhood, parental body mass index (BMI), and family dietary habits. The aim of this study was to compare cortisol and cortisone levels in urine and saliva from overweight and normal children, as well as correlations between children’s BMI, parental BMI and family dietary behavior questionnaire score (QS). Material/Methods We analyzed the data from 52 overweight children and 53 age- and sex-matched normal-weight children aged 4–5 years. The concentrations of salivary cortisol (SF), salivary cortisone (SE), urinary cortisol (UF) and urinary cortisone (UE) were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The family dietary behavior QS was answered by the parent mainly responsible for the family diet. Results Average cortisol and cortisone levels were significantly higher in overweight children. There was no significant difference in the ratio of cortisol to cortisone (Rcc) and the marker of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activities. The results displayed correlations among cortisol, cortisone, and Rcc. Positive correlations were weak-to-moderate between BMI and SF, SE, UF, and UE. There were correlations between BMI and maternal BMI (mBMI), and BMI was significantly associated with QS. Conclusions Our results suggest that cortisol and cortisone levels are associated with overweight in children, but the 11β-HSD2 activities showed no significant differences. Unhealthy family diet was associated with higher BMI, UF, and UE, and families with maternal overweight or obesity had a higher prevalence of children’s overweight or obesity. PMID:28179618

  11. Adiposity Trajectory and Its associations with Plasma Adipokine Levels in Children and Adolescents – A Prospective Cohort Study

    PubMed Central

    Li, Shenghui; Liu, Rong; Arguelles, Lester; Wang, Guoying; Zhang, Jun; Shen, Xiaoming; Wang, Xiaobin

    2015-01-01

    Objective This study aimed to examine the associations of longitudinal adiposity measures with two adipokines, leptin and adiponectin, and their ratio in children and adolescents. Methods 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. Results After adjusting for possible confounders, our regression models revealed that BMI, %BF, and FMI, in both the baseline and follow-up survey, 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. Conclusions Our findings highlight the importance of adiposity surveillance and the utility of adipokines as biomarkers for adverse metabolic consequences of childhood adiposity. PMID:26704698

  12. 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.

  13. T-cadherin Is Essential for Adiponectin-mediated Revascularization*

    PubMed Central

    Parker-Duffen, Jennifer L.; Nakamura, Kazuto; Silver, Marcy; Kikuchi, Ryosuke; Tigges, Ulrich; Yoshida, Sumiko; Denzel, Martin S.; Ranscht, Barbara; Walsh, Kenneth

    2013-01-01

    Adipose tissue secretes protein factors that have systemic actions on cardiovascular tissues. Previous studies have shown that ablation of the adipocyte-secreted protein adiponectin leads to endothelial dysfunction, whereas its overexpression promotes wound healing. However, the receptor(s) mediating the protective effects of adiponectin on the vasculature is not known. Here we examined the role of membrane protein T-cadherin, which localizes adiponectin to the vascular endothelium, in the revascularization response to chronic ischemia. T-cadherin-deficient mice were analyzed in a model of hind limb ischemia where blood flow is surgically disrupted in one limb and recovery is monitored over 28 days by laser Doppler perfusion imaging. In this model, T-cadherin-deficient mice phenocopy adiponectin-deficient mice such that both strains display an impaired blood flow recovery compared with wild-type controls. Delivery of exogenous adiponectin rescued the impaired revascularization phenotype in adiponectin-deficient mice but not in T-cadherin-deficient mice. In cultured endothelial cells, T-cadherin deficiency by siRNA knockdown prevented the ability of adiponectin to promote cellular migration and proliferation. These data highlight a previously unrecognized role for T-cadherin in limb revascularization and show that it is essential for mediating the vascular actions of adiponectin. PMID:23824191

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

    PubMed

    Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana; Klegeris, Andis; Little, Jonathan P

    2014-03-28

    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 observed 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 (PI3K) 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.

  15. Plasma insulin, leptin, adiponectin, resistin, ghrelin, and melatonin in nonalcoholic steatohepatitis patients treated with melatonin.

    PubMed

    Gonciarz, Maciej; Bielański, Wladyslaw; Partyka, Robert; Brzozowski, Tomasz; Konturek, Piotr C; Eszyk, Jerzy; Celiński, Krzysztof; Reiter, Russel J; Konturek, Stanislaw J

    2013-03-01

    Insulin resistance, oxidative stress, and an abnormal production of adipokines and cytokines are implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH). Recently, we reported a significant improvement in plasma liver enzymes among patients with NASH treated with melatonin. In this study, we investigated the effect of melatonin, administered at a dose of 10 mg/day for 28 days to 16 patients with histologically proven NASH on insulin resistance (HOMA-IR), on the plasma levels of adiponectin, leptin, ghrelin, and resistin. Additionally, plasma levels of aminotransferases and gamma glutamyltranspeptidase as well as plasma concentrations of melatonin were evaluated. Median baseline values of HOMA-IR, leptin (ng/mL), and resistin (pg/mL) in patients with NASH were significantly higher in comparison with controls: 4.90 versus 1.60, 10.70 versus 4.30, and 152 versus 91, respectively. Median adiponectin level (μg/mL) was decreased in patients compared to controls: 6.40 versus 16.25; no significant difference in ghrelin levels between patients and controls was found. After melatonin treatment, the median value of HOMA-IR was significantly reduced by 60% as compared to baseline values, whereas adiponectin, leptin, and ghrelin plasma levels rose significantly by 119%, 33%, and 20%, respectively; the difference between pre-/posttreatment in plasma resistin levels was not significant. These findings make melatonin a suitable candidate for testing in patients with NASH in the large controlled clinical trials.

  16. White Adipocyte Adiponectin Exocytosis Is Stimulated via β3-Adrenergic Signaling and Activation of Epac1: Catecholamine Resistance in Obesity and Type 2 Diabetes.

    PubMed

    Komai, Ali M; Musovic, Saliha; Peris, Eduard; Alrifaiy, Ahmed; El Hachmane, Mickaël F; Johansson, Marcus; Wernstedt Asterholm, Ingrid; Olofsson, Charlotta S

    2016-11-01

    We investigated the physiological regulation of adiponectin exocytosis in health and metabolic disease by a combination of membrane capacitance patch-clamp recordings and biochemical measurements of short-term (30-min incubations) adiponectin secretion. Epinephrine or the β3-adrenergic receptor (AR) agonist CL 316,243 (CL) stimulated adiponectin exocytosis/secretion in cultured 3T3-L1 and in primary subcutaneous mouse adipocytes, and the stimulation was inhibited by the Epac (Exchange Protein directly Activated by cAMP) antagonist ESI-09. The β3AR was highly expressed in cultured and primary adipocytes, whereas other ARs were detected at lower levels. 3T3-L1 and primary adipocytes expressed Epac1, whereas Epac2 was undetectable. Adiponectin secretion could not be stimulated by epinephrine or CL in adipocytes isolated from obese/type 2 diabetic mice, whereas the basal (unstimulated) adiponectin release level was elevated twofold. Gene expression of β3AR and Epac1 was reduced in adipocytes from obese animals, and corresponded to a respective ∼35% and ∼30% reduction at the protein level. Small interfering RNA-mediated knockdown of β3AR (∼60%) and Epac1 (∼50%) was associated with abrogated catecholamine-stimulated adiponectin secretion. We propose that adiponectin exocytosis is stimulated via adrenergic signaling pathways mainly involving β3ARs. We further suggest that adrenergically stimulated adiponectin secretion is disturbed in obesity/type 2 diabetes as a result of the reduced expression of β3ARs and Epac1 in a state we define as "catecholamine resistance."

  17. Adiponectin Regulates the Polarization and Function of Microglia via PPAR-γ Signaling Under Amyloid β Toxicity

    PubMed Central

    Song, Juhyun; Choi, Seong-Min; Kim, Byeong C.

    2017-01-01

    Alzheimer’s disease (AD), characterized by the abnormal accumulation of amyloid beta (Aβ), is gradually increasing globally. Given that AD is considered a neuroinflammatory disease, recent studies have focused on the cellular mechanisms in brain inflammatory conditions that underlie AD neuropathology. Microglia are macrophage cells in the central nervous system (CNS) that are activated in response to Aβ condition. The function of microglia contributes to the neuroinflammation in AD brain, suggesting that microglia regulate the production of inflammatory mediators and contribute to the regeneration of damaged tissues. Adiponectin, an adipokine derived from adipose tissue, has been known to regulate inflammation and control macrophages during oxidative stress conditions. In present study, we investigated whether adiponectin influences the polarization and function of microglia under Aβ toxicity by examining alterations of BV2 microglia function and polarization by Acrp30 (a globular form of adiponectin) treatment using reverse transcription PCR, western blotting and immunofluorescence staining. Acrp30 promoted the induction of the M2 phenotype, and regulated the inflammatory responses through peroxisome proliferator-activated receptor (PPAR)-γ signaling under Aβ toxicity. In addition, Acrp30 boosted the capacity of Aβ scavenging in microglia. Taken together, we suggest that adiponectin may control the function of microglia by promoting anti-inflammatory responses through PPAR- γ signaling. Hence, we conclude that adiponectin may act as a critical controller of microglia function in the AD brain. PMID:28326017

  18. Adiponectin inhibits neutrophil apoptosis via activation of AMP kinase, PKB and ERK 1/2 MAP kinase.

    PubMed

    Rossi, Alessandra; Lord, Janet M

    2013-12-01

    Neutrophils are abundant, short-lived leukocytes that play a key role in the immune defense against microbial infections. These cells die by apoptosis following activation and uptake of microbes and will also enter apoptosis spontaneously at the end of their lifespan if they do not encounter a pathogen. Adiponectin exerts anti-inflammatory effects on neutrophil antimicrobial functions, but whether this abundant adipokine influences neutrophil apoptosis is unknown. Here we report that adiponectin in the physiological range (1-10 μg/ml) reduced apoptosis in resting neutrophils, decreasing caspase-3 cleavage and maintaining Mcl-1 expression by stabilizing this anti-apoptotic protein. We show that adiponectin induced phosphorylation of AMP-activated kinase (AMPK), protein kinase B (PKB), extracellular signal-regulated kinase (ERK 1/2) and p38 mitogen activated protein kinase (MAPK). Pharmacological inhibition of AMPK, PKB and ERK 1/2 ablated the pro-survival effects of adiponectin and treatment of neutrophils with an AMPK specific activator (AICAR) and AMPK inhibitor (compound C) respectively decreased and increased apoptosis. Finally, activation of AMPK by AICAR or adiponectin also decreased ceramide accumulation in the neutrophil cell membrane, a process involved in the early stages of spontaneous apoptosis, giving another possible mechanism downstream of AMPK activation for the inhibition of neutrophil apoptosis.

  19. Increase of inherent protection level in spent nuclear fuel

    SciTech Connect

    Krasnobaev, A.; Kryuchkov, E.; Glebov, V.

    2006-07-01

    The paper is devoted to upgrading inherent proliferation protection of fissionable nuclear materials (FNM). Some possibilities were investigated to form high radiation barrier inside spent fuel assemblies (SFA) discharged from power reactors of VVER-1000 type and research reactors of IRT type. The radiation barrier is estimated in the terms of rate of equivalent dose (RED) at 30-cm distance from SFA. The values of RED were calculated with application of the computer code package SCALE 4.3. The paper considers the criteria adopted for estimation of FNM proliferation resistance. The paper presents numerical results on a component-wise analysis of the radiation barrier in SFA from reactors of VVER-1000 and IRT type and on capability of various radionuclides to prolong action of the radiation barrier. Isotopic admixtures were selected and amounts of these admixtures were evaluated for significant prolongation of the radiation barrier action at the levels of the radiation standards used for estimation of FNM proliferation resistance. The paper considers vulnerability of the radiation barriers in respect to thermal processing of spent fuel. (authors)

  20. Increased carbon tetrachloride hepatotoxicity after low-level ethanol consumption.

    PubMed

    Strubelt, O; Obermeier, F; Siegers, C P; Vöpel, M

    1978-07-01

    Male rats provided with a 5 or 15% (v/v) ethanol solution as the sole source of fluid consumed ethanol at a rate of 11.4 or 24.9% of total calories (4.2 or 8.3 g/kg daily). After ethanol consumption lasting 1, 2 and 3 weeks the hepatotoxicity of CCl4 (0.1 ml/kg i.p.) was elevated by determination of serum activities of glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase ( GPT), sorbitol dehydrogenase (SDH) and histological investigations. Carbon tetrachloride (CCl4)-induced liver damage was significantly greater in rats provided with ethanol than in the tap-water consuming controls. This potentiation of CCl4 hepatotoxicicty was fully developed already after a 1-week exposition to ethanol and was greater in the 15% than in the 5% ethanol group. Ethanol alone did not influence serum enzyme activities but increased microsomal aniline hydroxylation. There was, however, no clear-cut parallelism between potentiation of CCl4 hepatotoxicity and activation of aniline hydroxylation.

  1. Adiponectin Inhibits LPS-Induced HMGB1 Release through an AMP Kinase and Heme Oxygenase-1-Dependent Pathway in RAW 264 Macrophage Cells

    PubMed Central

    Kaede, Ryuji; Okamatsu-Ogura, Yuko

    2016-01-01

    High mobility group protein B1 (HMGB1) is a late inflammatory mediator that exaggerates septic symptoms. Adiponectin, an adipokine, has potent anti-inflammatory properties. However, possible effects of adiponectin on lipopolysaccharide- (LPS-) induced HMGB1 release are unknown. The aim of this study was to investigate effects of full length adiponectin on HMGB1 release in LPS-stimulated RAW 264 macrophage cells. Treatment of the cells with LPS alone significantly induced HMGB1 release associated with HMGB1 translocation from the nucleus to the cytosol. However, prior treatment with adiponectin suppressed LPS-induced HMGB1 release and translocation. The anti-inflammatory cytokine interleukin- (IL-) 10 similarly suppressed LPS-induced HMGB1 release. Adiponectin treatment decreased toll-like receptor 4 (TLR4) mRNA expression and increased heme oxygenase- (HO-) 1 mRNA expression without inducing IL-10 mRNA, while IL-10 treatment decreased TLR2 and HMGB1 mRNA expression and increased the expression of IL-10 and HO-1 mRNA. Treatment with the HO-1 inhibitor ZnPP completely prevented the suppression of HMGB1 release by adiponectin but only partially inhibited that induced by IL-10. Treatment with compound C, an AMP kinase (AMPK) inhibitor, abolished the increase in HO-1 expression and the suppression of HMGB1 release mediated by adiponectin. In conclusion, our results indicate that adiponectin suppresses HMGB1 release by LPS through an AMPK-mediated and HO-1-dependent IL-10-independent pathway. PMID:27313399

  2. Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

    SciTech Connect

    Liu, Yansong; Xu, Dan; Feng, Jianghua; Kou, Hao; Liang, Gai; Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin; Magdalou, Jacques; Wang, Hui

    2012-07-15

    The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by {sup 1}H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine

  3. Differential effects of olanzapine and clozapine on plasma levels of adipocytokines and total ghrelin.

    PubMed

    Lu, Mong-Liang; Wang, Tsu-Nai; Lin, Tsang-Yaw; Shao, Wen-Chuan; Chang, Sheng-Huang; Chou, Jen-Yu; Ho, Yi-Feng; Liao, Yin-To; Chen, Vincent Chin-Hung

    2015-04-03

    Second-generation antipsychotics (SGAs) have been associated with an increased liability for weight gain and metabolic side effects. Among SGAs, clozapine and olanzapine had great liability to induce weight gain and metabolic adverse reactions. Leptin, adiponectin, and total ghrelin play important roles in energy homeostasis and are suggested to be biomarkers of metabolic disturbances. The purpose of the present study was to investigate the differential effects of antipsychotics (olanzapine and clozapine) on the levels of adipocytokines (leptin and adiponectin) and total ghrelin. Three hundred and thirty-three patients with schizophrenia under clozapine or olanzapine monotherapy were recruited. Control participants were recruited from a healthy community population based on a health investigation (N=119). Fasting blood samples for glucose, cholesterol, triglycerides, leptin, adiponectin, and total ghrelin were analyzed. There were significant differences in the levels of cholesterol, triglycerides, and glucose between these three groups. Post hoc comparisons showed that the olanzapine group had the highest levels of cholesterol and triglycerides. The levels of leptin, adiponectin, and total ghrelin were also significantly different between the three groups after controlling age and body mass index (BMI). Post hoc comparisons showed that the olanzapine group had the lowest levels of adiponectin and total ghrelin. The present study found that the uses of olanzapine and clozapine were associated with changes in adipocytokines and total ghrelin, even after adjusting potential confounding factors. Olanzapine had greater influences on adiponectin and total ghrelin than clozapine. The changes in adipocytokines and total ghrelin were a direct effect of antipsychotics on hormonal pathways of energy homeostasis, rather than the result of weight gain.

  4. Peroxisome Proliferator-Activated Receptor α Reduces Endothelin-1-Caused Cardiomyocyte Hypertrophy by Inhibiting Nuclear Factor-κB and Adiponectin

    PubMed Central

    Jen, Hsu-Lung; Liu, Po-Len; Chen, Jaw-Wen; Lin, Shing-Jong

    2016-01-01

    Peroxisome proliferator-activated receptor α (PPARα) plays a role in the pathogenesis of cardiac hypertrophy, although its underlying mechanism remains unclear. The purpose of this study was to evaluate the effect of PPARα activation on endothelin-1- (ET-1-) caused cardiomyocyte hypertrophy and explore its underlying mechanisms. Human cardiomyocytes (HCMs) were cultured with or without ET-1, whereafter the inhibitory effects of fenofibrate, a PPARα activator, on cell size and adiponectin protein were tested. We examined the activation of extracellular signal-regulated kinase (ERK) and p38 proteins caused by ET-1 and the inhibition of the ERK and p38 pathways on ET-1-induced cell size and adiponectin expression. Moreover, we investigated the interaction of PPARα with adiponectin and nuclear factor-κB (NF-κB) by electrophoretic mobility shift assays and coimmunoprecipitation. ET-1 treatment significantly increased cell size, suppressed PPARα expression, and enhanced the expression of adiponectin. Pretreatment with fenofibrate inhibited the increase in cell size and enhancement of adiponectin expression. ET-1 significantly activated the ERK and p38 pathways, whereas PD98059 and SB205380, respectively, inhibited them. Our results suggest that activated PPARα can decrease activation of adiponectin and NF-κB and inhibit ET-1-induced cardiomyocyte hypertrophy. PMID:27807394

  5. Adiponectin signaling and function in insulin target tissues

    PubMed Central

    Ruan, Hong; Dong, Lily Q.

    2016-01-01

    Obesity-linked type 2 diabetes is one of the paramount causes of morbidity and mortality worldwide, posing a major threat on human health, productivity, and quality of life. Despite great progress made towards a better understanding of the molecular basis of diabetes, the available clinical counter-measures against insulin resistance, a defect that is central to obesity-linked type 2 diabetes, remain inadequate. Adiponectin, an abundant adipocyte-secreted factor with a wide-range of biological activities, improves insulin sensitivity in major insulin target tissues, modulates inflammatory responses, and plays a crucial role in the regulation of energy metabolism. However, adiponectin as a promising therapeutic approach has not been thoroughly explored in the context of pharmacological intervention, and extensive efforts are being devoted to gain mechanistic understanding of adiponectin signaling and its regulation, and reveal therapeutic targets. Here, we discuss tissue- and cell-specific functions of adiponectin, with an emphasis on the regulation of adiponectin signaling pathways, and the potential crosstalk between the adiponectin and other signaling pathways involved in metabolic regulation. Understanding better just why and how adiponectin and its downstream effector molecules work will be essential, together with empirical trials, to guide us to therapies that target the root cause(s) of type 2 diabetes and insulin resistance. PMID:26993044

  6. Porcine adiponectin receptor 1 transgene resists high-fat/sucrose diet-induced weight gain, hepatosteatosis and insulin resistance in mice.

    PubMed

    Liu, Bing-Hsien; Lin, Yuan-Yu; Wang, Ya-Chin; Huang, Chao-Wei; Chen, Chih-Chien; Wu, Shinn-Chih; Mersmann, Harry J; Cheng, Winston T K; Ding, Shih-Torng

    2013-01-01

    Adiponectin and its receptors have been demonstrated to play important roles in regulating glucose and lipid metabolism in mice. Obesity, type II diabetes and cardiovascular disease are highly correlated with down-regulated adiponectin signaling. In this study, we generated mice overexpressing the porcine Adipor1 transgene (pAdipor1) to study its beneficial effects in metabolic syndromes as expressed in diet-induced obesity, hepatosteatosis and insulin resistance. Wild-type (WT) and pAdipor1 transgenic mice were fed ad libitum with a standard chow diet (Chow) or a high-fat/sucrose diet (HFSD) for 24 weeks, beginning at 6 to 7 weeks of age. There were 12 mice per genetic/diet/sex group. When challenged with HFSD to induce obesity, the pAdipor1 transgenic mice resisted development of weight gain, hepatosteatosis and insulin resistance. These mice had lowered plasma adiponectin, triglyceride and glycerol concentrations compared to WT mice. Moreover, we found that (indicated by mRNA levels) fatty acid oxidation was enhanced in skeletal muscle and adipose tissue, and liver lipogenesis was inhibited. The pAdipor1 transgene also restored HFSD-reduced phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose transporter 4 mRNA in the adipose tissues, implying that the increased Pck1 may promote glyceroneogenesis to reduce glucose intolerance and thus activate the flux of glyceride-glycerol to resist diet-induced weight gain in the adipose tissues. Taken together, we demonstrated that pAdipor1 can prevent diet-induced weight gain and insulin resistance. Our findings may provide potential therapeutic strategies for treating metabolic syndromes and obesity, such as treatment with an ADIPOR1 agonist or activation of Adipor1 downstream targets.

  7. Adiponectin enhances osteogenic differentiation in human adipose-derived stem cells by activating the APPL1-AMPK signaling pathway

    SciTech Connect

    Chen, Tong; Wu, Yu-wei; Lu, Hui; Guo, Yuan; Tang, Zhi-hui

    2015-05-29

    Human adipose-derived stem cells (hASCs) are multipotent progenitor cells with multi-lineage differentiation potential including osteogenesis and adipogenesis. While significant progress has been made in understanding the transcriptional control of hASC fate, little is known about how hASC differentiation is regulated by the autocrine loop. The most abundant adipocytokine secreted by adipocytes, adiponectin (APN) plays a pivotal role in glucose metabolism and energy homeostasis. Growing evidence suggests a positive association between APN and bone formation yet little is known regarding the direct effects of APN on hASC osteogenesis. Therefore, this study was designed to investigate the varied osteogenic effects and regulatory mechanisms of APN in the osteogenic commitment of hASCs. We found that APN enhanced the expression of osteoblast-related genes in hASCs, such as osteocalcin, alkaline phosphatase, and runt-related transcription factor-2 (Runx2, also known as CBFa1), in a dose- and time-dependent manner. This was further confirmed by the higher expression levels of alkaline phosphatase and increased formation of mineralization nodules, along with the absence of inhibition of cell proliferation. Importantly, APN at 1 μg/ml was the optimal concentration, resulting in maximum deposition of calcium nodules, and was significant superior to bone morphogenetic protein 2. Mechanistically, we found for the first time that APN increased nuclear translocation of the leucine zipper motif (APPL)-1 as well as AMP-activated protein kinase (AMPK) phosphorylation, which were reversed by pretreatment with APPL1 siRNA. Our results indicate that APN promotes the osteogenic differentiation of hASCs by activating APPL1-AMPK signaling, suggesting that manipulation of APN is a novel therapeutic target for controlling hASC fate. - Highlights: • Adiponectin enhances osteogenic differentiation in human adipose-derived stem cells. • The knock-down of APPL1 block the enhancement of

  8. Chromium dinicocysteinate supplementation can lower blood glucose, CRP, MCP-1, ICAM-1, creatinine, apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkB, Akt, and Glut-2 in livers of Zucker diabetic fatty rats

    PubMed Central

    Jain, Sushil K.; Croad, Jennifer L.; Velusamy, Thirunavukkarasu; Rains, Justin L.; Bull, Rebeca

    2011-01-01

    Aim Chromium and cysteine supplementation can improve glucose metabolism in animal studies. This study examined the hypothesis that a cysteinate complex of chromium is significantly beneficial than either of them in lowering blood glucose and vascular inflammation markers in ZDF rats. Methods Starting at the age of 6 wks, ZDF rats were supplemented orally (daily gavages for 8 more wks) with saline-placebo (D) or chromium (400µg Cr/KgBW) as chromium-dinicocysteinate (CDNC), chromium-dinicotinate (CDN), or chromium-picolinate (CP) or equimolar L-cysteine (LC, img/Kg BW), and fed Purina 5008 diet for 8 wks. ZDF rats of 6 wks age before any supplementations and onset of diabetes were considered as baseline (BL). Results D rats showed elevated levels of fasting blood glucose, HbA1, CRP, MCP-1, ICAM-1 and oxidative stress (LP) and lower adiponectin and vitamin C, when compared to BL rats. In comparison to D group, CDNC group had significantly lower blood glucose, HbA1, CRP, MCP-1, ICAM-1 and LP and increased vitamin C and adiponectin levels. CDN, CP or LC showed significantly less or no effect on these biomarkers. Only CDNC lowered blood creatinine levels in comparison to D. While CDN and CP had no effect, activation of NFkB, Akt and GLUT-2 levels were decreased, IRS-1 activation increased in livers of CDNC-rats. CDNC effect on glycemia, NFkB, Akt and IRS-1 in liver was significantly greater compared with LC. Blood chromium levels did not differ between Cr-groups. Exogenous vitamin C supplementation significantly inhibited MCP-1 secretion in U937 monocytes cultured in high-glucose-medium. Conclusions CDNC is a potent hypoglycemic compound with anti-inflammatory activity apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkB, Akt, and Glut-2 and increased IRS-1 activation in livers of type 2 diabetic rats. PMID:20306473

  9. Chromium dinicocysteinate supplementation can lower blood glucose, CRP, MCP-1, ICAM-1, creatinine, apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkappaB, Akt, and Glut-2 in livers of zucker diabetic fatty rats.

    PubMed

    Jain, Sushil K; Croad, Jennifer L; Velusamy, Thirunavukkarasu; Rains, Justin L; Bull, Rebeca

    2010-09-01

    Chromium and cysteine supplementation can improve glucose metabolism in animal studies. This study examined the hypothesis that a cysteinate complex of chromium is significantly beneficial than either of them in lowering blood glucose and vascular inflammation markers in Zucker diabetic fatty (ZDF) rats. Starting at the age of 6 wk, ZDF rats were supplemented orally (daily gavages for 8 more weeks) with saline-placebo (D) or chromium (400 microg Cr/Kg body weight) as chromium dinicocysteinate (CDNC), chromium dinicotinate (CDN) or chromium picolinate (CP) or equimolar L-cysteine (LC, img/Kg body weight), and fed Purina 5008 diet for 8 wk. ZDF rats of 6 wk age before any supplementations and onset of diabetes were considered as baseline. D rats showed elevated levels of fasting blood glucose, HbA(1), CRP, MCP-1, ICAM-1 and oxidative stress (lipid peroxidation) and lower adiponectin and vitamin C, when compared with baseline rats. In comparison to D group, CDNC group had significantly lower blood glucose, HbA(1), CRP, MCP-1, ICAM-1 and lipid peroxidation and increased vitamin C and adiponectin levels. CDN, CP or LC showed significantly less or no effect on these biomarkers. Only CDNC lowered blood creatinine levels in comparison to D. While CDN and CP had no effect, activation of NFkappaB, Akt and glucose transporter-2 levels were decreased, insulin receptor substrate 1 (IRS-1) activation increased in livers of CDNC-rats. CDNC effect on glycemia, NFkappaB, Akt and IRS-1 in liver was significantly greater compared with LC. Blood chromium levels did not differ between Cr-groups. Exogenous vitamin C supplementation significantly inhibited MCP-1 secretion in U937 monocytes cultured in high-glucose-medium. CDNC is a potent hypoglycemic compound with anti-inflammatory activity apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkappaB, Akt, and Glut-2 and increased IRS-1 activation in livers of type 2 diabetic rats.