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Sample records for adiponectin leptin resistin

  1. [Adipokines: adiponectin, leptin, resistin and coronary heart disease risk].

    PubMed

    Kopff, Barbara; Jegier, Anna

    2005-01-01

    Visceral obesity is among the known risk factors of atherosclerotic cardiovascular diseases. As long as adipose tissue was considered only an inert store of excess energy, accumulated in triglycerides, explanation of the mechanisms causing increased cardiovascular risk in obesity was difficult. Finding that the adipose tissue is an active endocrine organ and that the adipokines secreted in it influence several metabolic processes, allowed better understanding of this correlation. Several disturbances in secretion, function and balance of adipokines occur in the course of obesity. Changes of adiponectin, leptin and resistin concentrations are among the reasons of accelerated atherosclerosis occurring in the visceral adiposity. Adiponectin concentrations are decreased in visceral adiposity. Adiponectin is adipokine possessing antiatherogenic properties. It's effects exerted though the specific receptors in skeletal muscles and liver include decreased insulin resistance and improved plasma lipid profile. Acting directly in the vessel wall adiponectin prevents development of atheromatic lesions by inhibiting production of adhesive molecules and formation of foam cells. It has been found that decreased adiponectin concentrations are connected not only with increased coronary risk but also with progression of atherosclerosis in coronary vessels. Moreover it was found that adiponectin plasma concentration is significantly decreased in acute coronary incidences. Leptin regulates energy metabolism and balance. The concentrations of this adipokine are increased in obesity and correlate with insulin resistance. Hiperleptinemia has been also recognized as cardiovascular diseases risk factor. Resistin is considered to be a substance increasing insulin resistance, however the exact mechanisms are not known. Resistin plasma concentrations are increased in obese subjects and correlate with the inflammatory state that underlies the initiation and progression of atherosclerotic

  2. Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans.

    PubMed

    Yannakoulia, Mary; Yiannakouris, Nikos; Blüher, Susann; Matalas, Antonia-Leda; Klimis-Zacas, Dorothy; Mantzoros, Christos S

    2003-04-01

    The adipocyte-derived hormones leptin [which circulates in a free form and bound to a soluble leptin receptor (sOB-R)], adiponectin, and resistin play a key role in regulating energy homeostasis and metabolism. We assessed the association between body composition, total energy, and macronutrient intake and serum leptin, sOB-R, free leptin index, adiponectin, and resistin concentrations in 61 female and 53 male consecutively enrolled healthy Greek students. In this cross-sectional study, total energy and macronutrient intake were determined using 3-d food records. Body composition was assessed by bioelectrical impedance analysis; fasting blood samples were taken for the measurement of total leptin, sOB-R, adiponectin, and resistin; and the ratio leptin/sOB-R was used as an index of free leptin. Serum sOB-R concentrations were lower in the female subjects compared with the males (27.24 +/- 29.06 vs. 50.14 +/- 39.74 ng/ml, P < 0.001), whereas leptin, adiponectin, and resistin concentrations were significantly higher in females (leptin: 9.93 +/- 6.01 vs. 3.27 +/- 2.54 ng/ml, P < 0.001; adiponectin: 11.40 +/- 6.73 micro g/ml vs. 4.90 +/- 2.79 micro g/ml; P < 0.001; resistin: 16.86 +/- 5.39 ng/ml in females vs. 14.00 +/- 7.16 ng/ml in males, P < 0.02). Simple regression analysis showed that, in both genders, leptin, free leptin index, adiponectin, and resistin correlated positively with body fat mass and negatively with waist to hip ratio. sOB-R correlated negatively with body fat mass and positively with waist to hip ratio. Multiple regression analysis models controlling for gender, body fat, and total energy intake demonstrated that sOB-R is positively associated with energy intake from carbohydrates and negatively with energy intake from dietary fat, whereas free leptin index is negatively associated with energy intake from carbohydrates and positively with energy intake from dietary fat. No statistically significant correlations were observed between serum

  3. Resistin, Visfatin, Adiponectin, and Leptin: Risk of Breast Cancer in Pre- and Postmenopausal Saudi Females and Their Possible Diagnostic and Predictive Implications as Novel Biomarkers

    PubMed Central

    Assiri, Adel M. A.; Kamel, Hala F. M.; Hassanien, Mohamed F. R.

    2015-01-01

    The mechanisms of obesity-induced breast carcinogenesis are not clear. One hypothesis is that high levels of adipokines could promote breast cancer (BC) development. The aim of this study was to investigate the correlation of resistin, visfatin, adiponectin, and leptin with BC risk in pre- and postmenopausal females. A total of 82 BC newly diagnosed and histologically confirmed patients and 68 age and BMI matched healthy controls were enrolled. Both groups were subdivided into post- and premenopausal subgroups. Resistin, visfatin, adiponectin, and leptin were measured by ELISA. There were significantly higher levels of leptin, resistin, and visfatin in postmenopausal BC patients than their respective controls. Only in postmenopausal subgroups, leptin, resistin, and visfatin levels were positively correlated with TNM staging, tumor size, lymph node (LN) metastasis, and histological grading. In postmenopausal females, multivariate logistic regression analysis revealed that adiponectin, leptin, visfatin, and resistin were risk factors for BC. Our results suggested that serum resistin, leptin, adiponectin, and visfatin levels as risk factors for postmenopausal BC may provide a potential link with clinicopathological features and are promising to be novel biomarkers for postmenopausal BC. PMID:25838618

  4. 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

  5. Interaction between resistin and adiponectin in the proliferation of rat vascular smooth muscle cells.

    PubMed

    Hirai, Hiroyuki; Satoh, Hiroaki; Kudoh, Akihiro; Watanabe, Tsuyoshi

    2013-02-01

    We investigated the effect between resistin and adiponectin on the proliferation of vascular smooth muscle cells (VSMCs). We confirmed that resistin significantly increases the number of rat VSMCs as well as thymidine incorporation with them, whereas adiponectin diminishes resistin-induced cell proliferation. Resistin significantly increased p42/44 mitogen-activated protein kinase (MAPK) phosphorylation within rat VSMCs, whereas adiponectin inhibited resistin-induced MAPK phosphorylation. Moreover, resistin significantly increased c-fos expression, whereas adiponectin suppressed resistin-induced c-fos expression. Cell cycle progression is a tightly controlled event that is negatively regulated by cyclin-dependent kinases inhibitors (CDKIs) such as p53, p21, and p27. Resistin significantly decreased the expression of these CDKIs, whereas adiponectin restored the resistin-induced decrease in CDKIs expression. These effects were abolished in the MAPK inhibitors. In conclusion, resistin plays a role in the development of atherosclerosis, whereas adiponectin may be an important in its prevention in insulin-resistant patients. PMID:23267839

  6. 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

  7. Neuropeptide B and W regulate leptin and resistin secretion, and stimulate lipolysis in isolated rat adipocytes.

    PubMed

    Skrzypski, Marek; Pruszyńska-Oszmałek, Ewa; Ruciński, Marcin; Szczepankiewicz, Dawid; Sassek, Maciej; Wojciechowicz, Tatiana; Kaczmarek, Przemysław; Kołodziejski, Paweł A; Strowski, Mathias Z; Malendowicz, Ludwik K; Nowak, Krzysztof W

    2012-06-10

    Neuropeptide B (NPB) and W (NPW) regulate food intake and energy homeostasis in humans via two G-protein-coupled receptor subtypes, termed as GPR7 and GPR8. Rodents express GPR7 only. In animals, NPW decreases insulin and leptin levels, whereas the deletion of either NPB or GPR7 leads to obesity and hyperphagia. Metabolic and endocrine in vitro activities of NPW/NPB in adipocytes are unknown. We therefore characterize the effects of NPB and NPW on the secretion and expression of leptin and resistin, and on lipolysis, using rat adipocytes. Isolated rat adipocytes express GPR7 mRNA. NPB and NPW are expressed in macrophages and preadipocytes but are absent in mature adipocytes. Both, NPB and NPW reduce the secretion and expression of leptin from isolated rat adipocytes. NPB stimulates the secretion and expression of resistin, whereas both, NPB and NPW increase lipolysis. Our study demonstrates for the first time that NPB and NPW regulate the expression and secretion of leptin and resistin, and increase lipolysis in isolated rat adipocytes. These effects are presumably mediated via GPR7. The increase of resistin secretion, stimulation of lipolysis and the decrease of leptin secretion may represent mechanisms, through which NPB and NPW can affect glucose and lipid homeostasis, and food intake in rodents. PMID:22484289

  8. The effects of acute exercise on serum adiponectin and resistin levels and their relation to insulin sensitivity in overweight males.

    PubMed

    Jamurtas, A Z; Theocharis, V; Koukoulis, G; Stakias, N; Fatouros, I G; Kouretas, D; Koutedakis, Y

    2006-05-01

    The purpose of this study was to investigate the effects of a submaximal aerobic exercise bout on adiponectin and resistin levels as well as insulin sensitivity, until 48 h post-exercise in healthy overweight males. Nine subjects performed an exercise bout at an intensity corresponding to approximately 65% of their maximal oxygen consumption for 45 min. Adiponectin, resistin, cortisol, insulin, glucose and insulin sensitivity were measured prior to exercise, immediately after exercise as well as 24 and 48 h after exercise. Data were analyzed using repeated measures ANOVA while Pearson's correlations were performed to identify possible relationship among the assessed variables. There were no significant differences for adiponectin (microg ml(-1)) [pre, 3.61(0.73); post, 3.15(0.43); 24 h, 3.15(0.81); 48 h, 3.37(0.76)] or resistin (ng ml(-1)) [pre, 0.19(0.03); post, 0.13(0.03); 24 h, 0.23(0.04); 48 h, 0.23(0.03)] across time. Insulin sensitivity increased and insulin concentration decreased significantly only immediately after exercise. Furthermore, no significant correlations were observed among the variables assessed except for the expected between insulin level and insulin sensitivity. These results indicate that a submaximal aerobic workout does not result in significant changes in adiponectin and resistin up to 48 h post-exercise. Furthermore, it appears that adiponectin or resistin is not associated with insulin sensitivity. PMID:16525810

  9. 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

  10. Leptin, adiponectin and serotonin levels in lean and obese dogs

    PubMed Central

    2014-01-01

    Background Serotonin (5-hydroytryptamine or 5HT) is associated with numerous behavioral and psychological factors and is a biochemical marker of mood. 5HT is involved in the hypothalamic regulation of energy consumption. 5HT controls appetite in the central nerve system (CNS) and stimulates intestinal mobility. There are few studies looking at the role of 5HT and the relationship between peripheral circulating serotonin and obesity. The aim of this study was to find any differences in leptin, adiponectin, and 5HT between lean and obese dogs and to identify correlations among these factors. Results Leptin, triglyceride (TG) and cholesterol levels were higher in the obese group (all p < 0.01). Adiponectin and 5HT levels were higher in the lean group compared to the obese group (p < 0.01). Leptin (r = 0.628, p < 0.01), TG (r = 0.491, p < 0.01) and cholesterol (r = 0.419, p < 0.01) were positively correlated with body condition score (BCS), and adiponectin (r = -0.446, p < 0.01) and 5HT (r = -0.490, p < 0.01) were negatively correlated with BCS. Leptin was negatively correlated with adiponectin (r = -0.294, p < 0.01) and 5HT (r = -0.343, p < 0.01). 5HT was negatively correlated with leptin (r = -0.343, p < 0.01), TG (r = -0.268, p < 0.05) and cholesterol (r = -0.357, p < 0.05). Conclusions 5HT is an important appetite control neurotransmitter, but there are limited studies for 5HT levels related to obesity in dogs. To the best of our knowledge, this is the first study to evaluate peripheral 5HT levels in obese dogs. From this research, we can assume that 5HT may be correlated with canine obesity. Further studies will be needed to further elucidate the role of low serum 5HT levels in canine obesity. PMID:24886049

  11. 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.

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

    PubMed Central

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

    2016-01-01

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

  13. Differential effects of leptin on adiponectin expression with weight gain versus obesity

    PubMed Central

    Singh, Prachi; Sharma, Pragya; Sahakyan, Karine R.; Davison, Diane E.; Sert-Kuniyoshi, Fatima H; Romero-Corral, Abel; Swain, James M.; Jensen, Michael D.; Lopez-Jimenez, Francisco; Kara, Tomas; Somers, Virend K.

    2015-01-01

    Background/Objective Adiponectin exerts beneficial effects by reducing inflammation, and improving lipid metabolism and insulin-sensitivity. Although adiponectin is lower in obese individuals, whether weight gain reduces adiponectin expression in humans is controversial. We sought to investigate the role of weight gain, and consequent changes in leptin, on altering adiponectin expression in humans. Methods/Results Forty four normal-weight healthy subjects were recruited (mean age 29 years; 14 women) and randomized to either gain 5% of body weight by 8-weeks of overfeeding (n=34) or maintain weight (n=10). Modest weight gain of 3.8 ± 1.2 kg resulted in increased adiponectin (p=0.03) while weight maintenance resulted in no changes in adiponectin. Further, changes in adiponectin correlated positively with changes in leptin (p=0.0085). In-vitro experiments using differentiated human white preadipocytes showed that leptin increased adiponectin mRNA and protein expression, while a leptin-antagonist had opposite effects. To understand the role of leptin in established obesity, we compared adipose tissue samples obtained from normal weight versus obese subjects. We noted, first, that leptin activated cellular signaling pathways and increased adiponectin mRNA in adipose tissue from normal-weight participants, but did not do so in adipose tissue from obese participants; and second, that obese subjects had increased caveolin-1 expression, which attenuates leptin-dependent increases in adiponectin. Conclusions Modest weight gain in healthy individuals is associated with increases in adiponectin, which correlate positively with changes in leptin. In-vitro, leptin induces adiponectin expression which is attenuated by increased caveolin-1 expression. Additionally, adipose tissue from obese subjects shows increased caveolin-1 expression, and impaired leptin signaling. This leptin signal impairment may prevent concordant increases in adiponectin in obese subjects despite their

  14. Leptin and Adiponectin in the HIV Associated Metabolic Syndrome: Physiologic and Therapeutic Implications

    PubMed Central

    Tsiodras, Sotirios; Mantzoros, Christos

    2006-01-01

    Leptin and adiponectin represent two newly discovered adipose tissue derived hormones with important roles in energy homeostasis and insulin resistance. Their interrelations with the manifestations of the HIV associated metabolic syndrome and specific somatomorphic changes i.e. fat redistribution is reviewed. A synopsis of published studies is presented and the potential role of leptin and adiponectin is discussed. We have described an association of the HIV metabolic syndrome with a state of reduced insulin sensitivity due to adiponectin deficiency. The metabolic syndrome is also accompanied by leptin deficiency in lipoatrophic subjects and possibly by a leptin resistance state in lipohypertrophic patients. Adiponectin and / or leptin therapy in a manner similar to other leptin deficiency states may assist in the future management of such patients. PMID:17183414

  15. Association of plasma adiponectin and leptin levels with the development and progression of ovarian cancer

    PubMed Central

    Jin, Jing Hui; Kim, Hyun-Jung; Kim, Chan Young; Kim, Yun Hwan; Ju, Woong

    2016-01-01

    Objective Decreased adiponectin and increased leptin plasma concentrations are believed to be associated with the occurrence and progression of cancers such as endometrial cancer and breast cancer. The aim of this study was to explore the association of plasma adiponectin and leptin levels with the development and progression of ovarian cancer. Methods For patients with ovarian cancer and the control group, adiponectin and leptin levels were measured; anthropometric data were obtained during a chart review. Statistical comparisons between groups were analyzed using the Student's t-test; correlations were confirmed using the Pearson correlation. Results The mean adiponectin and leptin concentrations in patients with ovarian cancer were lower than those of the control group (8.25 vs. 11.44 µg/mL, respectively; P=0.026) (7.09 vs. 15.4 ng/mL, respectively; P=0.001). However, there was no significant difference in adiponectin and leptin levels between early-stage (I/II) and advanced-stage (III/IV) disease (P=0.078). Conclusion Compared with other gynecological cancers, the level of adiponectin and leptin were decreased in ovarian cancer that may have some diagnostic value; additional study to elucidate the function of these two hormones in the development of ovarian carcinogenesis is necessitated. PMID:27462594

  16. Adiponectin Isoforms and Leptin Impact on Rheumatoid Adipose Mesenchymal Stem Cells Function

    PubMed Central

    Skalska, Urszula; Kontny, Ewa

    2016-01-01

    Adiponectin and leptin have recently emerged as potential risk factors in rheumatoid arthritis (RA) pathogenesis. In this study we evaluated the effects of adiponectin and leptin on immunomodulatory function of adipose mesenchymal stem cells (ASCs) derived from infrapatellar fat pad of RA patients. ASCs were stimulated with leptin, low molecular weight (LMW) and high/middle molecular weight (HMW/MMW) adiponectin isoforms. The secretory activity of ASCs and their effect on rheumatoid synovial fibroblasts (RA-FLS) and peripheral blood mononuclear cells (PBMCs) from healthy donors have been analysed. RA-ASCs secreted spontaneously TGFβ, IL-6, IL-1Ra, PGE2, IL-8, and VEGF. Secretion of all these factors was considerably upregulated by HMW/MMW adiponectin, but not by LMW adiponectin and leptin. Stimulation with HMW/MMW adiponectin partially abolished proproliferative effect of ASC-derived soluble factors on RA-FLS but did not affect IL-6 secretion in FLS cultures. ASCs pretreated with HMW/MMW adiponectin maintained their anti-inflammatory function towards PBMCs, which was manifested by moderate PBMCs proliferation inhibition and IL-10 secretion induction. We have proved that HMW/MMW adiponectin stimulates secretory potential of rheumatoid ASCs but does not exert strong impact on ASCs function towards RA-FLS and PBMCs. PMID:26681953

  17. Lack of evidence for intermolecular epistatic interactions between adiponectin and resistin gene polymorphisms in Malaysian male subjects

    PubMed Central

    Lau, Cia-Hin; Muniandy, Sekaran

    2012-01-01

    Epistasis (gene-gene interaction) is a ubiquitous component of the genetic architecture of complex traits such as susceptibility to common human diseases. Given the strong negative correlation between circulating adiponectin and resistin levels, the potential intermolecular epistatic interactions between ADIPOQ (SNP+45T > G, SNP+276G > T, SNP+639T > C and SNP+1212A > G) and RETN (SNP-420C > G and SNP+299G > A) gene polymorphisms in the genetic risk underlying type 2 diabetes (T2DM) and metabolic syndrome (MS) were assessed. The potential mutual influence of the ADIPOQ and RETN genes on their adipokine levels was also examined. The rare homozygous genotype (risk alleles) of SNP-420C > G at the RETN locus tended to be co-inherited together with the common homozygous genotypes (protective alleles) of SNP+639T > C and SNP+1212A > G at the ADIPOQ locus. Despite the close structural relationship between the ADIPOQ and RETN genes, there was no evidence of an intermolecular epistatic interaction between these genes. There was also no reciprocal effect of the ADIPOQ and RETN genes on their adipokine levels, i.e., ADIPOQ did not affect resistin levels nor did RETN affect adiponectin levels. The possible influence of the ADIPOQ gene on RETN expression warrants further investigation. PMID:22481872

  18. 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

  19. 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

  20. Leptin Production by Encapsulated Adipocytes Increases Brown Fat, Decreases Resistin, and Improves Glucose Intolerance in Obese Mice.

    PubMed

    DiSilvestro, David J; Melgar-Bermudez, Emiliano; Yasmeen, Rumana; Fadda, Paolo; Lee, L James; Kalyanasundaram, Anuradha; Gilor, Chen L; Ziouzenkova, Ouliana

    2016-01-01

    The neuroendocrine effects of leptin on metabolism hold promise to be translated into a complementary therapy to traditional insulin therapy for diabetes and obesity. However, injections of leptin can provoke inflammation. We tested the effects of leptin, produced in the physiological adipocyte location, on metabolism in mouse models of genetic and dietary obesity. We generated 3T3-L1 adipocytes constitutively secreting leptin and encapsulated them in a poly-L-lysine membrane, which protects the cells from immune rejection. Ob/ob mice (OB) were injected with capsules containing no cells (empty, OB[Emp]), adipocytes (OB[3T3]), or adipocytes overexpressing leptin (OB[Lep]) into both visceral fat depots. Leptin was found in the plasma of OB[Lep], but not OB[Emp] and OB[3T3] mice at the end of treatment (72 days). The OB[Lep] and OB[3T3] mice have transiently suppressed appetite and weight loss compared to OB[Emp]. Only OB[Lep] mice have greater brown fat mass, metabolic rate, and reduced resistin plasma levels compared to OB[Emp]. Glucose tolerance was markedly better in OB[Lep] vs. OB[Emp] and OB[3T3] mice as well as in wild type mice with high-fat diet-induced obesity and insulin resistance treated with encapsulated leptin-producing adipocytes. Our proof-of-principle study provides evidence of long-term improvement of glucose tolerance with encapsulated adipocytes producing leptin. PMID:27055280

  1. Leptin Production by Encapsulated Adipocytes Increases Brown Fat, Decreases Resistin, and Improves Glucose Intolerance in Obese Mice

    PubMed Central

    DiSilvestro, David J.; Melgar-Bermudez, Emiliano; Yasmeen, Rumana; Fadda, Paolo; Lee, L. James; Kalyanasundaram, Anuradha; Gilor, Chen L.; Ziouzenkova, Ouliana

    2016-01-01

    The neuroendocrine effects of leptin on metabolism hold promise to be translated into a complementary therapy to traditional insulin therapy for diabetes and obesity. However, injections of leptin can provoke inflammation. We tested the effects of leptin, produced in the physiological adipocyte location, on metabolism in mouse models of genetic and dietary obesity. We generated 3T3-L1 adipocytes constitutively secreting leptin and encapsulated them in a poly-L-lysine membrane, which protects the cells from immune rejection. Ob/ob mice (OB) were injected with capsules containing no cells (empty, OB[Emp]), adipocytes (OB[3T3]), or adipocytes overexpressing leptin (OB[Lep]) into both visceral fat depots. Leptin was found in the plasma of OB[Lep], but not OB[Emp] and OB[3T3] mice at the end of treatment (72 days). The OB[Lep] and OB[3T3] mice have transiently suppressed appetite and weight loss compared to OB[Emp]. Only OB[Lep] mice have greater brown fat mass, metabolic rate, and reduced resistin plasma levels compared to OB[Emp]. Glucose tolerance was markedly better in OB[Lep] vs. OB[Emp] and OB[3T3] mice as well as in wild type mice with high-fat diet-induced obesity and insulin resistance treated with encapsulated leptin-producing adipocytes. Our proof-of-principle study provides evidence of long-term improvement of glucose tolerance with encapsulated adipocytes producing leptin. PMID:27055280

  2. Novel adiponectin-resistin (AR) and insulin resistance (IRAR) indexes are useful integrated diagnostic biomarkers for insulin resistance, type 2 diabetes and metabolic syndrome: a case control study

    PubMed Central

    2011-01-01

    Background Adiponectin and resistin are adipokines which modulate insulin action, energy, glucose and lipid homeostasis. Meta-analyses showed that hypoadiponectinemia and hyperresistinemia are strongly associated with increased risk of insulin resistance, type 2 diabetes (T2DM), metabolic syndrome (MS) and cardiovascular disease. The aim of this study was to propose a novel adiponectin-resistin (AR) index by taking into account both adiponectin and resistin levels to povide a better indicator of the metabolic homeostasis and metabolic disorders. In addition, a novel insulin resistance (IRAR) index was proposed by integration of the AR index into an existing insulin resistance index to provide an improved diagnostic biomarker of insulin sensitivity. Methods In this case control study, anthropometric clinical and metabolic parameters including fasting serum total adiponectin and resistin levels were determined in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS) whose ages ranged between 40-70 years old. Significant differences in continuous variables among subject groups were confirmed by ANCOVA or MANCOVA test using 1,000 stratified bootstrap samples with bias corrected and accelerated (BCa) 95% CI. Spearman's rho rank correlation test was used to test the correlation between two variables. Results The AR index was formulated as 1+log10(R0)-log10(A0). The AR index was more strongly associated with increased risk of T2DM and MS than hypoadiponectinemia and hyperresistinemia alone. The AR index was more strongly correlated with the insulin resistance indexes and key metabolic endpoints of T2DM and MS than adiponectin and resistin levels alone. The AR index was also correlated with a higher number of MS components than adiponectin and resistin levels alone. The IRAR index was formulated as log10(I0G0)+log10(I0G0)log10(R0/A0). The normal reference range of the IRAR index for insulin sensitive individuals was between 3.265 and

  3. Novel Adipokines, High Molecular Weight Adiponectin and Resistin, are Associated with Outcomes following Lower Extremity Revascularization with Autogenous Vein

    PubMed Central

    Owens, Christopher D.; Kim, Ji Min; Hevelone, Nathanael; Hamdan, Allen; Raffetto, Joseph D.; Creager, Mark A.; Conte, Michael S.

    2010-01-01

    Objective A significant portion of patients undergoing lower extremity bypass surgery (LEB) for peripheral arterial disease (PAD) will have cardiovascular or graft-related events. It has been previously demonstrated that systemic inflammation is associated with PAD and its clinical outcomes. We hypothesized that serum biomarkers of insulin resistance and inflammation would identify a sub-group at elevated risk for graft failure, limb loss, and mortality. Methods This was a prospective longitudinal study of patients (N=225) undergoing LEB using autogenous vein. Baseline blood samples were obtained prior to surgery in the fasting state. High-sensitivity C-reactive protein (hsCRP) and the adipokines resistin and high-molecular weight adiponectin (HMWA) were measured by ELISA. Median follow-up was 893 days. The major endpoints of primary patency (PP) and amputation free survival (AFS) were examined using multivariable methods. Endpoints were screened against biomarkers and patient characteristics for univariate associations. Promising explanatory variables (P < 0.1) were included in multivariable Cox proportional hazard models. Results The mean age of subjects was 67.6 years; 71.6% were male and 87.1% were Caucasian. One-hundred and thirty-three (59.1%) subjects underwent bypass for critical limb ischemia (CLI) and 73 (32.4%) had tissue loss. Patients with CLI and diabetes demonstrated elevated resistin and hsCRP levels. HMWA levels correlated with CLI and with a measure of insulin resistance (HOMA-IR) but not with clinical diabetes. Baseline biomarkers were higher in those presenting with tissue loss and in patients with post-operative events (mortality, limb loss). After multivariable analysis (including CLI, diabetes, age, estimated glomerular filtration rate (eGFR), adiponectin, resistin, and CRP), resistin (HR 1.75, 95% CI 1.07 to 2.85, P=0.025) and CRP (HR 2.39, 95% CI 1.30 to 4.39, P=0.005) were independently predictive of reduced AFS. However, only resistin

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

    PubMed

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

    2014-01-25

    Obesity is characterised by hyperleptinaemia and hypoadiponectinaemia and these metabolic abnormalities may contribute to the progression of several obesity-associated cancers including oesophageal adenocarcinoma (OAC). We have examined the effects of leptin and adiponectin on OE33 OAC cells. Leptin stimulated proliferation, invasion and migration and inhibited apoptosis in a STAT3-dependant manner. Leptin-stimulated MMP-2 secretion in a partly STAT3-dependent manner and MMP-9 secretion via a STAT3-independent pathway. Adiponectin inhibited leptin-induced proliferation, migration, invasion, MMP secretion and reduced the anti-apoptotic effects: these effects of adiponectin were ameliorated by both a non-specific tyrosine phosphatase inhibitor and a specific PTP1B inhibitor. Adiponectin reduced leptin-stimulated JAK2 activation and STAT3 transcriptional activity in a PTP1B-sensitive manner and adiponectin increased both PTP1B protein and activity. We conclude that adiponectin restrains leptin-induced signalling and pro-carcinogenic behaviour by inhibiting the early events in leptin-induced signal transduction by activating PTP1B. Relative adiponectin deficiency in obesity may contribute to the promotion of OAC. PMID:23994026

  5. Elevated resistin levels induce central leptin resistance and increased atherosclerotic progression in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Resistin was originally identified as an adipocyte-derived factor upregulated during obesity and as a contributor to obesity-associated insulin resistance. Clinically, resistin has also been implicated in cardiovascular disease in a number of different patient populations. Our aim was to simultaneou...

  6. Common genetic variation in adiponectin, leptin, and leptin receptor and association with breast cancer subtypes

    PubMed Central

    Nyante, Sarah J.; Gammon, Marilie D.; Kaufman, Jay S.; Bensen, Jeannette T.; Lin, Dan Yu; Barnholtz-Sloan, Jill S.; Hu, Yijuan; He, Qianchuan; Luo, Jingchun; Millikan, Robert C.

    2012-01-01

    Adipocytokines are produced by visceral fat, and levels may be associated with breast cancer risk. We investigated whether single nucleotide polymorphisms (SNPs) in adipocytokine genes adiponectin (ADIPOQ), leptin (LEP), and the leptin receptor (LEPR) were associated with basal-like or luminal A breast cancer subtypes. 104 candidate and tag SNPs were genotyped in 1776 of 2022 controls and 1972 (200 basal-like, 679 luminal A) of 2311 cases from the Carolina Breast Cancer Study (CBCS), a population-based case–control study of whites and African Americans. Breast cancer molecular subtypes were determined by immunohistochemistry. Genotype odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Haplotype ORs and 95% CIs were estimated using Hapstat. Interactions with waist-hip ratio were evaluated using a multiplicative interaction term. Ancestry was estimated from 144 ancestry informative markers (AIMs), and included in models to control for population stratification. Candidate SNPs LEPR K109R (rs1137100) and LEPR Q223R (rs1137101) were positively associated with luminal A breast cancer, whereas ADIPOQ +45 T/G (rs2241766), ADIPOQ +276 G/T (rs1501299), and LEPR K656N (rs8129183) were not associated with either subtype. Few patterns were observed among tag SNPs, with the exception of 3 LEPR SNPs (rs17412175, rs9436746, and rs9436748) that were in moderate LD and inversely associated with basal-like breast cancer. However, no SNP associations were statistically significant after adjustment for multiple comparisons. Haplotypes in LEP and LEPR were associated with both basal-like and luminal A subtypes. There was no evidence of interaction with waist-hip ratio. Data suggest associations between LEPR candidate SNPs and luminal A breast cancer in the CBCS and LEPR intron 2 tag SNPs and basal-like breast cancer. Replication in additional studies where breast cancer subtypes have been defined is necessary to confirm these

  7. Common genetic variation in adiponectin, leptin, and leptin receptor and association with breast cancer subtypes.

    PubMed

    Nyante, Sarah J; Gammon, Marilie D; Kaufman, Jay S; Bensen, Jeannette T; Lin, Dan Yu; Barnholtz-Sloan, Jill S; Hu, Yijuan; He, Qianchuan; Luo, Jingchun; Millikan, Robert C

    2011-09-01

    Adipocytokines are produced by visceral fat, and levels may be associated with breast cancer risk. We investigated whether single nucleotide polymorphisms (SNPs) in adipocytokine genes adiponectin (ADIPOQ), leptin (LEP), and the leptin receptor (LEPR) were associated with basal-like or luminal A breast cancer subtypes. 104 candidate and tag SNPs were genotyped in 1776 of 2022 controls and 1972 (200 basal-like, 679 luminal A) of 2311 cases from the Carolina Breast Cancer Study (CBCS), a population-based case-control study of whites and African Americans. Breast cancer molecular subtypes were determined by immunohistochemistry. Genotype odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Haplotype ORs and 95% CIs were estimated using Hapstat. Interactions with waist-hip ratio were evaluated using a multiplicative interaction term. Ancestry was estimated from 144 ancestry informative markers (AIMs), and included in models to control for population stratification. Candidate SNPs LEPR K109R (rs1137100) and LEPR Q223R (rs1137101) were positively associated with luminal A breast cancer, whereas ADIPOQ +45 T/G (rs2241766), ADIPOQ +276 G/T (rs1501299), and LEPR K656N (rs8129183) were not associated with either subtype. Few patterns were observed among tag SNPs, with the exception of 3 LEPR SNPs (rs17412175, rs9436746, and rs9436748) that were in moderate LD and inversely associated with basal-like breast cancer. However, no SNP associations were statistically significant after adjustment for multiple comparisons. Haplotypes in LEP and LEPR were associated with both basal-like and luminal A subtypes. There was no evidence of interaction with waist-hip ratio. Data suggest associations between LEPR candidate SNPs and luminal A breast cancer in the CBCS and LEPR intron 2 tag SNPs and basal-like breast cancer. Replication in additional studies where breast cancer subtypes have been defined is necessary to confirm these

  8. 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

  9. Effects of a 6-month infliximab treatment on plasma levels of leptin and adiponectin in patients with rheumatoid arthritis.

    PubMed

    Derdemezis, Christos S; Filippatos, Theodosios D; Voulgari, Paraskevi V; Tselepis, Alexandros D; Drosos, Alexandros A; Kiortsis, Dimitrios N

    2009-10-01

    Patients with rheumatoid arthritis (RA) appear to have increased plasma levels of leptin and adiponectin. These adipokines may be implicated in the pathophysiology of RA. Tumour necrosis factor alpha (TNF-alpha) is a potential modulator of adipokines. The effects of long-term anti-TNF treatment on plasma levels of leptin and adiponectin are not clear. The aim of this study was to assess the effects of 6-month anti-TNF treatment (infliximab) on leptin and adiponectin plasma levels in RA patients. Thirty women with RA were included in the study. Patients with diabetes mellitus, any endocrine disorder or receiving any hypolipidemic or antidiabetic medication were not included. Thirty healthy age- and body mass index-matched women served as controls. Plasma levels of leptin and adiponectin were measured with enzyme immunoassay methods prior to and after the 6-month treatment with infliximab. Mean age and disease duration of patients were 51.8 +/- 14.4 and 12.2 +/- 6.7 years, respectively. Body weight did not change significantly over the 6-month period. Plasma levels of leptin and adiponectin were higher in patients than controls and did not change significantly after 6-month treatment. Interestingly, in the tertile of patients with the highest baseline adiponectin concentrations, adiponectin levels were significantly reduced (P < 0.05). Infliximab treatment did not change plasma levels of leptin and adiponectin after 6-month treatment in the whole study population. However, a reduction of adiponectin levels was observed in patients with higher baseline adiponectin levels. PMID:19563510

  10. The effect of cumulative endurance exercise on leptin and adiponectin and their role as markers to monitor training load.

    PubMed

    Voss, S C; Nikolovski, Z; Bourdon, P C; Alsayrafi, M; Schumacher, Y O

    2016-03-01

    Leptin and adiponectin play an essential role in energy metabolism. Leptin has also been proposed as a marker for monitoring training load. So far, no studies have investigated the variability of these hormones in athletes and how they are regulated during cumulative exercise. This study monitored leptin and adiponectin in 15 endurance athletes twice daily in the days before, during and after a 9-day simulated cycling stage race. Adiponectin significantly increased during the race (p = 0.001) and recovery periods (p = 0.002) when compared to the baseline, while leptin decreased significantly during the race (p < 0.0001) and returned to baseline levels during the recovery period. Intra-individual variability was substantially lower than inter-individual variability for both hormones (leptin 34.1 vs. 53.5%, adiponectin 19% vs. 37.2%). With regards to exercise, this study demonstrated that with sufficient, sustained energy expenditure, leptin concentrations can decrease within the first 24 hours. Under the investigated conditions there also appears to be an optimal leptin concentration which ensures stable energy homeostasis, as there was no significant decrease over the subsequent race days. In healthy endurance athletes the recovery of leptin takes 48-72 hours and may even show a supercompensation-like effect. For adiponectin, significant increases were observed within 5 days of commencing racing, with these elevated values failing to return to baseline levels after 3 days of recovery. Additionally, when using leptin and adiponectin to monitor training loads, establishing individual threshold values improves their sensitivity. PMID:26985130

  11. The effect of cumulative endurance exercise on leptin and adiponectin and their role as markers to monitor training load

    PubMed Central

    Nikolovski, Z; Bourdon, PC; Alsayrafi, M; Schumacher, YO

    2015-01-01

    Leptin and adiponectin play an essential role in energy metabolism. Leptin has also been proposed as a marker for monitoring training load. So far, no studies have investigated the variability of these hormones in athletes and how they are regulated during cumulative exercise. This study monitored leptin and adiponectin in 15 endurance athletes twice daily in the days before, during and after a 9-day simulated cycling stage race. Adiponectin significantly increased during the race (p = 0.001) and recovery periods (p = 0.002) when compared to the baseline, while leptin decreased significantly during the race (p < 0.0001) and returned to baseline levels during the recovery period. Intra-individual variability was substantially lower than inter-individual variability for both hormones (leptin 34.1 vs. 53.5%, adiponectin 19% vs. 37.2%). With regards to exercise, this study demonstrated that with sufficient, sustained energy expenditure, leptin concentrations can decrease within the first 24 hours. Under the investigated conditions there also appears to be an optimal leptin concentration which ensures stable energy homeostasis, as there was no significant decrease over the subsequent race days. In healthy endurance athletes the recovery of leptin takes 48-72 hours and may even show a supercompensation-like effect. For adiponectin, significant increases were observed within 5 days of commencing racing, with these elevated values failing to return to baseline levels after 3 days of recovery. Additionally, when using leptin and adiponectin to monitor training loads, establishing individual threshold values improves their sensitivity. PMID:26985130

  12. Resistin as a potential marker of renal disease in lupus nephritis.

    PubMed

    Hutcheson, J; Ye, Y; Han, J; Arriens, C; Saxena, R; Li, Q-Z; Mohan, C; Wu, T

    2015-03-01

    Systemic lupus erythematosus (SLE) and lupus nephritis (LN) have strong concomitance with cardiovascular disease that cannot be explained fully by typical risk factors. We examined the possibility that serum or urine expression of adipokines may act as biomarkers for LN, as these proteins have been associated previously with cardiovascular disease as well as SLE. Antibody arrays were performed on serum and urine from lupus patients and matched controls using a cross-sectional study design. From the initial array-based screening data of 15 adipokines, adiponectin, leptin and resistin were selected for validation by enzyme-linked immunosorbent assay (ELISA). Correlations were determined between adipokine expression levels and measures of disease activity or lupus nephritis. The expression of adiponectin and resistin was increased in both sera and urine from LN patients, while leptin was increased in LN patient sera, compared to matched controls. Serum resistin, but not urine resistin, was correlated with measures of renal dysfunction in LN. Serum resistin expression may be useful as a marker of renal dysfunction in patients with LN, although longitudinal studies are warranted. Further studies are necessary to determine if resistin has functional consequences in LN. PMID:25345756

  13. Resistin as a potential marker of renal disease in lupus nephritis

    PubMed Central

    Hutcheson, J; Ye, Y; Han, J; Arriens, C; Saxena, R; Li, Q-Z; Mohan, C; Wu, T

    2015-01-01

    Systemic lupus erythematosus (SLE) and lupus nephritis (LN) have strong concomitance with cardiovascular disease that cannot be explained fully by typical risk factors. We examined the possibility that serum or urine expression of adipokines may act as biomarkers for LN, as these proteins have been associated previously with cardiovascular disease as well as SLE. Antibody arrays were performed on serum and urine from lupus patients and matched controls using a cross-sectional study design. From the initial array-based screening data of 15 adipokines, adiponectin, leptin and resistin were selected for validation by enzyme-linked immunosorbent assay (ELISA). Correlations were determined between adipokine expression levels and measures of disease activity or lupus nephritis. The expression of adiponectin and resistin was increased in both sera and urine from LN patients, while leptin was increased in LN patient sera, compared to matched controls. Serum resistin, but not urine resistin, was correlated with measures of renal dysfunction in LN. Serum resistin expression may be useful as a marker of renal dysfunction in patients with LN, although longitudinal studies are warranted. Further studies are necessary to determine if resistin has functional consequences in LN. PMID:25345756

  14. 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

  15. Fish oil N-3 fatty acids increase adiponectin and decrease leptin levels in patients with systemic lupus erythematosus.

    PubMed

    Lozovoy, Marcell Alysson Batisti; Simão, Andréa Name Colado; Morimoto, Helena Kaminami; Scavuzzi, Bruna Miglioranza; Iriyoda, Tathiana Veiga Mayumi; Reiche, Edna Maria Vissoci; Cecchini, Rubens; Dichi, Isaias

    2015-02-01

    Cardiovascular disease (CVD) has emerged as an important cause of death in patients with systemic lupus erythematosus (SLE). Reduced adiponectin and elevated leptin levels may contribute to CVD in SLE patients. The purpose of this study was to verify the effects of fish oil (FO) on adiponectin and leptin in patients with SLE. Biochemical and disease activity analysis were performed. Patients with SLE were divided in two groups: patients who used fish oil for four months and patients who did not use fish oil. Patients with SLE who used FO had a significant decrease in SLE disease activity index (SLEDAI) score (p ˂ 0.023) in relation to baseline. SLE patients who used fish oil had increased adiponectin levels (p ˂ 0.026) and decreased leptin levels (p ˂ 0.024) compared to baseline values, whereas there were no differences in adiponectin and leptin levels in patients with SLE who did not use fish oil. In conclusion, the findings of increased serum adiponectin an decreased leptin levels after 120 days in the fish oil group, reinforce the importance of evaluating prospective studies of fish and fish oil fish ingestion on these adipokines in an attempt to decrease cardiovascular risk factors in patients with SLE. PMID:25690094

  16. Fish Oil N-3 Fatty Acids Increase Adiponectin and Decrease Leptin Levels in Patients with Systemic Lupus Erythematosus

    PubMed Central

    Lozovoy, Marcell Alysson Batisti; Colado Simão, Andréa Name; Morimoto, Helena Kaminami; Scavuzzi, Bruna Miglioranza; Iriyoda, Tathiana Veiga Mayumi; Reiche, Edna Maria Vissoci; Cecchini, Rubens; Dichi, Isaias

    2015-01-01

    Cardiovascular disease (CVD) has emerged as an important cause of death in patients with systemic lupus erythematosus (SLE). Reduced adiponectin and elevated leptin levels may contribute to CVD in SLE patients. The purpose of this study was to verify the effects of fish oil (FO) on adiponectin and leptin in patients with SLE. Biochemical and disease activity analysis were performed. Patients with SLE were divided in two groups: patients who used fish oil for four months and patients who did not use fish oil. Patients with SLE who used FO had a significant decrease in SLE disease activity index (SLEDAI) score (p ˂ 0.023) in relation to baseline. SLE patients who used fish oil had increased adiponectin levels (p ˂ 0.026) and decreased leptin levels (p ˂ 0.024) compared to baseline values, whereas there were no differences in adiponectin and leptin levels in patients with SLE who did not use fish oil. In conclusion, the findings of increased serum adiponectin an decreased leptin levels after 120 days in the fish oil group, reinforce the importance of evaluating prospective studies of fish and fish oil fish ingestion on these adipokines in an attempt to decrease cardiovascular risk factors in patients with SLE. PMID:25690094

  17. Repeated electroacupuncture in obese Zucker diabetic fatty rats: adiponectin and leptin in serum and adipose tissue.

    PubMed

    Peplow, Philip V

    2015-04-01

    Fasted, male, obese, Zucker, diabetic fatty rats aged 10-16 weeks were anesthetized with 1% halothane in nitrous oxide-oxygen (3:1) on alternate weekdays over 2 weeks. Group 1 (n = 4) did not receive electroacupuncture (controls); Group 2 (n = 4) received electroacupuncture using the Zhongwan and the Guanyuan acupoints; Group 3 (n = 4) received electroacupuncture using the bilateral Zusanli acupoints; Group 4 (n = 6) received neither halothane in nitrous oxide:oxygen nor electroacupuncture. At the end of study, animals were injected with sodium pentobarbitone (60 mg/mL, i.p.), and blood and white adipose tissue were collected. Analysis of variance and Duncan's tests showed that the mean leptin in serum was significantly lower and the adiponectin:leptin ratio was significantly higher in Group 2 than in Group 1 (p < 0.05); for Group 4, the serum leptin was significantly higher than it was for Groups 1-3 (p < 0.05), and the adiponectin:leptin ratio was significantly lower than it was for Group 2 (p < 0.05). Similar changes occurred for the leptin levels in the pelvic adipose tissue. In addition, for Group 2, the mean serum insulin: glucose ratio was significantly higher than it was for Group 1 (p < 0.05); for Group 4 the mean serum insulin and insulin: glucose ratio were significantly higher than they were for Groups 1 and 3 (p < 0.05), but not Group 2 (p > 0.05). No significant differences in the serum or the adipose-tissue measurements between Groups 1 and 3 were observed (p > 0.05). PMID:25952122

  18. A 25 Year Prospective Study of Plasma Adiponectin and Leptin Concentrations and Prostate Cancer Risk and Survival

    PubMed Central

    Li, Haojie; Stampfer, Meir J.; Mucci, Lorelei; Rifai, Nader; Qiu, Weiliang; Kurth, Tobias; Ma, Jing

    2010-01-01

    Background Adipocytokines may mediate the association between adiposity and lethal prostate cancer outcomes. Methods In the Physicians’ Health Study, we prospectively examined the association of prediagnostic plasma concentrations of adiponectin and leptin with risk of developing incident prostate cancer (654 case diagnosed 1982-2000 and 644 age-matched controls) and, among cases, risk of dying from prostate cancer by 2007. Results Adiponectin concentrations were not associated with risk of overall prostate cancer. However, men with higher adiponectin concentrations had lower risk of developing high grade or lethal cancer (metastatic or fatal disease). The relative risk (95% confidence interval) comparing the highest to the lowest quintile (Q5 vs. Q1) was 0.25 (0.07-0.87; Ptrend=0.02) for lethal cancer. Among all the cases, higher adiponectin concentrations predicted lower prostate cancer-specific mortality (hazard ratio, HR Q5 vs. Q1=0.39; 0.17-0.85; Ptrend=0.02), independent of body mass index (BMI), plasma C-peptide (a marker of insulin secretion), leptin, clinical stage and tumor grade. This inverse association was apparent mainly among men whose BMI ≥25 kg/m2 (HR Q5 vs. Q1=0.10; 0.01-0.78; Ptrend=0.02), but not among men of normal weight (Ptrend=0.51). Although the correlation of leptin concentrations with BMI (r=0.58, P <0.001) was stronger than that of adiponectin (r=−0.17, P<0.001), leptin was unrelated to prostate cancer risk or mortality. Conclusion Higher prediagnostic adiponectin (but not leptin) concentrations predispose men to a lower risk of developing high grade prostate cancer and a lower risk of subsequently dying from the cancer, suggesting a mechanistic link between obesity and poor PCa outcome. PMID:19910504

  19. The Relationship Between Serum Adiponectin, Tumor Necrosis Factor−Alpha, Leptin Levels and Insulin Sensitivity in Childhood and Adolescent Obesity: Adiponectin is a Marker of Metabolic Syndrome

    PubMed Central

    Gönç, E. Nazlı; Özön, Z. Alev; Şen, Yaşar; Kandemir, Nurgün

    2009-01-01

    Objective: This study aimed (a) to investigate the relationship between the degree of obesity and serum adiponectin, tumor necrosis factor (TNF)−α, leptin, insulin levels and the lipid profile; (b) to clarify the relationship between insulin resistance/glucose tolerance and adipocytokine levels; and (c) to investigate the value of adipocytokine levels as a marker of metabolic syndrome (MS). Methods: We studied 151 obese children and adolescents (86 boys and 65 girls; mean age was 12.3±2.4 years). We defined obesity as a body−mass index (BMI) z−score more than 2 SD above the mean for age and sex. The control group consisted of 100 children (48 boys, 52 girls, mean age 12.4±2.5 years). Fasting glucose, insulin levels and lipid profiles were measured in all cases and controls after a 12−hour fast. Adiponectin, TNF−α, and leptin levels were measured in the subjects who participated in the adipocytokine branch of the study. An oral glucose tolerance test (OGTT) was also performed in all obese patients. Obese patients were grouped into three subgroups according to their glucose tolerance and insulin sensitivity assessment, and also according to whether they were grouped as MS or not. Results: Serum levels of total cholesterol, LDL and VLDL cholesterol, log triglyceride, insulin, leptin and TNF−α were higher, whereas HDL and square root adiponectin levels were lower in the obese group when compared with controls. Multiple regression analysis among BMI−z score, LDL, triglyceride, HOMA−IR, leptin and TNF−α as determinants of adiponectin revealed that BMI−z score was the only determinant for adiponectin (r:−0.45, p<0.0001). Adiponectin levels in hyperinsulinemic and impaired glucose tolerance groups (IGT) tended to be lower than in normoinsulinemic obese children, however, the difference was not significant. There was a weak negative correlation between adiponectin levels and increasing severity of insulin resistance (r=−0.23, p=0.005) in the

  20. Impact of maternal BMI and sampling strategy on the concentration of leptin, insulin, ghrelin and resistin in breast milk across a single feed: a longitudinal cohort study

    PubMed Central

    Andreas, Nicholas J; Hyde, Matthew J; Herbert, Bronwen R; Jeffries, Suzan; Santhakumaran, Shalini; Mandalia, Sundhiya; Holmes, Elaine; Modi, Neena

    2016-01-01

    Objectives We tested the hypothesis that there is a positive association between maternal body mass index (BMI) and the concentration of appetite-regulating hormones leptin, insulin, ghrelin and resistin in breast milk. We also aimed to describe the change in breast milk hormone concentration within each feed, and over time. Setting Mothers were recruited from the postpartum ward at a university hospital in London. Breast milk samples were collected at the participants’ homes. Participants We recruited 120 healthy, primiparous, breastfeeding mothers, aged over 18 years. Mothers who smoked, had multiple births or had diabetes were excluded. Foremilk and hindmilk samples were collected from 105 women at 1 week postpartum and 92 women at 3 months postpartum. Primary and secondary outcome measures We recorded maternal and infant anthropometric measurements at each sample collection and measured hormone concentrations using a multiplex assay. Results The concentration of leptin in foremilk correlated with maternal BMI at the time of sample collection, at 7 days (r=0.31, p=0.02) and 3 months postpartum (r=0.30, p=<0.00). Foremilk insulin correlated with maternal BMI at 3 months postpartum (r=0.22, p=0.04). Breast milk ghrelin and resistin were not correlated with maternal BMI. Ghrelin concentrations at 3 months postpartum were increased in foremilk compared with hindmilk (p=0.01). Concentrations of ghrelin were increased in hindmilk collected at 1  week postpartum compared with samples collected at 3 months postpartum (p=0.03). A trend towards decreased insulin concentrations in hindmilk was noted. Concentrations of leptin and resistin were not seen to alter over a feed. Conclusions A positive correlation between maternal BMI and foremilk leptin concentration at both time points studied, and foremilk insulin at 3 months postpartum was observed. This may have implications for infant appetite regulation and obesity risk. PMID:27388351

  1. Chronic Kidney Disease, Obesity, and Hypertension: The Role of Leptin and Adiponectin

    PubMed Central

    Tesauro, M.; Mascali, A.; Franzese, O.; Cipriani, S.; Cardillo, C.; Di Daniele, N.

    2012-01-01

    Chronic kidney disease is a major public health problem and characterized by a progressive loss in renal function over a period of months or years as defined by structural or functional abnormalities of the kidney. Several elements contribute to determine a progression of the kidney injury, inducing a worsening of renal damage and accelerating the decline of renal function: obesity and hypertension are two known factors of kidney progression. Remarkable improvements have been recently achieved in the study of the endocrine features of the adipose tissue and have been able to produce hormone-like peptides named adipokines or adipocytokines. Among these adipocytokines, which represent a link between obesity, hypertension, and chronic nephropathy, leptins and adiponectin appear to play an important role. Leptin not only is a prohypertension element (renal progression factor) through the activation sympathetic nervous, but also is able to induce prosclerotic effects directly on the kidney. In contrast, a decline of adiponectin levels has been shown to be related to a picture of hypertension: an endothelial dysfunction has been described as the main pathogenic mechanism responsible for this phenomenon. PMID:23320148

  2. Effects of individual and combined dietary weight loss and exercise interventions in postmenopausal women on adiponectin and leptin levels

    PubMed Central

    Abbenhardt, Clare; McTiernan, Anne; Alfano, Catherine M.; Wener, Mark H.; Campbell, Kristin L.; Duggan, Catherine; Foster-Schubert, Karen E.; Kong, Angela; Toriola, Adetunji T; Potter, John D.; Mason, Caitlin; Xiao, Liren; Blackburn, George L.; Bain, Carolyn; Ulrich, Cornelia M.

    2013-01-01

    Background Excess body weight and a sedentary lifestyle are associated with the development of several diseases, including cardiovascular disease, diabetes, and cancer in women. One proposed mechanism linking obesity to chronic diseases is an alteration in adipose-derived adiponectin and leptin levels. We investigated the effects of 12-month reduced calorie, weight loss and exercise interventions on adiponectin and leptin concentrations. Methods Overweight/obese postmenopausal women (n=439) were randomized as follows: 1) a reduced calorie, weight loss diet (diet; N=118); 2) moderate-to-vigorous intensity aerobic exercise (exercise; N=117); 3) a combination of a reduced calorie, weight loss diet and moderate-to-vigorous intensity aerobic exercise (diet+exercise; N=117); or 4) control (N=87). The reduced calorie diet had a 10% weight loss goal. The exercise intervention consisted of 45 minutes of moderate-to-vigorous aerobic activity 5 days/week. Adiponectin and leptin levels were measured at baseline and after 12 months of intervention using a radioimmunoassay. Results Adiponectin increased by 9.5 % in the diet group and 6.6 % in the diet+exercise group (both p≤0.0001 vs. control). Compared with controls, leptin decreased with all interventions (diet+exercise, −40.1%, p<0.0001; diet, −27.1%, p<0.0001; exercise, −12.7%, p=0.005). The results were not influenced by the baseline body mass index (BMI). The degree of weight loss was inversely associated with concentrations of adiponectin (diet, p-trend=0.0002; diet+exercise, p-trend=0.0005) and directly associated with leptin (diet, p-trend<0.0001; diet+exercise, p-trend<0.0001). Conclusion Weight loss through diet or diet+exercise increased adiponectin concentrations. Leptin concentrations decreased in all of the intervention groups, but the greatest reduction occurred with diet+exercise. Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin. PMID

  3. N-3 Polyunsaturated fatty acid therapy improves endothelial function and affects adiponectin and resistin balance in the first month after myocardial infarction

    PubMed Central

    Mizia-Stec, Katarzyna; Haberka, Maciej; Mizia, Magdalena; Chmiel, Artur; Gieszczyk, Klaudia; Lasota, Bartosz; Janowska, Joanna; Zahorska-Markiewicz, Barbara; Gąsior, Zbigniew

    2011-01-01

    Introduction N-3 Polyunsaturated fatty acids (n-3 PUFA) exert clinical beneficial effects in patients after acute myocardial infarction (AMI). However, their exact mechanisms of action are not well recognized yet. Our aim was to evaluate effects of early introduced n-3 PUFA supplementation on endothelial function and serum adipokine concentrations in patients with AMI. Material and methods Thirty-eight patients with AMI and successful coronary stent implantation were randomized to the study group (PUFA group: n = 19; standard therapy + PUFA 1 g daily) and the control group (control group: n = 19; standard therapy). The study group patients were given n-3 PUFA (Omacor 1 g daily) starting from the 3rd day of AMI. Ultrasound vascular indexes (flow-mediated dilatation [FMD], nitroglycerine-mediated dilation [NMD]) and serum concentrations of adiponectin and resistin (ELISA) were evaluated before and after 30 days of pharmacotherapy. Results Comparison of the mean delta values (baseline/after 30 days of therapy) between groups revealed significant differences for delta FMD (PUFA 7.6 ±12.4% vs. control –1.7 ±10.5%, p = 0.019) and delta resistin concentrations (PUFA 1.0 ±3.8pg/ml vs. control –1.6 ±2.9pg/ml, p = 0.028). Multiple linear regression analysis for all subjects revealed the n-3 PUFA supplementation (r = 10.933, p = 0.004) and waist circumference (r = –0.467, p = 0.01) as independent factors associated with delta FMD values (R-adjusted 0.29; p = 0.002). Conclusions Early and short-term n-3 PUFA supplementation in AMI with successful primary PCI and optimal pharmacotherapy improves endothelial function. However, increased resistin serum levels observed after 1-month n-3 PUFA supplementation merits further investigations. PMID:22291823

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

    PubMed

    Kim, Ki-Woong; Won, Yong Lim; Ko, Kyung Sun; Roh, Ji Won

    2014-06-01

    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 risk

  5. Omega-3 fatty acids: a review of the effects on adiponectin and leptin and potential implications for obesity management.

    PubMed

    Gray, B; Steyn, F; Davies, P S W; Vitetta, L

    2013-12-01

    An increase in adiposity is associated with altered levels of biologically active proteins. These include the hormones adiponectin and leptin. The marked change in circulating concentrations of these hormones in obesity has been associated with the development of insulin resistance and metabolic syndrome. Variations in dietary lipid consumption have also been shown to impact obesity. Specifically, omega-3 fatty acids have been correlated with the prevention of obesity and subsequent development of chronic disease sequalae. This review explores animal and human data relating to the effects of omega-3 fatty acids (marine lipids) on adiponectin and leptin, considering plausible mechanisms and potential implications for obesity management. Current evidence suggests a positive, dose-dependent relationship between omega-3 fatty acid intake and circulating levels of adiponectin. In obese subjects, this may translate into a reduced risk of developing cardiovascular disease, metabolic syndrome and diabetes. In non-obese subjects, omega-3 is observed to decrease circulating levels of leptin; however, omega-3-associated increases in leptin levels have been observed in obese subjects. This may pose benefits in the prevention of weight regain in these subjects following calorie restriction. PMID:24129365

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

    PubMed Central

    Motawi, Tarek; Salman, Tarek; Shaker, Olfat

    2015-01-01

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

  7. The effects of prolonged fasting on the levels of adiponectin, leptin, apelin, and omentin in pregnant women.

    PubMed

    Kiyak Caglayan, Emel; Engin-Ustun, Yaprak; Sari, Nagihan; Gocmen, Ayşe Yesim; Polat, M Fevzi

    2016-05-01

    The aim of the present study was to evaluate serum adiponectin, leptin, apelin and omentin levels to explore metabolic changes occurring during fasting in the month of Ramadan. The study was designed as a prospective study. The patients were divided into two groups, each comprising 20 patients: Group I, fasting pregnant women, and Group II, non-fasting pregnant women. The patients' age, parity, gestational week and body mass index were recorded. Adiponectin and omentin levels were significantly lower in fasting pregnant women (p < 0.001). When the two groups were compared in terms of serum leptin and apelin levels, both were found to be significantly higher in Group I than in Group II. The findings of the present study suggest that pregnant women who are willing to fast during 24-38 weeks' gestation should be informed about insulin resistance. PMID:26759187

  8. On-Statin Resistin, Leptin, and Risk of Recurrent Coronary Events After Hospitalization for an Acute Coronary Syndrome (from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Study).

    PubMed

    Khera, Amit V; Qamar, Arman; Murphy, Sabina A; Cannon, Christopher P; Sabatine, Marc S; Rader, Daniel J

    2015-09-01

    Resistin is an adipokine secreted by macrophages and inflammatory cells linked to insulin resistance and inflammation. Leptin is an adipokine regulator of appetite and obesity. Although circulating levels of both have been associated with atherosclerosis, few data have reported their relation to coronary events in the context of statin therapy. This study measured on-statin levels of both resistin and leptin through enzyme-linked immunosorbent assay in a nested case-control cohort (n = 176 cases with coronary death, myocardial infarction, or unstable angina pectoris observed in follow-up matched 1:1 to 176 controls) derived from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 study, a randomized controlled trial of atorvastatin 80 mg/day versus pravastatin 40 mg/day in patients with a recent acute coronary syndrome. Resistin demonstrated a moderate association with high-sensitivity C-reactive protein (hsCRP; Spearman rho = 0.25, p <0.0001). On-statin resistin levels were linked to recurrent coronary events in conditional logistic regression analysis adjusted for additional risk factors including hsCRP and history of diabetes (tertile 3 vs 1 adjusted odds ratio 2.08; 95% confidence interval [CI] 1.04 to 4.19). An additive risk was noted when patients were stratified by resistin and glycated hemoglobin levels. In contrast, leptin levels were associated with obesity, diabetes, triglycerides, and hsCRP (p <0.001 for each) but demonstrated no association with recurrent coronary events (tertile 3 vs 1 adjusted odds ratio 0.72; 95% CI 0.28 to 1.83). In conclusion, on-statin resistin, but not leptin, is an independent marker of residual risk for recurrent coronary events in patients after hospitalization for an acute coronary syndrome. PMID:26119654

  9. Serum Adiponectin and Leptin Concentrations in Relation to Body Fat Distribution, Hematological Indices and Lipid Profile in Humans

    PubMed Central

    Lubkowska, Anna; Radecka, Aleksandra; Bryczkowska, Iwona; Rotter, Iwona; Laszczyńska, Maria; Dudzińska, Wioleta

    2015-01-01

    The purpose of the study was to evaluate the relationship between serum adiponectin and leptin concentrations and body composition, hematological indices and lipid profile parameters in adults. The study involved 95 volunteers (BMI from 23.3 to 53 kg/m2). Anthropometric parameters were measured: body weight and height, waist and hip circumference, waist-to-hip ratio, body fat mass (BMF), subcutaneous and visceral fat mass (SFM, VFM), lean body mass (LBM), skeletal muscle mass (SMM). In serum we determined adiponectin and leptin concentrations, extracellular hemoglobin, total bilirubin, as well as lipid metabolism (TCh, HDL-Ch, LDL-Ch, TG). Mean adipokine levels were significantly higher in women (p ≤ 0.01), adiponectin significantly negatively correlated with body height and weight, systolic blood pressure and absolute LBM and SMM values. The same relation was observed for erythroid system indicators and lipid indicators. A positive correlation was exceptionally found between adiponectin and HDL-Ch. LEP negatively correlated with some percentage rates (%LBM, %SMM). Only in women, we observed a positive correlation between LEP and body weight, BMI and WHR. Studies on ADPN and the ADPN/LEP ratio as a valuable complementary diagnostic element in the prediction and prevention of cardiovascular diseases need to be continued. PMID:26389928

  10. Serum Adiponectin and Leptin Concentrations in Relation to Body Fat Distribution, Hematological Indices and Lipid Profile in Humans.

    PubMed

    Lubkowska, Anna; Radecka, Aleksandra; Bryczkowska, Iwona; Rotter, Iwona; Laszczyńska, Maria; Dudzińska, Wioleta

    2015-09-01

    The purpose of the study was to evaluate the relationship between serum adiponectin and leptin concentrations and body composition, hematological indices and lipid profile parameters in adults. The study involved 95 volunteers (BMI from 23.3 to 53 kg/m²). Anthropometric parameters were measured: body weight and height, waist and hip circumference, waist-to-hip ratio, body fat mass (BMF), subcutaneous and visceral fat mass (SFM, VFM), lean body mass (LBM), skeletal muscle mass (SMM). In serum we determined adiponectin and leptin concentrations, extracellular hemoglobin, total bilirubin, as well as lipid metabolism (TCh, HDL-Ch, LDL-Ch, TG). Mean adipokine levels were significantly higher in women (p ≤ 0.01), adiponectin significantly negatively correlated with body height and weight, systolic blood pressure and absolute LBM and SMM values. The same relation was observed for erythroid system indicators and lipid indicators. A positive correlation was exceptionally found between adiponectin and HDL-Ch. LEP negatively correlated with some percentage rates (%LBM, %SMM). Only in women, we observed a positive correlation between LEP and body weight, BMI and WHR. Studies on ADPN and the ADPN/LEP ratio as a valuable complementary diagnostic element in the prediction and prevention of cardiovascular diseases need to be continued. PMID:26389928

  11. Effects of body weight reduction on plasma leptin and adiponectin/leptin ratio in obese patients with type 1 diabetes mellitus.

    PubMed

    Musil, F; Blaha, V; Ticha, A; Hyspler, R; Haluzik, M; Lesna, J; Smahelova, A; Sobotka, L

    2015-01-01

    The aim of this study was to explore the changes in the adipokines leptin and adiponectin in obese patients with type 1 diabetes mellitus (T1DM) who underwent seven days of fasting and 21 days of low-calorie diet (LCD). The plasma leptin and adiponectin concentrations were measured in 14 obese patients with T1DM at baseline, immediately after 7 days of fasting, and after 21 days of LCD. 13 non-obese patients with T1DM were studied only after an overnight fasting. Bioimpedance technique was used for determination of body composition. Obese T1DM patients lost 6.0 kg (6.0; 6.8) (median, 25 %; 75 %) and decreased their fat tissue after fasting and LCD. Plasma leptin in obese T1DM was significantly higher than in non-obese T1DM patients: 9.10 (5.06; 25.89) vs. 1.71 (1.12; 7.08) microg . l(-1) and transiently decreased immediately after fasting: 3.45 microg . l(-1) (1.47; 7.00), (P<0.05). Adiponectin/leptin ratio in obese T1DM was significantly lower than in non-obese T1DM patients: 0.67 (0.57; 1.49) vs. 3.50 (2.46; 6.30) . 10(3) and transiently increased immediately after fasting: 2.22 (1.26; 3.24) . 10(3), (P<0.05). We conclude that obese patients with T1DM are characterized by hyperleptinemia that is reduced by prolonged fasting, but only slightly affected by low calorie diet. PMID:25317681

  12. Adiponectin, ghrelin, and leptin differentially influence human platelet and human vascular endothelial cell functions: implication in obesity-associated cardiovascular diseases.

    PubMed

    Elbatarny, Hisham S; Netherton, Stuart J; Ovens, Jeffrey D; Ferguson, Alastair V; Maurice, Donald H

    2007-03-01

    A very strong epidemiological link exists between obesity, the metabolic syndrome, diabetes and diabetes-associated cardiovascular pathologies. For this reason the peripheral effects of the centrally-acting satiety adipokines, adiponectin and leptin, and of non-adipose-derived hormones with similar effects, like ghrelin, have received considerable attention. In this report, we have extended our previous studies of the pro-thrombotic effects of leptin and determined the effects of adiponectin or ghrelin on human platelet activation. Thus, while leptin stimulated human platelet aggregation and adhesion, addition of adiponectin or of ghrelin did not affect either aggregation or adhesion of these cells; even at supra-physiological concentrations. In addition, we compared the impact of these three important hormones on microvascular endothelial cell permeability, an important parameter of endothelial function that when impaired contributes to several vascular pathologies. While physiologically relevant concentrations of either leptin or adiponectin increased the integrity of the diffusion barrier formed by a monolayer of human microvascular endothelial cells, only supra-physiological concentrations of ghrelin had this effect. None of these agents reduced microvascular endothelial barrier function. Taken together, our data are consistent with the ideas that leptin activates human platelets and limits transendothelial cell diffusion but that adiponectin only influences endothelial cell permeability. In contrast, ghrelin had neither of these effects. We propose that these data identify important differences in the effects of leptin, adiponectin or ghrelin on microvascular endothelial cells and platelets and may provide a basis on which to pharmacologically manipulate the selective effects of these peptides on these cell types in human cardiovascular or thrombotic diseases associated with obesity. PMID:17207790

  13. Adiponectin and leptin levels in HIV-infected subjects with insulin resistance and body fat redistribution.

    PubMed

    Mynarcik, Dennis C; Combs, Terry; McNurlan, Margaret A; Scherer, Philipp E; Komaroff, Eugene; Gelato, Marie C

    2002-12-15

    In this study, we sought to determine the relationship between serum levels of leptin and adiponectin (Acrp30) in patients with HIV-associated lipodystrophy (HIV-LD). Three groups of subjects were studied; HIV-positive subjects with lipodystrophy (HIV-LD; n = 22), HIV-positive subjects without lipodystrophy (HIV; n = 17), and ethnicity- and body mass index-matched healthy control subjects (n = 20). Although total body fat from dual energy x-ray absorptiometry was similar in all three groups, the HIV-LD group had a significantly lower mean proportion of body fat in the limbs +/- SEM (37.2% +/- 2.2%) than either controls (49.8% +/- 1.5%) or HIV subjects (45.7% +/- 2.0%). The HIV-LD group also had the lowest mean insulin sensitivity +/- SEM (5.11 +/- 0.59 mg of glucose/[kg of lean body mass. min] vs. 10.2 +/- 0.72 mg of glucose/[kg of lean body mass. min] in controls and 8.64 +/- 0.69 mg of glucose/[kg of lean body mass. min] in the HIV group). Leptin levels were similar in all three groups and were significantly correlated to total body fat (r = 0.86; p <.001), but these levels did not correlate with either insulin sensitivity or limb fat. Mean Acrp30 levels +/- SEM were lowest in the HIV-LD group (5.43 +/- 0.44 microg/mL vs. 11.2 +/- 1.4 microg/mL in the HIV group and 14.9 +/- 1.8 microg/mL in control subjects). Further, Acrp30 levels were positively correlated with insulin sensitivity (r = 0.610; p <.001) and limb fat (r = 0.483; p <.001). However, the correlation between limb fat and insulin sensitivity disappeared when Acrp30 level and other potential mediators were removed from the association, suggesting that a deficiency in Acrp30 in subjects with HIV-LD may be part of the mechanism for the reduced insulin sensitivity. PMID:12473840

  14. 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. PMID:25952883

  15. Running a Marathon Induces Changes in Adipokine Levels and in Markers of Cartilage Degradation – Novel Role for Resistin

    PubMed Central

    Vuolteenaho, Katriina; Leppänen, Tiina; Kekkonen, Riina; Korpela, Riitta; Moilanen, Eeva

    2014-01-01

    Running a marathon causes strenuous joint loading and increased energy expenditure. Adipokines regulate energy metabolism, but recent studies have indicated that they also exert a role in cartilage degradation in arthritis. Our aim was to investigate the effects of running a marathon on the levels of adipokines and indices of cartilage metabolism. Blood samples were obtained from 46 male marathoners before and after a marathon run. We measured levels of matrix metalloproteinase-3 (MMP-3), cartilage oligomeric protein (COMP) and chitinase 3-like protein 1 (YKL-40) as biomarkers of cartilage turnover and/or damage and plasma concentrations of adipokines adiponectin, leptin and resistin. Mean marathon time was 3∶30∶46±0∶02∶46 (h:min:sec). The exertion more than doubled MMP-3 levels and this change correlated negatively with the marathon time (r = –0.448, p = 0.002). YKL-40 levels increased by 56% and the effect on COMP release was variable. Running a marathon increased the levels of resistin and adiponectin, while leptin levels remained unchanged. The marathon-induced changes in resistin levels were positively associated with the changes in MMP-3 (r = 0.382, p = 0.009) and YKL-40 (r = 0.588, p<0.001) and the pre-marathon resistin levels correlated positively with the marathon induced change in YKL-40 (r = 0.386, p = 0.008). The present results show the impact of running a marathon, and possible load frequency, on cartilage metabolism: the faster the marathon was run, the greater was the increase in MMP-3 levels. Further, the results introduce pro-inflammatory adipocytokine resistin as a novel factor, which enhances during marathon race and associates with markers of cartilage degradation. PMID:25333960

  16. Leptin, Adiponectin and Cognition in Middle-aged HIV-infected and Uninfected Women. The Brooklyn Women’s Interagency HIV Study

    PubMed Central

    Gustafson, Deborah R; Mielke, Michelle M; Keating, Sheila A; Holman, Susan; Minkoff, Howard; Crystal, Howard A

    2016-01-01

    Context Case-control study of women with and without HIV infection. Objective To explore the association of cognition and the adipokines, leptin and adiponectin (total; high molecular weight, HMW), in women with (HIV+) and without HIV (HIV−) infection. Design Cross-sectional analyses of adipokines and cognition using linear regression models of log-transformed adipokines, and Trails A, Trails B, Stroop interference time, Stroop word recall, Stroop color naming and reading, and Symbol Digit Modalities Test (SDMT) with consideration for age, HIV infection status, education, CD4 count, diabetes, body mass index (BMI), waist circumference (WC) and race/ethnicity. Setting Brooklyn, NY. Participants 354 participants (247 HIV+, 107 HIV−), in the Brooklyn Women’s Interagency HIV Study (WIHS), average age 38.9 years, with measured levels of leptin and adiponectin (total and high molecular weight, HMW). Main Outcome Measure Cognition Results Higher levels of leptin were positively associated with worse cognition on the basis of Trails A completion time and SDMT score. Among at risk HIV− women, leptin was associated with worse performance on Trails B. No associations were observed for total or HMW adiponectin. Conclusion Blood adipokine levels were measured to provide mechanistic insights regarding the association of adipose with cognitive function. These data suggest that higher levels of leptin, consistent with more adipose tissue, are associated with worse cognitive function in middle age. Monitoring leptin over time and with increasing age in relation to cognition and dementia, may lend insights to the role of adipose tissue in successful body and brain aging among women with HIV infection. PMID:27536467

  17. Serum Concentrations of Insulin, Ghrelin, Adiponectin, Leptin, Leptin Receptor and Lipocalin-2 in Children with Celiac Disease Who Do and Do Not Adhere to a Gluten-Free Diet

    PubMed Central

    Janas, Roman M.; Rybak, Anna; Wierzbicka-Rucińska, Aldona; Socha, Piotr; Śnitko, Rafał; Szaflarska-Popławska, Anna; Stolarczyk, Anna; Oralewska, Beata; Cytra-Jarocka, Elżbieta; Iwańczak, Barbara; Grzybowska-Chlebowczyk, Urszula; Cichy, Wojciech; Czaja-Bulsa, Grażyna; Socha, Jerzy

    2016-01-01

    Background/Aims The roles of the many bioactive peptides in the pathogenesis of celiac disease remain unclear. To evaluate the serum concentrations of insulin, ghrelin, adiponectin, leptin, leptin receptor, and lipocalin-2 in children with celiac disease who do and do not adhere to a gluten-free diet (GFD, intermittent adherence). Methods Prepubertal, pubertal, and adolescent celiac children were included in this study (74 girls and 53 boys on a GFD and 80 girls and 40 boys off of a GFD). Results Insulin levels in prepubertal (9.01±4.43 μIU/mL), pubertal (10.3±3.62 μIU/mL), and adolescent (10.8±4.73 μIU/mL) girls were higher than those in boys (5.88±2.02, 8.81±2.88, and 8.81±2.26 μIU/mL, respectively) and were neither age-dependent nor influenced by a GFD. Prepubertal children off of a GFD exhibited higher ghrelin levels than prepubertal children on a GFD. Adiponectin levels were not age-, sex- nor GFD-dependent. Adherence to a GFD had no effect on the expression of leptin, leptin receptor, and lipocalin-2. Conclusions Adherence to a GFD had no influence on the adiponectin, leptin, leptin receptor, and lipocalin-2 concentrations in celiac children, but a GFD decreased highly elevated ghrelin levels in prepubertal children. Further studies are required to determine whether increased insulin concentrations in girls with celiac disease is suggestive of an increased risk for hyperinsulinemia. PMID:27074817

  18. Cardiomyocyte Antihypertrophic Effect of Adipose Tissue Conditioned Medium from Rats and Its Abrogation by Obesity is Mediated by the Leptin to Adiponectin Ratio

    PubMed Central

    Bairwa, Suresh C.; Rajapurohitam, Venkatesh; Gan, Xiaohong Tracey; Mangat, Rabban; Proctor, Spencer D.; Karmazyn, Morris

    2016-01-01

    White adipocytes are known to function as endocrine organs by secreting a plethora of bioactive adipokines which can regulate cardiac function including the development of hypertrophy. We determined whether adipose tissue conditioned medium (ATCM) generated from the epididymal regions of normal rats can affect the hypertrophic response of cultured rat ventricular myocytes to endothelin-1 (ET-1) administration. Myocytes were treated with ET-1 (10 nM) for 24 hours in the absence or presence of increasing ATCM concentrations. ATCM supressed the hypertrophic response to ET-1 in a concentration-dependent manner, an effect enhanced by the leptin receptor antagonist and attenuated by an antibody against the adiponectin AdipoR1 receptor. Antihypertrophic effects were also observed with ATCM generated from perirenal-derived adipose tissue. However, this effect was absent in ATCM from adipose tissue harvested from corpulent JCR:LA-cp rats. Detailed analyses of adipokine content in ATCM from normal and corpulent rats revealed no differences in the majority of products assayed, although a significant increase in leptin concentrations concomitant with decreased adiponectin levels was observed, resulting in a 11 fold increase in the leptin to adiponectin ratio in ATCM from JCR:LA-cp. The antihypertrophic effect of ATCM was associated with increased phosphorylation of AMP-activated protein kinase (AMPK), an effect abrogated by the AdipoR1 antibody. Moreover, the antihypertrophic effect of ATCM was mimicked by an AMPK activator. There was no effect of ET-1 on mitogen-activated protein kinase (MAPK) activities 24 hour after its addition either in the presence or absence of ATCM. Our study suggests that adipose tissue from healthy subjects exerts antihypertrophic effects via an adiponectin–dependent pathway which is impaired in obesity, most likely due to adipocyte remodelling resulting in enhanced leptin and reduced adiponectin levels. PMID:26731409

  19. The effects of paternal high-fat diet exposure on offspring metabolism with epigenetic changes in the mouse adiponectin and leptin gene promoters.

    PubMed

    Masuyama, Hisashi; Mitsui, Takashi; Eguchi, Takeshi; Tamada, Shoko; Hiramatsu, Yuji

    2016-07-01

    Recent studies have demonstrated that epigenetic changes resulting from malnutrition might play important roles in transgenerational links with metabolic diseases. Previously, we observed that exposure to a high-fat diet (HFD) in utero caused a metabolic syndrome-like phenomenon through epigenetic modifications of the adiponectin and leptin genes that persisted for multiple generations. Recent etiological studies indicated that paternal BMI had effects on offspring BMI that were independent of but additive to maternal BMI effects. Thus, we examined whether paternal HFD-induced obesity affected the metabolic status of offspring through epigenetic changes in the adiponectin and leptin genes. Additionally, we investigated whether a normal diet during subsequent generations abolished the epigenetic changes associated with paternal HFD exposure before conception. We observed the effects of paternal HFD exposure before conception over multiple generations on offspring metabolic traits, including weight and fat gain, glucose intolerance, hypertriglyceridemia, abnormal adipocytokine levels, hypertension, and adiponectin and leptin gene expression and epigenetic changes. Normal diet consumption by male offspring during the subsequent generation following paternal HFD exposure diminished whereas consumption for two generations completely abolished the effect of paternal HFD exposure on metabolic traits and adipocytokine promoter epigenetic changes in the offspring. The effects of paternal HFD exposure on offspring were relatively weaker than those following HFD exposure in utero. However, paternal HFD exposure had an additive metabolic effect for two generations, suggesting that both paternal and maternal nutrition might affect offspring metabolism through epigenetic modifications of adipocytokine genes for multiple generations. PMID:27245335

  20. Association of resistin with visceral fat and muscle insulin resistance.

    PubMed

    Borst, Stephen E; Conover, Christine F; Bagby, Gregory J

    2005-10-01

    Maturing Sprague-Dawley (S-D) rats develop obesity and skeletal muscle insulin resistance. To investigate the relationship between fat mass and insulin responses, we performed surgical removal of the epididymal and retroperitoneal depots of visceral adipose tissue (VF) or sham surgery (SHAM) in male rats aged 4 months. At sacrifice, 30 days later, the mass of visceral fat was 48% lower (p<0.05) in VF- compared to SHAM, while subcutaneous fat was essentially unchanged. VF- animals displayed increased insulin responses in isolated strips of skeletal muscle. Insulin-stimulated glucose transport was increased 28% in soleus muscle (p<0.05), with a trend toward a 31% increase in extensor digitorum longus muscle (p=0.058). Glucose tolerance was not significantly affected by surgical fat removal. In VF- animals, serum resistin was reduced 26% (p<0.05) and serum adiponectin was reduced 30% (p<0.05), with trends for reductions in IL-4 (58% reduction, p=0.084) and IL-6 (56% reduction, p=0.123). TNF-alpha, leptin and free fatty acids (NEFAs) were unchanged. We conclude that in maturing S-D rats, increased visceral adiposity leads to an increase in systemic release in resistin and possibly interleukins. Elevation of circulating cytokines may play a role in the development of muscle insulin resistance. PMID:16154759

  1. 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.

  2. Delivery Mode, Duration of Labor, and Cord Blood Adiponectin, Leptin, and C-Reactive Protein: Results of the Population-Based Ulm Birth Cohort Studies

    PubMed Central

    Logan, Chad A.; Thiel, Larissa; Bornemann, Rebecca; Koenig, Wolfgang; Reister, Frank; Brenner, Hermann; Rothenbacher, Dietrich; Genuneit, Jon

    2016-01-01

    Background Numerous studies have reported associations between delivery mode and health outcomes in infancy and later life. Previous smaller studies indicated a relationship between delivery mode and newborn inflammation potentially constituting a mediating factor. We aimed to determine the influence of delivery mode and duration of labor on cord blood concentrations of adiponectin, leptin, and high-sensitivity C-reactive protein (hs-CRP). Methods In the Ulm SPATZ Health Study, 934 singleton newborns and their mothers were recruited during their hospital stay in the University Medical Center Ulm, Southern Germany, from 04/2012-05/2013. Inflammatory biomarkers were measured by ELISAs (n = 836). Delivery mode was analyzed categorically (elective cesarean (reference), active labor delivery: emergency cesarean, assisted vaginal, and spontaneous vaginal); duration of labor continuously. Following log-transformation, linear regression was used to estimate geometric means ratios (GMR) adjusted for potential confounders for the effects of delivery mode and duration of labor on each biomarker separately. Independent replication was sought in the similarly conducted Ulm Birth Cohort Study recruited from 11/2000-11/2001. Results Individually, active labor delivery modes as well as increasing duration of labor were associated with higher leptin and hs-CRP concentrations. After mutual adjustment, the associations with delivery modes were attenuated but those for duration of labor remained statistically significant (GMR (95%CI) 1.10 (1.00; 1.21) and 1.15 (1.04; 1.27) for leptin and hs-CRP per hour of labor, respectively). No significant adjusted associations were observed between delivery modes and adiponectin concentrations. These findings were replicated in an independent birth cohort study. Conclusions Cord blood leptin and hs-CRP concentrations were associated with duration of labor rather than delivery mode. Further research is warranted to investigate these associations

  3. GnRH decreases adiponectin expression in pituitary gonadotropes via the calcium and PKA pathways.

    PubMed

    Kim, Jonathan; Zheng, Weiming; Grafer, Constance; Mann, Merry Lynn; Halvorson, Lisa M

    2013-08-01

    As endocrinologically active cells, adipocytes are capable of secreting various adipocytokines such as leptin, resistin, and adiponectin to impact metabolic function. Although adipocytes remain to be the primary site of synthesis and secretion, there is now growing evidence that supports the presence of adiponectin and its receptors within the hypothalamic-pituitary-gonadal axis, providing a possible link between obesity and abnormal reproductive physiology. It has been demonstrated that adiponectin may reduce gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus as well as modulate gonadal steroid hormone production. Furthermore, prior data indicate that adiponectin may play a role in decreasing luteinizing hormone secretion from pituitary gonadotropes. We aimed to identify the hormonal regulators of adiponectin and its receptors, AdipoR1 and AdipoR2, in pituitary gonadotropes using immortalized gonadotropic LβT2 cells and primary rat pituitary cells. Our study shows significant alterations in adiponectin expression across the estrous cycle. In addition, we present a novel finding that GnRH suppresses pituitary adiponectin expression via the calcium and protein kinase A intracellular pathways in both cultured rat primary pituitary cells and the LβT2 gonadotrope cell line. The GnRH did not alter expression of the adiponectin receptors, AdipoR1 and AdipoR2, in cultured gonadotropes. Expression of the adiponectin receptors, AdipoR1 and AdipoR2, was not altered by GnRH in cell culture but in vivo or in vitro. Our data suggest that gonadotrope function may be modulated by GnRH-mediated changes in adiponectin expression. PMID:23239819

  4. 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

  5. Endurance exercise alters cellular immune status and resistin concentrations in men suffering from non-insulin-dependent type 2 diabetes.

    PubMed

    Wenning, P; Kreutz, T; Schmidt, A; Opitz, D; Graf, C; Voss, S; Bloch, W; Brixius, K

    2013-08-01

    It has been demonstrated that alterations of adipocytokines can alter immune status in type 2 diabetes. The present study investigated changes of adipocytokine plasma concentrations and cellular immune status in overweight men, suffering from non-insulin dependent type 2 diabetes (n=14, age 61.0±8.7 years, BMI 31.1±3.5 kg/cm2). Subjects underwent a 3 months endurance exercise intervention (twice per week for up to 45 min) cycling at a heart rate corresponding to a 2 mmol/l lactate threshold. Before and after the intervention testing for adipocytokines (leptin, adiponectin, resistin) and cellular immune status (including T memory-cells and regulative T-cells) was performed by RIA and FACS accordingly.The exercise intervention improved anthropometric and metabolic parameters of all subjects. We observed a significant decline for resistin and for the CD19+ B-cells. The CD4+CD25+CD127low Treg-cells decreased, however not statistically significant. All other parameters remained unchanged.In conclusion, even though only training twice a week, the exercise affected parts of the cellular immune system as well as resistin levels in men suffering from non-insulin dependent type 2 diabetes. PMID:24026829

  6. Multi-Biomarkers for Early Detection of Type 2 Diabetes, Including 10- and 12-(Z,E)-Hydroxyoctadecadienoic Acids, Insulin, Leptin, and Adiponectin

    PubMed Central

    Umeno, Aya; Yoshino, Kohzoh; Hashimoto, Yoshiko; Shichiri, Mototada; Kataoka, Masatoshi; Yoshida, Yasukazu

    2015-01-01

    We have previously found that fasting plasma levels of totally assessed 10- and 12-(Z,E)-hydroxyoctadecadienoic acid (HODE) correlated well with levels of glycated hemoglobin (HbA1c) and glucose during oral glucose tolerance tests (OGTT); these levels were determined via liquid chromatography—mass spectrometry after reduction and saponification. However, 10- and 12-(Z,E)-HODE alone cannot perfectly detect early impaired glucose tolerance (IGT) and/or insulin resistance, which ultimately lead to diabetes. In this study, we randomly recruited healthy volunteers (n = 57) who had no known history of any diseases, and who were evaluated using the OGTT, the HODE biomarkers, and several additional proposed biomarkers, including retinol binding protein 4 (RBP4), adiponectin, leptin, insulin, glycoalbumin, and high sensitivity-C-reactive protein. The OGTT revealed that our volunteers included normal individuals (n = 44; Group N), “high-normal” individuals (fasting plasma glucose 100–109 mg/dL) with IGT (n = 11; Group HN+IGT), and diabetic individuals (n = 2; Group D). We then used these groups to evaluate the potential biomarkers for the early detection of type 2 diabetes. Plasma levels of RBP4 and glycoalbumin were higher in Group HN+IGT, compared to those in Group N, and fasting levels of 10- and 12-(Z,E)-HODE/linoleic acids were significantly correlated with levels of RBP4 (p = 0.003, r = 0.380) and glycoalbumin (p = 0.006, r = 0.316). Furthermore, we developed a stepwise multiple linear regression models to predict the individuals’ insulin resistance index (the Matsuda Index 3). Fasting plasma levels of 10- and 12-(Z,E)-HODE/linoleic acids, glucose, insulin, and leptin/adiponectin were selected as the explanatory variables for the models. The risks of type 2 diabetes, early IGT, and insulin resistance were perfectly predicted by comparing fasting glucose levels to the estimated Matsuda Index 3 (fasting levels of 10- and 12-(Z,E)-HODE/linoleic acids, insulin

  7. The Associations of Novel Vitamin D3 Metabolic Gene CYP27A1 Polymorphism, Adiponectin/Leptin Ratio, and Metabolic Syndrome in Middle-Aged Taiwanese Males

    PubMed Central

    Liu, Chia-Chu; Huang, Chun-Nung; Lee, Yung-Chin; Chu, Chih-Sheng; Chang, Chu-Fen; Kuo, Po-Lin; Lai, Wen-Ter

    2015-01-01

    Metabolic syndrome (MetS) confers increased risks of cardiovascular disease (CVD). Both vitamin D3 and adipocytokines (especially adiponectin and leptin) have a great impact on CVD and MetS. In vitamin D3 metabolism, the vitamin D3 25-hydroxylase (CYP27A1) and 25-hydroxyvitamin D3 1-alpha-hydroxylase (CYP27B1) are two key enzymes. This study aimed to examine the influence of vitamin D3 CYP27 single nucleotide polymorphisms (SNPs) on adipocytokines and MetS. Cross-sectional data and DNA samples were collected from male volunteers (n = 649, age: 55.7 ± 4.7 years). Two tagging SNPs, CYP27A1 rs4674344 and CYP27B1 rs10877012, were selected from the HapMap project. MetS was significantly associated with the CYP27A1 rs4674344 SNP (P = 0.04) and the ratio of adiponectin/leptin (A/L ratio) was most correlated to the CYP27A1 rs4674344 SNP, appearing to be significantly lower in T-carriers than in AA subjects (3.7 ± 4.0 versus 5.1 ± 6.0, P = 0.001) and significantly negatively associated after adjustment. For each MetS component associated with the CYP27A1 rs4674344 SNP, the A/L ratios were significantly negative in preclinical stage (condition not meeting the individual criteria), except the blood pressure. In conclusion, CYP27A1 rs4674344 SNP, A/L ratio, and MetS are significantly associated and T-carriers might have a higher risk of developing MetS due to low A/L ratios in the preclinical stage. PMID:25628655

  8. [The biological function of trophology, biological reactions of exo- and endotrophy the pathogenesis of metabolic syndrome, leptin and adiponectin: a lecture].

    PubMed

    Titov, V N

    2014-06-01

    The metabolic syndrome or overeating syndrome is a phylogenetically conditioned sequence of symptoms with common pathogenesis. The etiological factor of metabolic syndrome is higher consumption of food which is optimal on all other parameters. The enterocytes and adipocytes of omentum constitute in phylogenesis sense a unified cenosis regulated paracrinally and realizing by turns biological reactions of exo- and endotrophy. The visceral adiposity, higher level of unesterified fatty acids, formation of fatty acids pool in the form of micelle in blood, their embedding into endothelium membrane and increase of size of enterocytes are causes of increasing of hydro-dynamic pressure. The associates of albumin with more than physiologically needed amount of fatty acids are accepted by toll-similar receptors as "alien" and reaction of inflammation is initiated. In cells, overloaded with lipids "endoplasmatic stress" is developed, synthesis (folding) of proteins is disordered and their destruction similar to apoptosis is activated In a phylogenesis sense, the visceral fat is fatty acids 'depot to implement biological functions of homeostasis, trophology, endoecology and adaptation and which is regulated at the level of paracrin cenosis an is anatomically limited. The subcutaneous depot is a consequence of implementation of function of locomotion and has no limits in size. The visceral fatty cells have no receptors to philogenically late insulin. The specialized adipocytes with receptors to insulin and glucose transporter type 4 are the cells of subcutaneous depot of fatty acids. They are regulated philogenetically with late humoral mode at the level of organism. The leptin is an initiator of humoral hypothalamic regulation in vivo of size of visceral and insensible to insulin fatty acids qualitatively programmed in ontgogeny. Leptin prevents "endoplasmatic stress" and apoptosis of cells and regulates amount of consumed food Leptin initiates switching storage of fatty acids

  9. [Biological function of trophology and the pathogenesis of metabolic syndrome--syndrome of overeating. Phylogenetically theory of general pathology, role of leptin and adiponectin].

    PubMed

    Titov, V N

    2014-01-01

    Metabolic syndrome (overeating) is a phylogenetically-determined succession of symptoms with the same pathogenesis. There is only one etiological factor, namely, increased consumption of physiologically optimal food. Enterocytes and omental fat cells are a phylogenetically early paracrine-regulated cell community that realizes the biological reactions of exo- and endotrophy. Visceral obesity, high levels of unesterified fatty acids (FA), formation of a pool of micellar FA in the blood, integration of these FA into endothelial cell plasma membrane and enlargement of adipocytes are the causes of hydrodynamic pressure elevation. Toll-like receptors recognize the associates between albumin and greater than physiological number of FA as "foreing" and initiate inflammatory response. "Endoplasm stress" develops in lipid-overloaded cells, protein synthesis (folding) in them is impaired and apoptosis-like cell death is activated. Visceral fat is a phylogenetically early depot of FA to fulfill the biological function of homeostasis, trophology, endoecology and adaptation; it is regulated at the level of paracrine communities and is anatomically limited. The subcutaneous fat depot fulfills the phylogenetically late function of locomotion; the depot size is not anatomically limited. Visceral fat cells have no receptors for phylogenetically late insulin (INS); specialized adipocyes bearing INS and GLUT4 receptors are cells that form the subcutaneous depot. These cells are regulated by phylogenetically late humoral factors at the entire body level. Leptin is an initiator of humoral hypothalamic regulation of in vivo number of ontogenetically programmed number of visceral INS-insensitive fat cells. It prevents "endoplasm stress" and apoptosis, being designed to regulate the amount of consumed food. Leptin initiates storage of FA from visceral pool into subcutaneous pool. Adiponectin is a phylogenetically late humoral hypothalamic regulatory factor that controls optimal number of

  10. Fasting and postprandial regulation of the intracellular localization of adiponectin and of adipokines secretion by dietary fat in rats

    PubMed Central

    Olivares-García, V; Torre-Villalvazo, I; Velázquez-Villegas, L; Alemán, G; Lara, N; López-Romero, P; Torres, N; Tovar, A R; Díaz-Villaseñor, A

    2015-01-01

    Background/Objective: Dietary fat sources modulate fasting serum concentration of adipokines, particularly adiponectin. However, previous studies utilized obese animals in which adipose tissue function is severely altered. Thus, the present study aimed to assess the postprandial regulation of adipokine secretion in nonobese rats that consumed high-fat diet (HFD) composed of different types of fat for a short time. Methods: The rats were fed a control diet or a HFD containing coconut, safflower or soybean oil (rich in saturated fatty acid, monounsaturated fatty acid or polyunsaturated fatty acid, respectively) for 21 days. The serum concentrations of adiponectin, leptin, retinol, retinol-binding protein-4 (RBP-4), visfatin and resistin were determined at fasting and after refeeding. Adiponectin multimerization and intracellular localization, as well as the expression of endoplasmic reticulum (ER) chaperones and transcriptional regulators, were evaluated in epididymal white adipose tissue. Results: In HFD-fed rats, serum adiponectin was significantly decreased 30 min after refeeding. With coconut oil, all three multimeric forms were reduced; with safflower oil, only the high-molecular-weight (HMW) and medium-molecular-weight (MMW) forms were decreased; and with soybean oil, only the HMW form was diminished. These reductions were due not to modifications in mRNA abundance or adiponectin multimerization but rather to an increment in intracellular localization at the ER and plasma membrane. Thus, when rats consumed a HFD, the type of dietary fat differentially affected the abundance of endoplasmic reticulum resident protein 44 kDa (ERp44), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ (PPARγ) mRNAs, all of which are involved in the post-translational processing of adiponectin required for its secretion. Leptin, RBP-4, resistin and visfatin serum concentrations did not change during fasting, whereas modest alterations were observed after

  11. 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

  12. 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

    2015-01-01

    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. PMID:26667726

  13. Osteoarthritis: genes, nature-nurture interaction and the role of leptin.

    PubMed

    Garner, Malgorzata; Alshameeri, Zeiad; Khanduja, Vikas

    2013-12-01

    Osteoarthritis (OA) is a common disease affecting patients at different ages regardless of gender or ethnicity. As with many chronic diseases, OA is thought to have a multifactorial aetiology, which is not fully understood. Whereas the pathophysiological process of OA can be analysed at a cellular and molecular level, the interaction between genes and lifestyle remains an important factor in the development of this disease. The expanding awareness of different genes that may play a role in OA, together with many chemical mediators thought to be associated with the progression of the disease, will help in better management of this condition. Some of the chemical mediators recently implicated in this condition are the adipokines (leptin, adiponectin and resistin). Few but consistent studies suggest that leptin in association with obesity could be an important factor in OA aetiology. Hence, this could establish a strong and direct molecular link between patient life style (nurture) and the pathological process of OA (nature). However, neither a clear mechanism nor a direct clinical association linking leptin to OA has yet been established. In this article, we explore some of the genetic and environmental factors in OA aetiology. We discuss leptin in obesity and assess its possible association with OA aetiology. This should emphasise the important role of health professionals in treating obesity in order to control OA symptoms and possibly progression. PMID:24036528

  14. Leptin Is Associated With Persistence of Hyperglycemia in Acute Pancreatitis

    PubMed Central

    Kennedy, James I.C.; Askelund, Kathryn J.; Premkumar, Rakesh; Phillips, Anthony R.J.; Murphy, Rinki; Windsor, John A.; Petrov, Maxim S.

    2016-01-01

    Abstract Adipokines have many homeostatic roles, including modulation of glucose metabolism, but their role in the pathophysiology of hyperglycemia associated with acute and critical illnesses in general, and acute pancreatitis (AP) in particular, is largely unknown. This study aimed to investigate the relationship between a panel of adipokines and hyperglycemia in the early course of AP, as well as the role of adipokines as predictors of AP severity. Adiponectin, leptin, omentin, resistin, and visfatin were measured on a daily basis in the first 72 hours after hospital admission. A first set of analyses was undertaken with admission glycemia stratified by severity, and a second set of analyses was undertaken based on persistence of early hyperglycemia. All of the analyses were adjusted for confounders. A total of 32 patients with AP were included in this study. None of the studied adipokines was significantly associated with glucose level on admission. Leptin was significantly (P = 0.003) increased in patients with persistent hyperglycemia. Adiponectin was significantly associated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in patients with persistent hyperglycemia (P = 0.015), visfatin with APACHE II score in patients with persistent hyperglycemia (P = 0.014), and omentin with APACHE II score in all of the patients regardless of the presence or absence of hyperglycemia (P = 0.021). Leptin is significantly associated with persistent hyperglycemia in the early course of AP. Omentin has a potential to become an accurate predictor of AP severity. PMID:26871770

  15. Resistin as an Intrahepatic Cytokine

    PubMed Central

    Bertolani, Cristiana; Sancho-Bru, Pau; Failli, Paola; Bataller, Ramon; Aleffi, Sara; DeFranco, Raffaella; Mazzinghi, Benedetta; Romagnani, Paola; Milani, Stefano; Ginés, Pere; Colmenero, Jordi; Parola, Maurizio; Gelmini, Stefania; Tarquini, Roberto; Laffi, Giacomo; Pinzani, Massimo; Marra, Fabio

    2006-01-01

    Obesity and insulin resistance accelerate the progression of fibrosis during chronic liver disease. Resistin antagonizes insulin action in rodents, but its role in humans is still controversial. The aims of this study were to investigate resistin expression in human liver and to evaluate whether resistin may affect the biology of activated human hepatic stellate cells (HSCs), key modulators of hepatic fibrogenesis. Resistin gene expression was low in normal human liver but was increased in conditions of severe fibrosis. Up-regulation of resistin during chronic liver damage was confirmed by immunohistochemistry. In a group of patients with alcoholic hepatitis, resistin expression correlated with inflammation and fibrosis, suggesting a possible action on HSCs. Exposure of cultured HSCs to recombinant resistin resulted in increased expression of the proinflammatory chemokines monocyte chemoattractant protein-1 and interleukin-8, through activation of nuclear factor (NF)-κB. Resistin induced a rapid increase in intracellular calcium concentration, mainly through calcium release from intracellular inositol triphosphate-sensitive pools. The intracellular calcium chelator BAPTA-AM blocked resistin-induced NF-κB activation and monocyte chemoattractant protein-1 expression. In conclusion, this study shows a role for resistin as an intrahepatic cytokine exerting proinflammatory actions in HSCs, via a Ca2+/NF-κB-dependent pathway and suggests involvement of this adipokine in the pathophysiology of liver fibrosis. PMID:17148667

  16. Resistin in idiopathic inflammatory myopathies

    PubMed Central

    2012-01-01

    Introduction The purpose of this study was to evaluate and compare the serum levels and local expression of resistin in patients with idiopathic inflammatory myopathies to controls, and to determine the relationship between resistin levels, inflammation and disease activity. Methods Serum resistin levels were determined in 42 patients with inflammatory myopathies and 27 healthy controls. The association among resistin levels, inflammation, global disease activity and muscle strength was examined. The expression of resistin in muscle tissues from patients with inflammatory myopathies and healthy controls was evaluated. Gene expression and protein release from resistin-stimulated muscle and mononuclear cells were assessed. Results In patients with inflammatory myopathies, the serum levels of resistin were significantly higher than those observed in controls (8.53 ± 6.84 vs. 4.54 ± 1.08 ng/ml, P < 0.0001) and correlated with C-reactive protein (CRP) levels (r = 0.328, P = 0.044) and myositis disease activity assessment visual analogue scales (MYOACT) (r = 0.382, P = 0.026). Stronger association was observed between the levels of serum resistin and CRP levels (r = 0.717, P = 0.037) as well as MYOACT (r = 0.798, P = 0.007), and there was a trend towards correlation between serum resistin and myoglobin levels (r = 0.650, P = 0.067) in anti-Jo-1 positive patients. Furthermore, in patients with dermatomyositis, serum resistin levels significantly correlated with MYOACT (r = 0.667, P = 0.001), creatine kinase (r = 0.739, P = 0.001) and myoglobin levels (r = 0.791, P = 0.0003) and showed a trend towards correlation with CRP levels (r = 0.447, P = 0.067). Resistin expression in muscle tissue was significantly higher in patients with inflammatory myopathies compared to controls, and resistin induced the expression of interleukins (IL)-1β and IL-6 and monocyte chemoattractant protein (MCP)-1 in mononuclear cells but not in myocytes. Conclusions The results of this study

  17. 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

  18. Cloning and characterization of porcine resistin gene.

    PubMed

    Dai, M H; Xia, T; Chen, X D; Gan, L; Feng, S Q; Qiu, H; Peng, Y; Yang, Z Q

    2006-02-01

    Resistin is a member of resistin-like molecules (RELMs) and a hormone secreted from mature adipocytes in rodents and leukocytes in human. We now report the cloning and characterization of the full-length porcine resistin cDNA and gene. Sequence analysis indicated that the pig resistin cDNA sequence had an open reading frame of 330 bp encoding a 12 kDa protein of 109 amino acids. The deduced amino acid sequence showed 75.2% identity to the human resistin. The porcine resistin gene was composed of four exons and had exactly the same exon structure as the human resistin gene. The tissue distribution of porcine resistin mRNA was assessed by semi-quantitative RT-PCR. Resistin gene expression was the highest in porcine leukocytes and low in adipose tissue. Resistin protein could be detected in porcine serum by western blotting and it circulated in serum as dimers and trimers. We provided the first evidence that resistin was abundantly expressed in porcine leukocytes and had an expression pattern similar to that in human resistin mRNA and protein. This suggests that the pig may be a suitable animal model for studying the function of resistin in human insulin resistance. PMID:16023825

  19. Association of Adiponectin Gene Polymorphism with Adiponectin Levels And Risk for Insulin Resistance Syndrome

    PubMed Central

    Prakash, Jai; Mittal, Balraj; Awasthi, Shally; Srivastava, Neena

    2015-01-01

    Background: Adiponectin is an abundant adipose tissue–derived protein with anti-atherogenic, anti-inflammatory and antidiabetic properties. Plasma adiponectin levels are decreased in obesity, type 2 diabetes, and coronary artery disease and low adiponectin levels also predict insulin resistance (IR). Methods: Case-control study in which 642 male and female subjects were participated from the North Indian population. Lipid, insulin, leptin and adiponectin level were estimated using standard protocols by commercially available test kits. Single nucleotide polymorphisms +45T>G and +276G>T of the AMP1 (adiponectin) gene was genotyped by polymerase chain reaction restriction fragment length polymorphism method. Results: Levels of adiponectin, insulin, homeostasis model assessment-IR index (HOMA-IR index), systolic blood pressure and fat mass showed significant differences between male and female subjects. Serum adiponectin level showed highly significant association with both the +45 and the +276 genotypes. The common haplotype triglyceride (TG) showed a significantly lower adiponectin value than other haplotypes (P = 0.0001). A clear trend of decreasing adiponectin levels per copy of the common haplotype was observed. Nonobese insulin sensitive subjects showed a higher adiponectin value (P = 0.0006) than nonobese insulin resistant subjects. The values of blood pressure, adiponectin, insulin, HOMA-IR, total-cholesterol, and low-density lipoprotein-cholesterol significantly associated with TG haplotype. Conclusions: We observed the very strong association of the adiponectin 45-276 genotypes and haplotypes with adiponectin levels in healthy north Indian population and TG haplotypes also associated with metabolic parameters of the IR syndrome. PMID:25949781

  20. Central adiponectin acutely improves glucose tolerance in male mice.

    PubMed

    Koch, Christiane E; Lowe, Chrishanthi; Legler, Karen; Benzler, Jonas; Boucsein, Alisa; Böttiger, Gregor; Grattan, David R; Williams, Lynda M; Tups, Alexander

    2014-05-01

    Adiponectin, an adipocyte-derived hormone, regulates glucose and lipid metabolism. It is also antiinflammatory. During obesity, adiponectin levels and sensitivity are reduced. Whereas the action of adiponectin in the periphery is well established the neuroendocrine role of adiponectin is largely unknown. To address this we analyzed the expression of adiponectin and the 2 adiponectin receptors (AdipoR1 and AdipoR2) in response to fasting and to diet-induced and genetic obesity. We also investigated the acute impact of adiponectin on central regulation of glucose homeostasis. Adiponectin (1 μg) was injected intracerebroventricularly (ICV), and glucose tolerance tests were performed in dietary and genetic obese mice. Finally, the influence of ICV adiponectin administration on central signaling cascades regulating glucose homeostasis and on markers of hypothalamic inflammation was assessed. Gene expression of adiponectin was down-regulated whereas AdipoR1 was up-regulated in the arcuate nucleus of fasted mice. High-fat (HF) feeding increased AdipoR1 and AdipoR2 gene expression in this region. In mice on a HF diet and in leptin-deficient mice acute ICV adiponectin improved glucose tolerance 60 minutes after injection, whereas normoglycemia in control mice was unaffected. ICV adiponectin increased pAKT, decreased phospho-AMP-activated protein kinase, and did not change phospho-signal transducer and activator of transcription 3 immunoreactivity. In HF-fed mice, ICV adiponectin reversed parameters of hypothalamic inflammation and insulin resistance as determined by the number of phospho-glycogen synthase kinase 3 β(Ser9) and phospho-c-Jun N-terminal kinase (Thr183/Tyr185) immunoreactive cells in the arcuate nucleus and ventromedial hypothalamus. This study demonstrates that the insulin-sensitizing properties of adiponectin are at least partially based on a neuroendocrine mechanism that involves centrally synthesized adiponectin. PMID:24564394

  1. Adiponectin and leptin: new targets in inflammation.

    PubMed

    Scotece, Morena; Conde, Javier; López, Verónica; Lago, Francisca; Pino, Jesús; Gómez-Reino, Juan Jesús; Gualillo, Oreste

    2014-01-01

    Inflammation is a complex mechanism of cell/tissue responses to injuries triggered by multiple causes, including trauma, pathogens or autoimmune abnormal responses. In the last years, a novel line of thought is emerging by giving a more holistic vision of chronic arthropathies through a recently identified group of molecules, called adipokines. Actually, most of these recently identified factors, produced prevalently by white adipose tissue but also by cells of the joints (chondrocytes and synovial fibroblasts) and immune cells, play a significant role in chronic inflammation. Adipokines dysregulation has emerged as a common characteristic of chronic inflammation in rheumatic diseases in particular when obesity or, more precisely, adipose tissue dysfunction is associated with common rheumatic diseases, such as osteoarthritis and rheumatoid arthritis. In this MiniReview, we discuss the role of adipokines in osteoarthritis and rheumatoid arthritis providing an updated overview of their pathophysiological role and potential use as therapeutic targets. PMID:23834523

  2. Evolution of the Vertebrate Resistin Gene Family

    PubMed Central

    Hu, Qingda; Tan, Huanran; Irwin, David M.

    2015-01-01

    Resistin (encoded by Retn) was previously identified in rodents as a hormone associated with diabetes; however human resistin is instead linked to inflammation. Resistin is a member of a small gene family that includes the resistin-like peptides (encoded by Retnl genes) in mammals. Genomic searches of available genome sequences of diverse vertebrates and phylogenetic analyses were conducted to determine the size and origin of the resistin-like gene family. Genes encoding peptides similar to resistin were found in Mammalia, Sauria, Amphibia, and Actinistia (coelacanth, a lobe-finned fish), but not in Aves or fish from Actinopterygii, Chondrichthyes, or Agnatha. Retnl originated by duplication and transposition from Retn on the early mammalian lineage after divergence of the platypus, but before the placental and marsupial mammal divergence. The resistin-like gene family illustrates an instance where the locus of origin of duplicated genes can be identified, with Retn continuing to reside at this location. Mammalian species typically have a single copy Retn gene, but are much more variable in their numbers of Retnl genes, ranging from 0 to 9. Since Retn is located at the locus of origin, thus likely retained the ancestral expression pattern, largely maintained its copy number, and did not display accelerated evolution, we suggest that it is more likely to have maintained an ancestral function, while Retnl, which transposed to a new location, displays accelerated evolution, and shows greater variability in gene number, including gene loss, likely evolved new, but potentially lineage-specific, functions. PMID:26076481

  3. Evolution of the Vertebrate Resistin Gene Family.

    PubMed

    Hu, Qingda; Tan, Huanran; Irwin, David M

    2015-01-01

    Resistin (encoded by Retn) was previously identified in rodents as a hormone associated with diabetes; however human resistin is instead linked to inflammation. Resistin is a member of a small gene family that includes the resistin-like peptides (encoded by Retnl genes) in mammals. Genomic searches of available genome sequences of diverse vertebrates and phylogenetic analyses were conducted to determine the size and origin of the resistin-like gene family. Genes encoding peptides similar to resistin were found in Mammalia, Sauria, Amphibia, and Actinistia (coelacanth, a lobe-finned fish), but not in Aves or fish from Actinopterygii, Chondrichthyes, or Agnatha. Retnl originated by duplication and transposition from Retn on the early mammalian lineage after divergence of the platypus, but before the placental and marsupial mammal divergence. The resistin-like gene family illustrates an instance where the locus of origin of duplicated genes can be identified, with Retn continuing to reside at this location. Mammalian species typically have a single copy Retn gene, but are much more variable in their numbers of Retnl genes, ranging from 0 to 9. Since Retn is located at the locus of origin, thus likely retained the ancestral expression pattern, largely maintained its copy number, and did not display accelerated evolution, we suggest that it is more likely to have maintained an ancestral function, while Retnl, which transposed to a new location, displays accelerated evolution, and shows greater variability in gene number, including gene loss, likely evolved new, but potentially lineage-specific, functions. PMID:26076481

  4. Relationship of adiponectin and its multimers to metabolic indices in cats during weight change.

    PubMed

    Witzel, A L; Kirk, C A; Kania, S A; Bartges, J W; Boston, R C; Moyers, T; Byrd, H; Lauten, S

    2015-10-01

    Adiponectin is an important anti-inflammatory hormone secreted from adipose tissue. The high-molecular-weight form of adiponectin (HMW) closely correlates with insulin sensitivity in human beings. This study uses a novel method of size-exclusion gel chromatography combined with enzyme-linked immunosorbent assay to measure HMW feline adiponectin and determine its relationship to leptin, cholesterol, and insulin sensitivity as cats gain and lose weight. In addition, total adiponectin and its messenger RNA expression in subcutaneous adipose tissue were measured. No correlations were found between total serum adiponectin and subcutaneous adipose messenger RNA expression, fat mass, or measures of insulin sensitivity. This study demonstrates that cats have high percentages of HMW adiponectin. Although weak correlations between HMW adiponectin and fat mass were detected, additional cats are needed to determine if the correlations are significant. PMID:26143302

  5. Conventional kinesin KIF5B mediates adiponectin secretion in 3T3-L1 adipocytes.

    PubMed

    Cui, Ju; Pang, Jing; Lin, Ya-Jun; Jiang, Ping; Gong, Huan; Wang, Zai; Li, Jian; Cai, Jian-Ping; Huang, Jian-Dong; Zhang, Tie-Mei

    2016-08-01

    Insulin stimulates adiponectin secretion and glucose transporter type 4 (GLUT4) translocation in adipocyte to regulate metabolism homeostasis. Similar to GLUT4 translocation, intracellular trafficking and release of adiponectin in adipocytes relies on the trans-Golgi network and endosomal system. Recent studies show that the heavy chain of conventional kinesin (KIF5B) mediates GLUT4 translocation in murine 3T3-L1 adipocytes, however, the motor machinery involved in mediating intracellular trafficking and release of adiponectin is unknown. Here, we examined the role of KIF5B in the regulation of adiponectin secretion. The KIF5B level was up-regulated during 3T3-L1 adipogenesis. This increase in cytosolic KIF5B was synchronized with the induction of adiponectin. Endogenous KIF5B and adiponectin were partially colocalized at the peri-nuclear and cytosolic regions. In addition, adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. Knockdown of KIF5B resulted in a marked inhibition of adiponectin secretion and overexpression of KIF5B enhanced adiponectin release, whereas leptin secretion was not affected by changes in KIF5B expression. These data suggest that the secretion of adiponectin, but not leptin, is dependent on functional KIF5B. PMID:27264953

  6. Polymorphisms of the resistin gene and their association with obesity and resistin levels in Malaysian Malays.

    PubMed

    Apalasamy, Yamunah Devi; Rampal, Sanjay; Salim, Agus; Moy, Foong Ming; Su, Tin Tin; Majid, Hazreen Abdul; Bulgiba, Awang; Mohamed, Zahurin

    2015-06-01

    Single nucleotide polymorphisms (SNP) in the resistin gene (RETN) are linked to obesity and resistin levels in various populations. However, results have been inconsistent. This study aimed to investigate association between polymorphisms in the resistin gene with obesity in a homogenous Malaysian Malay population. This study is also aimed to determine association between resistin levels with certain SNPs and haplotypes of RETN. A total of 631 Malaysian Malay subjects were included in this study and genotyping was carried out using Sequenom MassARRAY. There was no significant difference found in both allelic and genotype frequencies of each of the RETN SNPs between the obese and non-obese groups after Bonferroni correction. RETN rs34861192 and rs3219175 SNPs were significantly associated with log-resistin levels. The GG genotype carriers are found to have higher levels of log-resistin compared to A allele carriers. The RETN haplotypes (CAG, CGA and GA) were significantly associated with resistin levels. However, the haplotypes of the RETN gene were not associated with obesity. Resistin levels were not correlated to metabolic parameters such as body weight, waist circumference, body mass index, and lipid parameters. RETN SNPs and haplotypes are of apparent functional importance in the regulation of resistin levels but are not correlated with obesity and related markers. PMID:25991560

  7. Long-time alcohol intake modifies resistin secretion and expression of resistin gene in adipose tissue.

    PubMed

    Pravdová, E; Macho, L; Hlavácová, N; Ficková, M

    2007-09-01

    Elevated serum resistin is implicated in insulin resistance associated with obesity and type 2 diabetes mellitus. Alcohol consumption interferes with the nutritional status, metabolic and hormonal activity of the drinker. Impact of ethanol intake on resistin level and resistin metabolic effects is unknown. Effect of long-time (28 days) ad libitum moderate alcohol (6% ethanol solution) intake on serum resistin and resistin mRNA level in adipose tissue of rats (A) was compared to control (C) and pair-fed (PF) animals. PF rats were fed the same caloric amount as A rats on previous day. Alcohol consumption resulted in reduction of food and energy intake, decreased body mass gain, epididymal fat pads mass and smaller adipocytes (vs. C rats). Alcohol intake significantly increased serum resistin and glucose, insulinemia remained unchanged. Systemic insulin resistance was not proved by HOMA, QUICKI and McAuley indexes, but impaired insulin effect on glucose transport in isolated adipocytes was present. Elevated serum resistin was positively correlated with glycemia (r = 0.88, p < 0.01) and negatively with fat cell size (r = -0.73, p < 0.05). High resistin level as the consequence of long-time alcohol intake could contribute to smaller adipocytes, higher glycemia, attenuation of insulin-stimulated glucose transport in adipocytes. Diminished resistin gene expression in adipose tissue of A and PF rats was present. PMID:18063850

  8. Adiponectin in childhood.

    PubMed

    Jeffery, Alison N; Murphy, Michael J; Metcalf, Brad S; Hosking, Joanne; Voss, Linda D; English, Patrick; Sattar, Naveed; Wilkin, Terence J

    2008-01-01

    Adiponectin, a hormone produced and secreted by adipocytes, is present in circulation in high circulating concentrations, suggesting an important physiological role. An indirect regulator of glucose metabolism, adiponectin increases insulin sensitivity, improves glucose tolerance and inhibits inflammation. Plasma adiponectin relates inversely to adiposity and, importantly, reflects the sequelae of accumulation of excess adiposity. The role of adiponectin in adults has been explored in detail. Studies in children are now available and, given the increasing rates of childhood obesity, it is important to establish the role of adiponectin in mediating insulin resistance and cardiovascular disease in this age group. This paper reviews the regulation of adiponectin, its effect on body mass, glucose metabolism and cardiovascular risk in infants, children and adolescents. It demonstrates clear links between adiponectin and features of the metabolic syndrome in obese children and adolescents. However, adiponectin's role as a predictor of metabolic dysfunction in healthy, normal-weight youngsters is less clear. PMID:19086185

  9. Resistin increases monolayer permeability of human coronary artery endothelial cells.

    PubMed

    Jamaluddin, Md Saha; Yan, Shaoyu; Lü, Jianming; Liang, Zhengdong; Yao, Qizhi; Chen, Changyi

    2013-01-01

    Resistin has been linked to obesity, insulin resistance, atherosclerosis, and the development of cardiovascular disease. Nevertheless, the effects and the molecular mechanisms of resistin on endothelial permeability, a key event in the development of atherosclerosis, inflammation, and vascular disease, are largely unknown. In order to determine the effect of resistin on endothelial permeability, human coronary artery endothelial cells (HCAECs) were treated with clinically relevant concentrations of resistin and the endothelial permeability was measured using the Transwell system with a Texas-Red-labeled dextran tracer. The permeability of HCAEC monolayers treated with resistin (80 ng/mL) was 51% higher than the permeability of control monolayers (P<0.05). The mRNA levels of tight junction proteins zonula occludens-1 (ZO-1) and occludin in resistin-treated cells were 37% and 42% lower, respectively, than the corresponding levels in untreated cells. The protein levels of these molecules in resistin-treated cells were significantly reduced by 35% and 37%, respectively (P<0.05), as shown by flow cytometry and Western blot analysis. Superoxide dismutase (SOD) mimetic MnTBAP effectively blocked the resistin-mediated reduction of ZO-1 and occludin levels in HCAECs. In addition, superoxide anion production was increased from 21% (untreated cells) to 55% (cells treated with 40 ng/mL resistin), and 64% (resistin, 80 mg/mL) (P<0.05). The natural antioxidant Ginkgolide A effectively inhibited resistin-induced increase in permeability and the increase in superoxide anion production in HCAECs. Furthermore, resistin treatment significantly activated p38 MAPK, but not ERK1/2. Pretreatment of HCAECs with a p38 inhibitor effectively blocked resistin-induced permeability. These results provide new evidence that resistin may contribute to the vascular lesion formation via increasing endothelial permeability through the mechanism of oxidative stress and the activation of p38 MAPK. PMID

  10. Resistin Increases Monolayer Permeability of Human Coronary Artery Endothelial Cells

    PubMed Central

    Jamaluddin, Md Saha; Yan, Shaoyu; Lü, Jianming; Liang, Zhengdong; Yao, Qizhi; Chen, Changyi

    2013-01-01

    Resistin has been linked to obesity, insulin resistance, atherosclerosis, and the development of cardiovascular disease. Nevertheless, the effects and the molecular mechanisms of resistin on endothelial permeability, a key event in the development of atherosclerosis, inflammation, and vascular disease, are largely unknown. In order to determine the effect of resistin on endothelial permeability, human coronary artery endothelial cells (HCAECs) were treated with clinically relevant concentrations of resistin and the endothelial permeability was measured using the Transwell system with a Texas-Red-labeled dextran tracer. The permeability of HCAEC monolayers treated with resistin (80 ng/mL) was 51% higher than the permeability of control monolayers (P<0.05). The mRNA levels of tight junction proteins zonula occludens-1 (ZO-1) and occludin in resistin-treated cells were 37% and 42% lower, respectively, than the corresponding levels in untreated cells. The protein levels of these molecules in resistin-treated cells were significantly reduced by 35% and 37%, respectively (P<0.05), as shown by flow cytometry and Western blot analysis. Superoxide dismutase (SOD) mimetic MnTBAP effectively blocked the resistin-mediated reduction of ZO-1 and occludin levels in HCAECs. In addition, superoxide anion production was increased from 21% (untreated cells) to 55% (cells treated with 40 ng/mL resistin), and 64% (resistin, 80 mg/mL) (P<0.05). The natural antioxidant Ginkgolide A effectively inhibited resistin-induced increase in permeability and the increase in superoxide anion production in HCAECs. Furthermore, resistin treatment significantly activated p38 MAPK, but not ERK1/2. Pretreatment of HCAECs with a p38 inhibitor effectively blocked resistin-induced permeability. These results provide new evidence that resistin may contribute to the vascular lesion formation via increasing endothelial permeability through the mechanism of oxidative stress and the activation of p38 MAPK. PMID

  11. Endothelin-1 stimulates resistin gene expression.

    PubMed

    Tang, Ya-Chu; Liu, Chi-Wei; Chang, Hsin-Huei; Juan, Chi-Chang; Kuo, Yow-Chii; Kao, Chung-Cheng; Huang, Yao-Ming; Kao, Yung-Hsi

    2014-03-01

    Resistin and endothelin (ET)-1 have been reported to inhibit adipogenesis and regulate adipocyte insulin resistance, respectively. Although both hormones interact with each other, the exact signaling pathway of ET-1 to act on resistin gene expression is still unknown. Using 3T3-L1 adipocytes, we investigated the signaling pathways involved in ET-1-stimulated resistin gene expression. The up-regulation of resistin mRNA expression by ET-1 depends on concentration and timing. The concentration of ET-1 that increased resistin mRNA levels by 100%-250% was approximately 100 nM for a range of 0.25-12 hours of treatment. Treatment with actinomycin D blocked ET-1-increased resistin mRNA levels, suggesting that the effect of ET-1 requires new mRNA synthesis. Treatment with an inhibitor of the ET type-A receptor, such as N-[1-Formyl-N-[N-[(hexahydro-1H-azepin-1-yl)carbonyl]-L-leucyl]-D-tryptophyl]-D-tryptophan (BQ610), but not with the ET type-B receptor antagonist N-[(cis-2,6-Dimethyl-1-piperidinyl)carbonyl]-4-methyl-L-leucyl-1-(methoxycarbonyl)-D-tryptophyl-D-norleucine (BQ788), blocked ET-1, increased the levels of resistin mRNA, and phosphorylated levels of downstream signaling molecules, such as ERK1/2, c-Jun N-terminal kinases (JNKs), protein kinase B (AKT), and signal transducer and activator of transcription 3 (STAT3). Moreover, pretreatment of specific inhibitors of either ERK1/2 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene [U0126] and 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one [PD98059], two inhibitors of MEK1), JNKs (SP600125), phosphatidylinositol 3-kinase/AKT (LY294002 and Wortmannin), or Janus kinase 2 (JAK2)/STAT3 ((E)-2-Cyano-3-(3,4-dihydrophenyl)-N-(phenylmethyl)-2-propenamide, AG490) prevented ET-1-increased levels of resistin mRNA and reduced the ET-1-stimulated phosphorylation of ERK1/2, JNKs, AKT, and STAT3, respectively. However, the p38 kinase antagonist 4-[5-(4-Fluorophenyl)-2-[4-(methylsulfonyl)phenyl]-1H-imidazol-4-yl

  12. Urinary Adiponectin Excretion

    PubMed Central

    von Eynatten, Maximilian; Liu, Dan; Hock, Cornelia; Oikonomou, Dimitrios; Baumann, Marcus; Allolio, Bruno; Korosoglou, Grigorios; Morcos, Michael; Campean, Valentina; Amann, Kerstin; Lutz, Jens; Heemann, Uwe; Nawroth, Peter P.; Bierhaus, Angelika; Humpert, Per M.

    2009-01-01

    OBJECTIVE Markers reliably identifying vascular damage and risk in diabetic patients are rare, and reports on associations of serum adiponectin with macrovascular disease have been inconsistent. In contrast to existing data on serum adiponectin, this study assesses whether urinary adiponectin excretion might represent a more consistent vascular damage marker in type 2 diabetes. RESEARCH DESIGN AND METHODS Adiponectin distribution in human kidney biopsies was assessed by immunohistochemistry, and urinary adiponectin isoforms were characterized by Western blot analysis. Total urinary adiponectin excretion rate was measured in 156 patients with type 2 diabetes who had a history of diabetic nephropathy and 40 healthy control subjects using enzyme-linked immunosorbent assay. Atherosclerotic burden was assessed by common carotid artery intima-media-thickness (IMT). RESULTS A homogenous staining of adiponectin was found on the endothelial surface of glomerular capillaries and intrarenal arterioles in nondiabetic kidneys, whereas staining was decreased in diabetic nephropathy. Low-molecular adiponectin isoforms (∼30–70 kDa) were detected in urine by Western blot analysis. Urinary adiponectin was significantly increased in type 2 diabetes (7.68 ± 14.26 vs. control subjects: 2.91 ± 3.85 μg/g creatinine, P = 0.008). Among type 2 diabetic patients, adiponectinuria was associated with IMT (r = 0.479, P < 0.001) and proved to be a powerful independent predictor of IMT (β = 0.360, P < 0.001) in multivariable regression analyses. In a risk prediction model including variables of the UK Prospective Diabetes Study coronary heart disease risk engine urinary adiponectin, but not the albumin excretion rate, added significant value for the prediction of increased IMT (P = 0.007). CONCLUSIONS Quantification of urinary adiponectin excretion appears to be an independent indicator of vascular damage potentially identifying an increased risk for vascular events. PMID:19509019

  13. Relationship of resistin levels with endometrial cancer risk.

    PubMed

    Hlavna, M; Kohut, L; Lipkova, J; Bienertova-Vasku, J; Dostalova, Z; Chovanec, J; Vasku, A

    2011-01-01

    Cancer of endometrium (CAE) is the most common gynecologic malignancy in industrialized nations. Increased resistin levels, an adipocytokine produced by adipose tissue and macrophages, have been considered as a risk factor in gastric, colon and breast cancer, recently. No studies associating resistin levels with endometrial cancer have been done so far. The purpose of this case-control study was to determine the relationship between serum circulating resistin levels and resistin gene -420C>G (rs3219175) variant in endometrial cancer patients. 37 Caucasian female patients and 39 healthy controls were enrolled in this study. Difference in resistin levels between age and BMI matched patients group (mean 24.2 ng/ml) and control subjects (mean 10.1 ng/ml) were statistically significant (p <001). We also determined single nucleotide polymorphism -420C>G (rs3219175) within resistin gene and no significant association between resistin levels and investigated polymorphism was found. Furthermore, no significant association between higher resistin levels and diabetes mellitus 2, body mass index, smoking or age have been observed within studied groups. To our knowledge, this is the first study examining the relationship between serum resistin levels and endometrial cancer and our results show, that patients with endometrial cancer have significantly increased circulating levels of resistin compared to control subjects. PMID:21275461

  14. Adiponectin promotes syncytialisation of BeWo cell line and primary trophoblast cells

    PubMed Central

    2010-01-01

    Background In human pregnancy, a correct placentation depends on trophoblast proliferation, differentiation, migration and invasion. These processes are highly regulated by placental hormones, growth factors and cytokines. Recently, we have shown that adiponectin, an adipokine, has anti-proliferative effects on trophoblastic cells. Here, we complete this study by demonstrating that adiponectin modulates BeWo and human villous cytotrophoblast cell differentiation. Results We showed that hCG secretion was up-regulated by adiponectin treatment in both BeWo cells and human cytotrophoblasts from very early placentas (5-6 weeks). The expression of two trophoblast differentiation markers, leptin and syncytin 2, was also up-regulated by adiponectin in BeWo cells. Moreover, adiponectin treatment induced a loss of E-cadherin staining in these cells. In parallel, we demonstrated that AdipoR1 and AdipoR2 are up-regulated during forskolin induced BeWo cell differentiation, reinforcing the role of adiponectin in trophoblast syncytialization. SiRNA mediated down-regulation of AdipoR1 and AdipoR2 was used to demonstrate that adiponectin effects on differentiation were essentially mediated by these receptors. Finally, using a specific inhibitor, we demonstrated that the PKA signalling pathway could be one pathway involved in adiponectin effects on trophoblast differentiation. Conclusion Adiponectin enhances the differentiation process of trophoblast cells and could thus be involved in functional syncytiotrophoblast formation. PMID:21034435

  15. Serum Adiponectin Level May be an Independent Predictor of Clear Cell Renal Cell Carcinoma

    PubMed Central

    Wang, Hongkai; Wu, Junlong; Gu, Weijie; Wang, Beihe; Wan, Fangning; Dai, Bo; Zhang, Hailiang; Shi, Guohai; Shen, Yijun; Zhu, Yiping; Zhu, Yao; Ye, Dingwei

    2016-01-01

    Objectives: To examine whether serum adiponectin or leptin level has the ability to differentiate clear cell renal cell carcinoma (ccRCC) from other subtypes of renal cell carcinoma (RCC) in a Chinese population. Patients and methods: We recruited 198 consecutive patients who were treated with radical or partial nephrectomy in our department from September 2011 to June 2013. Their histological types were all malignant, including clear cell, papillary, chromophobe and unclassified RCC. We also enrolled 86 people with no cancer or cancer-related diseases as normal controls. We measured patients' preoperative blood samples for plasma adiponectin and leptin concentrations using an enzyme-linked immunosorbent assay method. Statistical methods were used to analyze ccRCC and other subtypes as they relate to serum adiponectin/leptin level and other factors such as body mass index or visceral fat area. Results: In our database, normal controls had significantly higher circulating adiponectin (p < 0.001) and leptin levels (p < 0.001) than patients with RCC. Among the 198 RCC patients, 156 patients had ccRCC while 42 patients had other histological types. Serum adiponectin levels were lower in ccRCC patients than in non-clear-cell RCC patients (p = 0.004). However, the plasma leptin level was not differently distributed between ccRCC and non-ccRCC patients (p = 0.940). In multivariate analysis, we found that serum adiponectin level may be an independent predictor for discriminating ccRCC patients from others (p = 0.004). Furthermore, in the ccRCC subgroup, we observed that men with ccRCC had lower leptin (p < 0.001) and adiponectin (p = 0.002) levels, and diabetic patients had lower plasma adiponectin levels (p = 0.001). Conclusions: Lower plasma adiponectin concentration was related to an increased incidence of ccRCC and may act as an independent predictor for ccRCC. Our study may help define the process from obesity to adipose tissue, to cytokines and finally to ccRCC. PMID

  16. Resistin-like molecule α decreases glucose tolerance during intestinal inflammation1

    PubMed Central

    Munitz, Ariel; Seidu, Luqman; Cole, Eric T; Ahrens, Richard; S, Simon P Hogan; Rothenberg, Marc E

    2008-01-01

    Resistin-like molecule α (Relm-α), is a secreted cysteine-rich protein belonging to a newly defined family of proteins including resistin, Relm-β and Relm-γ. Resistin was initially defined based on its insulin resistance activity, but the family members are highly upregulated in various inflammatory states, especially those involving intestinal inflammation. Herein, we report the role of Relm-α at baseline and following an experimental model of colitis. Relm-α was readily detected in the serum at baseline (4−5 ng/ml) and its level was regulated by energy uptake. Retnla−/− mice had decreased baseline circulating leptin levels but displayed normal glucose, glucose clearance and insulin levels. Following exposure to the oral innate trigger dextran sodium sulfate (DSS), a non-redundant pro-inflammatory role for Relm-α was uncovered as Retnla−/− mice were markedly protected from DSS-induced disease activity and histopathological features. Relm-α regulated eosinophil-directed cytokines (e.g. IL-5, CCL11/eotaxin-1 and CCL5/RANTES) ex vivo. Consistently, DSS-treated Retnla−/− mice displayed substantially decreased eosinophil accumulation and decreased phosphorylation of NFκB, ERK1/2 and p38 in macrophages and eosinophils. Following DSS exposure, serum level of Relm-α was upregulated and DSS-treated Retnla−/− mice were markedly protected from hyperglycemia induced by glucose injection independent of changes in insulin levels. Retnla−/− mice were protected from increases in gut hormone serum levels of gastric inhibitory polypeptide and peptide YY that were induced following DSS-treatment. These findings demonstrate a central pro-inflammatory role for Relm-α in the regulation of colonic inflammation and a novel link between colonic injury, glucose tolerance and energy intake. PMID:19201890

  17. Low levels of adiponectin predict worsening of arterial morphology and function.

    PubMed

    Störk, Stefan; Bots, Michiel L; Angerer, Peter; von Schacky, Clemens; Grobbee, Diederick E; Angermann, Christiane E; Seufert, Jochen

    2007-10-01

    Adipocytokines are under investigation as mediators of cardiovascular risk. In 142 non-diabetic postmenopausal women, we investigated whether plasma levels of adiponectin and leptin are associated with changes in carotid intima-media thickness (IMT) and distensibility as assessed by high-resolution ultrasound. Adiponectin but not leptin correlated weakly with baseline measures of IMT and distensibility. After 12 months, carotid IMT showed a significant progression [0.023 mm (95% CI, 0.014-0.031 mm)] whereas stiffness was unaltered. A threshold was identified for the relation of adiponectin with both progression of IMT and stiffness. Age-adjusted adiponectin levels in the lowest quartile versus second to fourth quartile were related to progression of IMT (odds ratio, 2.99; 95% CI, 1.81-5.09) and stiffness (odds ratio, 1.71; 95% CI, 1.19-4.07). Adjustment for possible confounding factors and intermediates weakened this association only to a minor degree. No such associations were observed for leptin. We conclude that low levels of adiponectin are associated with adverse changes in morphology and function of central arteries over time independently of other cardiovascular risk factors in postmenopausal non-diabetic women. PMID:17239889

  18. Resistin is a survival factor for porcine ovarian follicular cells.

    PubMed

    Rak, Agnieszka; Drwal, Eliza; Wróbel, Anna; Gregoraszczuk, Ewa Łucja

    2015-10-01

    Previously, we demonstrated the expression of resistin in the porcine ovary, the regulation of its expression and its direct effect on ovarian steroidogenesis. The objective of this study was to examine the effect of resistin on cell proliferation and apoptosis in a co-culture model of porcine granulosa and theca cells. First, we analysed the effect of resistin at 1 and 10  ng/ml alone or in combination with FSH- and IGF1 on ovarian cell proliferation with an alamarBlue assay and protein expression of cyclins A and B using western blot. Next, the mRNA and protein expression of selected pro-apoptotic and pro-survival regulators of cell apoptosis, caspase-9, -8 and -3 activity and DNA fragmentation using real time PCR, western blot, fluorescent assay and an ELISA kit, respectively, were analysed after resistin treatment. Furthermore, we determined the effect of resistin on the protein expression of ERK1/2, Stat and Akt kinase. Using specific inhibitors of these kinases, we also checked caspase-3 activity and protein expression. We found that resistin, at both doses, has no effect on cell proliferation. The results showed that resistin decreased pro-apoptotic genes, which was confirmed on protein expression of selected factors. We demonstrate an inhibitory effect of resistin on caspase activity and DNA fragmentation. Finally, resistin stimulated phosphorylation of the ERK1/2, Stat and Akt and kinases inhibitors reversed resistin action on caspase-3 activity and protein expression to control. All of these results showed that resistin has an inhibitory effect on porcine ovarian cell apoptosis by activation of the MAPK/ERK, JAK/Stat and Akt/PI3 kinase signalling pathways. PMID:26159832

  19. Review: adiponectin in retinopathy.

    PubMed

    Fu, Zhongjie; Gong, Yan; Löfqvist, Chatarina; Hellström, Ann; Smith, Lois E H

    2016-08-01

    Neovascular eye diseases are a major cause of blindness including retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration in which new vessel formation is driven by hypoxia or metabolic abnormalities affecting the fuel supply. White-adipose-tissue derived adipokines such as adiponectin modulate metabolic responses. Increasing evidence shows that lack of adiponectin may result in retinal neovascularization. Activation of the adiponectin pathway may in turn restore energy metabolism, to suppress the drive for compensatory but ultimately pathological neovessels of retinopathy. In this review, we will summarize our current knowledge of the role of adiponectin in eye diseases of premature infants, diabetic patients as well as the elderly. Further investigations in this field are likely to lead to new preventative approaches for these diseases. PMID:27155572

  20. Resistin: functional roles and therapeutic considerations for cardiovascular disease

    PubMed Central

    Jamaluddin, Md S; Weakley, Sarah M; Yao, Qizhi; Chen, Changyi

    2012-01-01

    Resistin, originally described as an adipocyte-specific hormone, has been suggested to be an important link between obesity, insulin resistance and diabetes. Although its expression was initially defined in adipocytes, significant levels of resistin expression in humans are mainly found in mononuclear leukocytes, macrophages, spleen and bone marrow cells. Increasing evidence indicates that resistin plays important regulatory roles apart from its role in insulin resistance and diabetes in a variety of biological processes: atherosclerosis and cardiovascular disease (CVD), non-alcoholic fatty liver disease, autoimmune disease, malignancy, asthma, inflammatory bowel disease and chronic kidney disease. As CVD accounts for a significant amount of morbidity and mortality in patients with diabetes and without diabetes, it is important to understand the role that adipokines such as resistin play in the cardiovascular system. Evidence suggests that resistin is involved in pathological processes leading to CVD including inflammation, endothelial dysfunction, thrombosis, angiogenesis and smooth muscle cell dysfunction. The modes of action and signalling pathways whereby resistin interacts with its target cells are beginning to be understood. In this review, the current knowledge about the functions and pathophysiological implications of resistin in CVD development is summarized; clinical translations, therapeutic considerations and future directions in the field of resistin research are discussed. LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3 PMID:21545576

  1. Adiponectin and the systemic inflammatory response in weight-losing patients with non-small cell lung cancer.

    PubMed

    Jamieson, Nigel B; Brown, Duncan J F; Michael Wallace, A; McMillan, Donald C

    The aim of the present study was to examine the relationship between adiponectin and the systemic inflammatory response in weight-losing patients with non-small cell lung cancer (NSCLC). Measurement of anthropometry, acute phase proteins, interleukin-6, leptin (total and free) and adiponectin were carried out on healthy subjects (n = 13) and non-small cell lung cancer patients with weight loss (n = 20). The groups were age and sex matched. Compared with the controls the cancer group had a lower BMI (p < 0.01), mid-upper arm circumference (p < 0.001), triceps skinfold thickness (p < 0.05) and circulating concentrations of albumin (p < 0.001), haemoglobin (p < 0.05), free and total leptin (p < 0.05) and adiponectin (p < 0.01). In contrast, the cancer group had elevated circulating concentrations of interleukin-6 and C-reactive protein concentrations (p < 0.001). In the cancer group circulating adiponectin concentrations were significantly inversely correlated with both free (rs = -0.675, p = 0.001) and total leptin concentrations (rs = -0.690, p = 0.001). However, neither weight loss, interleukin-6 or C-reactive protein concentrations were correlated with either adiponectin, free or total leptin concentrations in the cancer group. These results suggest that adipokine production is normal and is unlikely to play a major role in the abnormal fat metabolism in weight-losing cancer patients. PMID:15242698

  2. Milk Leptin Surge and Biological Rhythms of Leptin and Other Regulatory Proteins in Breastmilk

    PubMed Central

    Nozhenko, Yuriy; Asnani-Kishnani, Madhu; Rodríguez, Ana M.; Palou, Andreu

    2015-01-01

    A significant number of chronic diseases are linked to perinatal nutrition, and prevention may be associated to naturally occurring components of breast milk. One key hormone in breast milk is leptin, related with the protection from obesity in the adulthood, thus knowing its changes through the day or lactation is crucial. We aimed to investigate the daily rhythms in the milk levels of leptin, together with other two related hormones, ghrelin and adiponectin, during lactation (days 5, 10 and 15) in rat dams, and the relation with morphometric parameters (dams and pups). Summarizing the main results, the existence of biological rhythms, but not daily and maybe circasemidian, was confirmed for the three hormones at the earliest period of lactation. The correlations performed generally showed a possible dependence of milk hormone levels on plasma levels at the early phase of lactation, while with the progression of lactation this dependence may fade and the hormone levels are suggested to be more dependent on mammary gland production/maturation. There was also a correlation between milk leptin and adiponectin levels, especially in the first half of lactation, suggesting a possible parallel regulation. Interestingly, we describe a milk leptin surge around the mid of lactation (at day 10) which may be related with pup´s growth (males and females) and with the well-known (in the literature) plasma leptin surge in pups. All this knowledge may be crucial for future applications in the development of formula milk and in relation with the role of leptin surge during lactation. PMID:26680765

  3. Clinical aspects of leptin.

    PubMed

    Sinha, M K; Caro, J F

    1998-01-01

    Hyperleptinemia is an essential feature of human obesity. Total body fat mass > % body fat > BMI are the best predictors of circulating leptin levels. Although ob gene is differentially expressed in different fat compartments, apart from total body fat, upper or lower body adiposity or visceral fat does not influence basal leptin levels. Similarly, age, basal glucose levels, and ethnicity do not influence circulating leptin levels. Only in insulin-sensitive individuals do basal levels of insulin and leptin correlate positively even after factoring in body fat. Diabetes does not influence leptin secretion in both lean and obese subjects per se. Independent of adiposity, leptin levels are higher in women than in men. This sexual dimorphism is also present in adolescent children. In eating disorders anorexia nervosa and bulimea nervosa, leptin levels are not upregulated but simply reflect BMI and probably body fat. In spite of strong correlation between body fat and leptin levels, there is great heterogeneity in leptin levels at any given index of body fat. About 5% of obese populations can be regarded as "relatively" leptin deficient which could benefit from leptin therapy. Leptin has dual regulation in human physiology. During the periods of weight maintenance, when energy intake and energy output are equal, leptin levels reflect total bodyfat mass. However, in conditions of negative (weight-loss programs) and positive (weight-gain programs) energy balances, the changes in leptin levels function as a sensor of energy imbalance. This latter phenomenon is best illustrated by short-term fasting and overfeeding experiments. Within 24 h of fasting leptin levels decline to approximately 30% of initial basal values. Massive overfeeding over a 12-h period increases leptin levels by approximately 50% of initial basal values. Meal ingestion does not acutely regulate serum leptin levels. A few studies have shown a modest increase in leptin secretion at supraphysiological

  4. Circulating resistin protein and mRNA concentrations and clinical severity of coronary artery disease

    PubMed Central

    Sopic, Miron; Spasojevic-Kalimanovska, Vesna; Kalimanovska-Ostric, Dimitra; Andjelkovic, Kristina; Jelic-Ivanovic, Zorana

    2015-01-01

    Introduction Previous studies have implicated a strong link between circulating plasma resistin and coronary artery disease (CAD). The aim of this study was to evaluate the differences in peripheral blood mononuclear cells (PBMC) resistin mRNA and its plasma protein concentrations between the patients with CAD of different clinical severity. Material and methods This study included 33 healthy subjects as the control group (CG) and 77 patients requiring coronary angiography. Of the latter 30 was CAD negative whereas 47 were CAD positive [18 with stable angina pectoris (SAP) and 29 with acute coronary syndrome (ACS)]. Circulating resistin was measured by ELISA; PBMC resistin mRNA was determined by real-time PCR. Results Resistin protein was significantly higher in the ACS group compared to the CG (P = 0.001) and the CAD negative group (P = 0.018). Resistin mRNA expression did not vary across the study groups, despite the positive correlation seen with plasma resistin (ρ = 0.305, P = 0.008). In patients, plasma resistin and PBMC resistin mRNA negatively correlated with HDL-C (ρ = -0.404, P < 0.001 and ρ = -0.257, P = 0.032, respectively). Furthermore, the highest plasma resistin tertile showed the lowest HDL-C (P = 0.006). Plasma resistin was positively associated with serum creatinine (ρ = 0.353, P = 0.002). Conclusion Significant increase of plasma resistin in patients with ACS compared to CG and CAD negative patients was observed. Despite no change in PBMC resistin mRNA in different disease conditions a positive association between resistin mRNA and resistin plasma protein was evident. Both plasma resistin and PBMC resistin mRNA were negatively associated with plasma HDL-C, and plasma resistin positively with serum creatinine. PMID:26110037

  5. Heparanase Interacts with Resistin and Augments Its Activity

    PubMed Central

    Novick, Daniela; Barak, Sara; Ilan, Neta; Vlodavsky, Israel

    2014-01-01

    In an attempt to isolate a heparanase receptor, postulated to mediate non-enzymatic functions of the heparanase protein, we utilized human urine collected from healthy volunteers. Affinity chromatography of this rich protein source on immobilized heparanase revealed resistin as a heparanase binding protein. Co-immunoprecipitation and ELISA further confirmed the interaction between heparanase and resistin. Importantly, we found that heparanase potentiates the bioactivity of resistin in its standard bioassay in which monocytic human leukemia cell line, THP1, differentiates into adherent macrophage-like foam cells. It is thus conceivable that this newly identified complex of heparanase and resistin exerts a stimulatory effect also in various inflammatory conditions known to be affected by the two proteins. PMID:24465803

  6. Neutrophil-derived resistin release induced by Aggregatibacter actinomycetemcomitans.

    PubMed

    Furugen, Reiko; Hayashida, Hideaki; Yoshii, Yumiko; Saito, Toshiyuki

    2011-08-01

    Resistin is an adipokine that induces insulin resistance in mice. In humans, resistin is not produced in adipocytes, but in various leukocytes instead, and it acts as a proinflammatory molecule. The present investigation demonstrated high levels of resistin in culture supernatants of neutrophils that are stimulated by a highly leukotoxic strain of Aggregatibacter actinomycetemcomitans. In contrast, the level of resistin was remarkably low when neutrophils were exposed to two other strains that produce minimal levels of leukotoxin and a further isogenic mutant strain incapable of producing leukotoxin. Pretreatment of neutrophils with a monoclonal antibody to CD18, β chain of lymphocyte function-associated molecule 1 (LFA-1), or an Src family tyrosine kinase inhibitor before incubation with the highly leukotoxic strain inhibited the release of resistin. These results show that A. actinomycetemcomitans-expressed leukotoxin induces extracellular release of human neutrophil-derived resistin by interacting with LFA-1 on the surface of neutrophils and, consequently, activating Src family tyrosine kinases. PMID:21658109

  7. Leptin in end stage renal disease (ESRD): a link between fat mass, bone and the cardiovascular system.

    PubMed

    Mallamaci, F; Tripepi, G; Zoccali, C

    2005-01-01

    Adipose tissue is now considered an important system operating strictly in concert with other systems. The adipocyte is the main producer of two pleiotropic compounds, leptin and adiponectin, modulating inflammation and having multiple effects in disparate organs including the cardiovascular and the central nervous system. Leptin has disparate influences on various physiologic and organ systems including glucose homeostasis, hematopoiesis and the reproductive and cardiovascular systems and is a crucial hormone for the regulation of food intake and body weight. Peripherally, leptin modulates insulin sensitivity and high leptin triggers insulin resistance and vice versa. Obesity, a situation where circulating leptin attains very high levels is accompanied by increased bone mass, a phenomenon which may depend on direct stimulation of osteoblasts by leptin. However in animal models the stimulating effect of leptin on the osteoblast is counterbalanced by a strong inhibitor effect on bone formation in the central nervous system. Two recent studies reported an inverse link between leptin, bone mass and PTH in dialysis patients suggesting that leptin may be implicated in low bone turnover in these patients, likely by a mechanism involving the central nervous system. Leptin induces vascular calcifications in vitro. In uremic man leptin is unrelated to valvular calcifications but predicts incident cardiovascular events in overweight and obese dialysis patients. Leptin seems to be a relevant player in the emerging connection between bone and cardiovascular alterations in patients with end stage renal disease. PMID:16245256

  8. Associations of Single Nucleotide Polymorphisms in the Adiponectin Gene with Adiponectin Levels and Cardio-Metabolic Risk Factors in Patients with Cancer

    PubMed Central

    Al Khaldi, Rasha Mazen; Al Mulla, Fahd; Al Awadhi, Shafika; Kapila, Kusum; Mojiminiyi, Olusegun A.

    2011-01-01

    Objectives: The aims of this study are to (1) study the influence of polymorphisms in adiponectin gene on adiponectin levels and potential associations with breast, prostate and colon cancer; (2) investigate the associations of adiponectin levels with other adipokines and breast, prostate and colon cancers. Subjects: We measured fasting adiponectin, leptin, insulin, Sex steroids in 132 (66 females, 66 males) cancer patients and 68 age and sex matched apparently healthy subjects. Body Mass Index (BMI) and waist circumference were used as indices of obesity. Insulin Resistance was assessed using Homeostasis Model Assessment (HOMA). Three single nucleotide polymorphisms (SNP rs182052 (G-10066-A), SNP rs1501299 (276G > T), SNP rs224176 (45T > G) in adiponectin gene were studied using Real Time Polymerase Chain Reaction. Results: GG genotype of SNP rs1501299 was significantly associated with higher levels of adiponectin (OR=1.2, 95%CI(1.03–1.3), p = 0.02); breast (OR=8.6, 95%CI(1.03–71), p = 0.04), colon cancers (OR= 12, 95%CI(1.2–115), p = 0.03). GT genotype was also associated significantly with colon cancer (OR=2.6, 95%CI (1.1–6), p = 0.03). However SNP rs224176 was associated with only breast cancer. Conclusion: Our results demonstrate that adiponectin gene SNP rs1501299 and SNP rs224176 may be the predisposing factors in some cancers but our results differ from what has been reported in other populations suggesting a complex relationship between genetic variations and phenotypic adiponectin levels. PMID:21694446

  9. Cross-tissue comparisons of leptin and adiponectin

    PubMed Central

    Houde, Andrée-Anne; Légaré, Cécilia; Hould, Frédéric-Simon; Lebel, Stéfane; Marceau, Picard; Tchernof, André; Vohl, Marie-Claude; Hivert, Marie-France; Bouchard, Luigi

    2014-01-01

    DNA methylation has been mostly studied in circulating blood cells. Although being readily accessible, metabolically active tissues such as adipose tissue would be more informative for the study of metabolic disorders. However, whether or not the blood DNA methylation profile correlates with that of adipose tissue remains unknown. In this study, DNA methylation patterns of variation at LEP and ADIPOQ gene loci were similar between individual CpGs across the different tissues. We also report that DNA methylation levels at biologically relevant CpGs are correlated between blood, subcutaneous, and visceral adipose tissue, and that these nearby CpGs are associated with LEP and ADIPOQ gene expression in adipose tissues. These results will be highly relevant for future epigenetic studies in metabolic disorders. PMID:24719787

  10. Blood leptin and C-reactive protein provide more sensitive assessment than blood lipids and other inflammatory biomarkers in overweight university students.

    PubMed

    Wang, Shu; Reed, Debra B; Goli, Srikanth; Goswami, Debalina

    2011-08-01

    Overweight is an inflammatory disease, and today's overweight university students will be tomorrow's overweight employees and parents; however, few studies have focused on the link between overweight and inflammation in university students. We hypothesized that students at higher body mass index (BMI) and percent body fat (BF%) would have higher blood concentrations of lipids and inflammatory biomarkers. A cross-sectional study including 110 university students was conducted at Texas Tech University. Overweight was determined by BMI using measured height and weight, and BF% was determined using bioelectric impedance analysis. Serum triglyceride and cholesterol concentrations were measured using enzymatic methods. Plasma concentrations of leptin, adiponectin, C-reactive protein (CRP), interleukin-6, and tumor necrosis factor α were measured using an enzyme-linked immunosorbent assay. Our results showed that higher BMI was associated with increased blood concentrations of CRP, leptin, and triglyceride (only in male subjects) and decreased blood adiponectin concentrations in university students. In addition, BF% was significantly correlated with blood concentrations of leptin and CRP. Female students had significantly higher blood concentrations of leptin, adiponectin, and CRP than did male students. In conclusion, blood inflammatory biomarkers, especially leptin and CRP, provide a more sensitive and accurate assessment than blood cholesterol and triglyceride for overweight individuals in this population. Leptin, adiponectin, and CRP are sex-dependent inflammatory biomarkers. PMID:21925343

  11. Circulating leptin and NF-κB activation in peripheral blood mononuclear cells across the menstrual cycle.

    PubMed

    Faustmann, Gernot; Tiran, Beate; Maimari, Theopisti; Kieslinger, Petra; Obermayer-Pietsch, Barbara; Gruber, Hans-Jürgen; Roob, Johannes M; Winklhofer-Roob, Brigitte M

    2016-07-01

    Using the menstrual cycle as a model, this study focused on longitudinal changes and associations within a physiological network known to play a role in female fertility, including, as biologically active nodes, NF-κB, leptin and adiponectin, β-carotene, adipose tissue, and progesterone. In 28 women, leptin, adiponectin, β-carotene, and progesterone concentrations, NF-κB p65 and p50 activation in peripheral blood mononuclear cells (known to possess estrogen, progesterone and leptin receptors), total body fat (TBF) and subcutaneous adipose tissue (SAT) mass were determined at early (T1) and late follicular (T2) and mid (T3) and late (T4) luteal phase. Leptin and adiponectin concentrations were higher, while NF-κB p65 activation was lower at T3 compared with T1. NF-κB p65 activation was inversely related to leptin concentrations at T1, T3, and T4. β-Carotene was inversely related to leptin (T1,T2,T4) and SAT (T1,T3,T4). NF-κB p50 activation was inversely related to TBF (T4) and SAT (T3,T4), and leptin was positively related to TBF and SAT (T1-T4). Progesterone was inversely related to leptin (T2,T3), adiponectin (T3), TBF (T3,T4), and SAT (T2,T3,T4). By providing evidence of luteal phase-specific reduced NF-κB p65 activation in women under physiological conditions, this study bridges the gap between existing evidence of a Th1-Th2 immune response shift induced by reduced NF-κB p65 activation and a Th1-Th2 shift previously observed at luteal phase. For the first time, inverse regressions suggest inhibitory effects of leptin on NF-κB p65 activation at luteal phase, along with inhibitory effects of leptin as well as adiponectin on progesterone production in corpus luteum. © 2016 The Authors BioFactors published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology. 24(4):376-387, 2016. PMID:27093900

  12. 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.

  13. Leptin and pregnancy outcome.

    PubMed

    Kratzsch, J; Höckel, M; Kiess, W

    2000-12-01

    Leptin, a recently discovered hormone that is involved in the regulation of body weight, appears to be one of the hormonal factors that signal the body's readiness for sexual maturation and reproduction to the brain. The present review focuses on clinical and experimental studies that describe the roles of maternal and foetal leptin as predictive factors for the physiological and pathophysiological development of the foetus during pregnancy, assisted reproduction and neonatal life. Through evaluating alterations of maternal serum leptin levels, a physiological hyperleptinaemia has been observed to occur, particularly during the second and third trimesters of pregnancy, which is not associated with a decreased food intake or reduced metabolic activity in the pregnant women. This state of leptin resistance is comparable to the condition in obesity. In contrast, hypoleptinaemia is suggested to be an indicator for the cessation of pregnancy, either naturally at term or as a result of pathology at any time during gestation. Thus, an appropriate maternal leptin level seems to be a prerequisite for a normal pregnancy. The main source of foetal leptin is the still immature foetal adipose tissue. As intrauterine growth has been found to be independently associated with cord blood leptin level, it has been suggested that leptin plays a role as a regulator of foetal growth. During assisted reproduction cycles leptin levels in the follicular fluid of patients may be also of predictive value, with low levels predicting therapeutic failure. Finally, the relevance of leptin to postnatal development is reviewed; leptin may be important for regulation of satiety and peripheral metabolism. In summary, leptin appears to be an important permissive factor that is involved in female reproduction. PMID:11128413

  14. Serum resistin levels in children with primary snoring.

    PubMed

    Zicari, A M; Cutrera, R; Occasi, F; Carbone, M P; Cesoni Marcelli, A; De Castro, G; Indinnimeo, L; Tancredi, G; Galandrini, R; Giuffrida, A; Duse, M

    2014-01-01

    Primary Snoring (PS) has been positioned at the milder end of the Sleep-Disordered Breathing severity continuum characterized by snoring and it is usually underestimated. PS is defined as snoring without apnea, frequent arousals, or gas exchange abnormalities and recent studies demonstrated that children with PS have increased blood pressure and reduced arterial distensibility. The association between adipokines and SDB has been recently investigated, though most of the studies were focused on OSAS where intermittent hypoxia characterizing the disease may lead to an inflammatory cascade and to the release of several adipokines, contributing to oxidative stress. Resistin, initially described s an adipokine increasing insulin resistance, has been recently identified as a novel important member of the cytokine family involved in the regulation of inflammation. The aim of our study was to investigate circulating resistin levels in normal weight children with PS. Sixty-five children of normal weight aged between 4 and 14 years of age were selected for habitual snoring. Children with positive polysomnography were excluded from the study. Serum resistin levels were detected in all children with PS. Thirty-three healthy non-snorer children with similar age, sex and BMI were selected as a control group. A significantly higher level of resistin was observed in patients with PS compared to the control group (4.67±1.91 ng/ml vs 3.98±1.58 ng/ml; p<0.01). Patients with inconclusive pulse oximetry showed significantly higher resistin levels than those with negative recordings recordings (5.29±1.91 ng/ml vs 4.20±1.93 ng/ml; p<0.008). Moreover, there was a significant increasing trend between sieric adipokine level and the frequency of snoring (p<0.006). Our results suggest that systemic inflammation and oxidative stress may also play a significant role in the pathophysiology of PS. PMID:25280038

  15. Resistin: a potential biomarker for periodontitis influenced diabetes mellitus and diabetes induced periodontitis.

    PubMed

    Devanoorkar, Archana; Kathariya, Rahul; Guttiganur, Nagappa; Gopalakrishnan, D; Bagchi, Paulami

    2014-01-01

    Biomarkers are highly specific and sensitive indicators of disease activity. Resistin is a recently discovered adipocytokine, having a potent biomarker quality. Initially resistin was thought to be produced by adipocytes alone; however, emerging evidence suggests that it is also produced in abundance by various cells of the immunoinflammatory system, indicating its role in various chronic inflammatory diseases. Data suggests that resistin plays a role in obesity, insulin resistance, cardiovascular diseases, and periodontitis. Resistin derived its name from the original observation that it induced insulin resistance (resist-in: resist insulin) in mice and is downregulated in mature murine adipocytes cultured in the presence of insulin sensitizing drugs like thiazolidinediones. It is well recognized that obesity, is associated with insulin resistance and diabetes. A three-way relationship has been established between diabetes, obesity and periodontitis. Recent evidence also suggests an association between obesity and increased risk for periodontitis. Our previous research showed incremental elevation of resistin with periodontal disease activity and a reduced level of resistin, after periodontal therapy. Thus resistin would be one of the molecular links connecting obesity, periodontitis, and diabetes and may serve as a marker that links periodontal disease with other systemic diseases. A Medline/PubMed search was carried out for keywords "Diabetes Mellitus," "Periodontitis," and "Resistin," and all relevant research papers from 1990 in English were shortlisted and finalized based on their importance. This review provides an insight into the biological action of resistin and its possible role in periodontitis influenced diabetes mellitus and diabetes induced periodontitis. PMID:24692844

  16. [The diversity of leptin].

    PubMed

    Mai, Knut

    2015-12-01

    The role of leptin in regulation of energy homeostasis is well established, yet both the diagnostic as well as the therapeutic relevance of leptin in diet-induced obesity remains unresolved. Nevertheless, in the last few years, the substantial impact of leptin substitution in selected forms of monogenic obesity has advanced our knowledge about the neuroendocrine network of body weight regulation. Moreover, leptin seems to play a crucial role in intestinal nutrient reabsorption, regulation of blood pressure, fertility, inflammation and autoimmune diseases. A better understanding of these processes could possibly provide novel diagnostic and therapeutic options in the future. PMID:26625227

  17. Elevated Resistin Gene Expression in African American Estrogen and Progesterone Receptor Negative Breast Cancer

    PubMed Central

    Vallega, Karin A.; Liu, NingNing; Myers, Jennifer S.; Yu, Kaixian; Sang, Qing-Xiang Amy

    2016-01-01

    Introduction African American (AA) women diagnosed with breast cancer are more likely to have aggressive subtypes. Investigating differentially expressed genes between patient populations may help explain racial health disparities. Resistin, one such gene, is linked to inflammation, obesity, and breast cancer risk. Previous studies indicated that resistin expression is higher in serum and tissue of AA breast cancer patients compared to Caucasian American (CA) patients. However, resistin expression levels have not been compared between AA and CA patients in a stage- and subtype-specific context. Breast cancer prognosis and treatments vary by subtype. This work investigates differential resistin gene expression in human breast cancer tissues of specific stages, receptor subtypes, and menopause statuses in AA and CA women. Methods Differential gene expression analysis was performed using human breast cancer gene expression data from The Cancer Genome Atlas. We performed inter-race resistin gene expression level comparisons looking at receptor status and stage-specific data between AA and CA samples. DESeq was run to test for differentially expressed resistin values. Results Resistin RNA was higher in AA women overall, with highest values in receptor negative subtypes. Estrogen-, progesterone-, and human epidermal growth factor receptor 2- negative groups showed statistically significant elevated resistin levels in Stage I and II AA women compared to CA women. In inter-racial comparisons, AA women had significantly higher levels of resistin regardless of menopause status. In whole population comparisons, resistin expression was higher among Stage I and III estrogen receptor negative cases. In comparisons of molecular subtypes, resistin levels were significant higher in triple negative than in luminal A breast cancer. Conclusion Resistin gene expression levels were significantly higher in receptor negative subtypes, especially estrogen receptor negative cases in AA

  18. Alterations in Mouse Hypothalamic Adipokine Gene Expression and Leptin Signaling following Chronic Spinal Cord Injury and with Advanced Age

    PubMed Central

    Bigford, Gregory E.; Bracchi-Ricard, Valerie C.; Nash, Mark S.; Bethea, John R.

    2012-01-01

    Chronic spinal cord injury (SCI) results in an accelerated trajectory of several cardiovascular disease (CVD) risk factors and related aging characteristics, however the molecular mechanisms that are activated have not been explored. Adipokines and leptin signaling are known to play a critical role in neuro-endocrine regulation of energy metabolism, and are now implicated in central inflammatory processes associated with CVD. Here, we examine hypothalamic adipokine gene expression and leptin signaling in response to chronic spinal cord injury and with advanced age. We demonstrate significant changes in fasting-induced adipose factor (FIAF), resistin (Rstn), long-form leptin receptor (LepRb) and suppressor of cytokine-3 (SOCS3) gene expression following chronic SCI and with advanced age. LepRb and Jak2/stat3 signaling is significantly decreased and the leptin signaling inhibitor SOCS3 is significantly elevated with chronic SCI and advanced age. In addition, we investigate endoplasmic reticulum (ER) stress and activation of the uncoupled protein response (UPR) as a biological hallmark of leptin resistance. We observe the activation of the ER stress/UPR proteins IRE1, PERK, and eIF2alpha, demonstrating leptin resistance in chronic SCI and with advanced age. These findings provide evidence for adipokine-mediated inflammatory responses and leptin resistance as contributing to neuro-endocrine dysfunction and CVD risk following SCI and with advanced age. Understanding the underlying mechanisms contributing to SCI and age related CVD may provide insight that will help direct specific therapeutic interventions. PMID:22815920

  19. Objectively Measured Physical Activity and Its Association With Adiponectin and Other Novel Metabolic Markers

    PubMed Central

    Metcalf, Brad S.; Jeffery, Alison N.; Hosking, Joanne; Voss, Linda D.; Sattar, Naveed; Wilkin, Terence J.

    2009-01-01

    OBJECTIVE—Recent evidence suggests that, in children, traditional markers of metabolic disturbance are related only weakly to physical activity. We therefore sought to establish the corresponding relationships with newer metabolic markers. RESEARCH DESIGN AND METHODS—This was a nonintervention longitudinal study of 213 healthy children recruited from 54 schools in Plymouth, U.K. MTI accelerometers were used to make objective 7-day recordings of physical activity at ages 5 ± 0.3 (mean ± SD), 6, 7, and 8 years. Overall physical activity was taken as the average of the four annual time points. The metabolic markers at 8 years were adiponectin, leptin, high-sensitivity C-reactive protein (hsCRP), and insulin resistance (homeostasis model assessment). Potential confounders included percent body fat measured by dual-energy X-ray absorptiometry and diet measured by food frequency questionnaire. RESULTS—Whereas physical activity did not correlate with insulin resistance (r = −0.01), leptin (r = +0.04), or hsCRP (r = +0.01) independently of percent body fat, it did correlate with adiponectin, but inversely (r = −0.18, P = 0.02). This unexpected inverse relationship was strongest among the less active children (physical activity < median: r = −0.30, P = 0.01) but negligible in the more active children (physical activity > median: r = +0.04, P = 0.76). Adiponectin was significantly higher (0.52 SD, P < 0.01) in the least active tertile compared with the other two tertiles. Insulin resistance, however, did not differ across the physical activity tertiles (P = 0.62). CONCLUSIONS—Adiponectin levels in children are highest among those who are least active, but their insulin resistance is no different. Adiponectin has a known insulin-sensitizing effect, and our findings are consistent with a selective effect at low levels of physical activity. PMID:19033408

  20. Right hippocampus size is negatively correlated with leptin serum levels in bipolar disorder.

    PubMed

    Vianna-Sulzbach, Miréia; Rocha, Natalia P; Teixeira, Antonio Lucio; Rosa, Eduarda D; Goldani, André A S; Kauer-Sant Anna, Marcia; Gama, Clarissa S

    2015-12-15

    Obesity is more frequent in bipolar disorder. Adipokines are associated with depression and obesity via the inflammatory process. Twenty-six DSM-IV patients with BD and 39 controls were enrolled to assess the relationship between serum leptin and adiponectin with hippocampal volumes. Among patients, there was a significant negative correlation between right hippocampal volume and serum leptin levels. This result sum for the hypothesis of a pro-inflammatory state associated with BD and the prevalent co-morbid obesity. PMID:26434408

  1. Resistin modulates glucose uptake and glucose transporter-1 (GLUT-1) expression in trophoblast cells

    PubMed Central

    Di Simone, Nicoletta; Di Nicuolo, Fiorella; Marzioni, Daniela; Castellucci, Mario; Sanguinetti, Maurizio; D’lppolito, Silvia; Caruso, Alessandro

    2009-01-01

    Abstract The adipocytokine resistin impairs glucose tolerance and insulin sensitivity. Here, we examine the effect of resistin on glucose uptake in human trophoblast cells and we demonstrate that transplacental glucose transport is mediated by glucose transporter (GLUT)-1. Furthermore, we evaluate the type of signal transduction induced by resistin in GLUT-1 regulation. BeWo choriocarcinoma cells and primary cytotrophoblast cells were cultured with increasing resistin concentrations for 24 hrs. The main outcome measures include glucose transport assay using [3H]-2-deoxy glucose, GLUT-1 protein expression by Western blot analysis and GLUT-1 mRNA detection by quantitative real-time RT-PCR. Quantitative determination of phospho(p)-ERK1/2 in cell lysates was performed by an Enzyme Immunometric Assay and Western blot analysis. Our data demonstrate a direct effect of resistin on normal cytotrophoblastic and on BeWo cells: resistin modulates glucose uptake, GLUT-1 messenger ribonucleic acid (mRNA) and protein expression in placental cells. We suggest that ERK1/2 phosphorylation is involved in the GLUT-1 regulation induced by resistin. In conclusion, resistin causes activation of both the ERK1 and 2 pathway in trophoblast cells. ERK1 and 2 activation stimulated GLUT-1 synthesis and resulted in increase of placental glucose uptake. High resistin levels (50–100 ng/ml) seem able to affect glucose-uptake, presumably by decreasing the cell surface glucose transporter. PMID:18410529

  2. Leptin and reproductive function.

    PubMed

    Hausman, Gary J; Barb, C Richard; Lents, Clay A

    2012-10-01

    Adipose tissue plays a dynamic role in whole-body energy homeostasis by acting as an endocrine organ. Collective evidence indicates a strong link between neural influences and adipocyte expression and secretion of leptin. Developmental changes in these relationships are considered important for pubertal transition in reproductive function. Leptin augments secretion of gonadotropin hormones, which are essential for initiation and maintenance of normal reproductive function, by acting centrally at the hypothalamus to regulate gonadotropin-releasing hormone (GnRH) neuronal activity and secretion. The effects of leptin on GnRH are mediated through interneuronal pathways involving neuropeptide-Y, proopiomelanocortin and kisspeptin. Increased infertility associated with diet induced obesity or central leptin resistance are likely mediated through the kisspeptin-GnRH pathway. Furthermore, Leptin regulates reproductive function by altering the sensitivity of the pituitary gland to GnRH and acting at the ovary to regulate follicular and luteal steroidogenesis. Thus leptin serves as a putative signal that links metabolic status with the reproductive axis. The intent of this review is to examine the biological role of leptin with energy metabolism, and reproduction. PMID:22980196

  3. Resistin, a fat-derived secretory factor, promotes metastasis of MDA-MB-231 human breast cancer cells through ERM activation

    PubMed Central

    Lee, Jung Ok; Kim, Nami; Lee, Hye Jeong; Lee, Yong Woo; Kim, Su Jin; Park, Sun Hwa; Kim, Hyeon Soo

    2016-01-01

    Resistin, an adipocyte-secreted factor, is known to be elevated in breast cancer patients. However, the molecular mechanism by which resistin acts is not fully understood. The aim of this study was to investigate whether resistin could stimulate invasion and migration of breast cancer cells. Here, we report that resistin stimulated invasion and migration of breast cancer cells as well as phosphorylation of c-Src. Inhibition of c-Src blocked resistin-induced breast cancer cell invasion. Resistin increased intracellular calcium concentration, and chelation of intracellular calcium blocked resistin-mediated activation of Src. Resistin also induced phosphorylation of protein phosphatase 2A (PP2A). Inhibition of c-Src blocked resistin-mediated PP2A phosphorylation. In addition, resistin increased phosphorylation of PKCα. Inhibition of PP2A enhanced resistin-induced PKCα phosphorylation, demonstrating that PP2A activity is critical for PKCα phosphorylation. Resistin also increased phosphorylation of ezrin, radixin, and moesin (ERM). Additionally, ezrin interacted with PKCα, and resistin promoted co-localization of ezrin and PKCα. Either inhibition of c-Src and PKCα or knock-down of ezrin blocked resistin-induced breast cancer cells invasion. Moreover, resistin increased expression of vimentin, a key molecule for cancer cell invasion. Knock-down of ezrin abrogated resistin-induced vimentin expression. These results suggest that resistin play as a critical regulator of breast cancer metastasis. PMID:26729407

  4. Adiponectin as a target for the treatment of nonalcoholic steatohepatitis with thiazolidinediones: A systematic review.

    PubMed

    Polyzos, Stergios A; Mantzoros, Christos S

    2016-09-01

    Thiazolidinediones (TZDs; pioglitazone and rosiglitazone) have provided promising results in clinical trials for nonalcoholic steatohepatitis (NASH). The main purpose of this systematic review was to summarize evidence on circulating adiponectin levels in relation to histological changes following TZD treatment in patients with histologically confirmed NASH. We performed a systematic search in PubMed, Scopus and Cochrane Library. We included four studies, published between 2006 and 2012, providing data for 187 histologically confirmed NASH adult patients (105 on TZD and 82 controls) treated for 6-12months. Significant increase in adiponectin (80-178%) after TZD treatment was observed in all included studies. Improvement in steatosis following treatment was observed in all studies. A trend towards improvement in lobular inflammation was observed in all studies after pioglitazone, but not after rosiglitazone. Trends toward improvement in ballooning and fibrosis were observed in the two studies after pioglitazone using either the highest doses or the longest duration of therapy. Overall disease activity score was improved in all studies after pioglitazone, but not after rosiglitazone. Insulin resistance and liver function tests were also improved after treatment. Despite weight gain, circulating leptin was not increased after treatment. In conclusion, parallel increases in circulating adiponectin levels and histological improvement were observed in this systematic review. These results warrant further consideration of TZDs, but even more importantly point to a key role for novel potential treatments for NASH patients such as the newer selective peroxisome proliferator activated receptor-γ modulators, which increase adiponectin without significant weight gain. PMID:27506737

  5. Adipokine profile in celiac patients: differences in comparison with patients suffering from diarrhea-predominant IBS and healthy subjects.

    PubMed

    Russo, Francesco; Chimienti, Guglielmina; Clemente, Caterina; D'Attoma, Benedetta; Linsalata, Michele; Orlando, Antonella; De Carne, Massimo; Cariola, Filomena; Semeraro, Francesco P; Pepe, Gabriella; Riezzo, Giuseppe

    2013-12-01

    OBJECTIVE. The role of adipokines such as resistin, leptin, and adiponectin could be pivotal in the molecular crosstalk between the inflamed intestine and the surrounding mesenteric adipose tissue. Our aims were to a) evaluate their circulating concentrations in patients with active celiac disease (ACD) and compare them to those in patients with diarrhea-predominant irritable bowel syndrome (IBS-d) and healthy subjects; b) establish the impact of genetic variability in resistin; and c) evaluate whether a 1-year gluten-free diet (GFD) modifies circulating concentrations of resistin, leptin, and adiponectin in celiac patients. MATERIAL AND METHODS. The study included 34 ACD patients, 29 IBS-d patients, and 27 healthy controls. Circulating concentrations of resistin, leptin, adiponectin, IL-6, and IL-8 were evaluated at the time of enrollment. Resistin +299 G/A polymorphism was also analysed. In CD patients, biochemical measurements were repeated after a 1-year GFD. RESULTS. Along with higher IL-6 and IL-8 plasma levels, higher resistin and adiponectin concentrations were found in ACD and IBS-d patients compared with controls (p: 0.0351 and p: 0.0020, respectively). Resistin values proved to be predictable from a linear combination of IL-8 and +299 polymorphism. GFD affected resistin (p: 0.0009), but not leptin and adiponectin concentrations. CONCLUSIONS. Our data suggest that these adipokines are involved in modulating inflammatory processes in both CD and IBS-d patients. Alterations in the adipokine profile as well as the higher prevalence of the resistin +299 G/A SNP A allele compared to controls support the hypothesis that, at least in well-defined cases of IBS, a genetic component may also be supposed. PMID:24164320

  6. Human resistin promotes neutrophil proinflammatory activation and neutrophil extracellular trap formation and increases severity of acute lung injury.

    PubMed

    Jiang, Shaoning; Park, Dae Won; Tadie, Jean-Marc; Gregoire, Murielle; Deshane, Jessy; Pittet, Jean Francois; Abraham, Edward; Zmijewski, Jaroslaw W

    2014-05-15

    Although resistin was recently found to modulate insulin resistance in preclinical models of type II diabetes and obesity, recent studies also suggested that resistin has proinflammatory properties. We examined whether the human-specific variant of resistin affects neutrophil activation and the severity of LPS-induced acute lung injury. Because human and mouse resistin have distinct patterns of tissue distribution, experiments were performed using humanized resistin mice that exclusively express human resistin (hRTN(+/-)(/-)) but are deficient in mouse resistin. Enhanced production of TNF-α or MIP-2 was found in LPS-treated hRtn(+/-/-) neutrophils compared with control Rtn(-/-/-) neutrophils. Expression of human resistin inhibited the activation of AMP-activated protein kinase, a major sensor and regulator of cellular bioenergetics that also is implicated in inhibiting inflammatory activity of neutrophils and macrophages. In addition to the ability of resistin to sensitize neutrophils to LPS stimulation, human resistin enhanced neutrophil extracellular trap formation. In LPS-induced acute lung injury, humanized resistin mice demonstrated enhanced production of proinflammatory cytokines, more severe pulmonary edema, increased neutrophil extracellular trap formation, and elevated concentration of the alarmins HMGB1 and histone 3 in the lungs. Our results suggest that human resistin may play an important contributory role in enhancing TLR4-induced inflammatory responses, and it may be a target for future therapies aimed at reducing the severity of acute lung injury and other inflammatory situations in which neutrophils play a major role. PMID:24719460

  7. Leptin and Hunger Levels in Young Healthy Adults After One Night of Sleep Loss

    PubMed Central

    Pejovic, Slobodanka; Vgontzas, Alexandros N.; Basta, Maria; Tsaoussoglou, Marina; Zoumakis, Emanuel; Vgontzas, Angeliki; Bixler, Edward O.; Chrousos, George P.

    2013-01-01

    Summary Short-term sleep curtailment associated with activation of the stress system in healthy, young adults has been shown to be associated with decreased leptin levels, impaired insulin sensitivity and increased hunger and appetite. To assess the effects of one night of sleep loss in a less stressful environment on hunger, leptin, adiponectin, cortisol, and blood pressure/heart rate and whether a 2-hour mid-afternoon nap reverses the changes associated with sleep loss, 21 young healthy individuals (10 men, 11 women) participated in a 7-day sleep deprivation experiment (4 consecutive nights followed by a night of sleep loss and 2 recovery nights). Half of the subjects were randomly assigned to take a mid-afternoon nap (1400–1600) the day following the night of total sleep loss. Serial 24-hour blood sampling and hunger scales were completed on the fourth (pre-deprivation) and sixth day (post-deprivation). Leptin levels were significantly increased after one night of total sleep loss, whereas adiponectin, cortisol levels, blood pressure/heart rate, and hunger were not affected. Daytime napping did not influence the effects of sleep loss on leptin, adiponectin or hunger. Acute sleep loss, in a less stressful environment, influences leptin levels in an opposite manner from that of short-term sleep curtailment associated with activation of the stress system. It appears that sleep loss associated with activation of the stress system but not sleep loss per se may lead to increased hunger and appetite and hormonal changes which ultimately may lead to increased consumption of “comfort” food and obesity. PMID:20545838

  8. Role of adiponectin on antioxidant profile: evaluation during healthy and hypertensive disorders of pregnancy.

    PubMed

    Eleuterio, Níbia Mariana; Palei, Ana C T; Machado, Jackeline S Rangel; Tanus-Santos, Jose E; Cavalli, Ricardo C; Sandrim, Valeria C

    2016-08-01

    The study of adipokines and oxidative stress has aided in understanding pre-eclampsia physiopathology. Therefore, our group aimed to evaluate the correlation between the adipokines (adiponectin and leptin) and the oxidative stress marker malondialdehyde-thiobarbituric acid reactive substances (MDA-TBARS) and antioxidant activity of plasma [ferric reducing ability of plasma (FRAP)] in healthy pregnant women and patients with gestational hypertension and pre-eclampsia. We found a significant negative correlation between MDA-TBARS and adiponectin (r = -0.40, p = 0.0042), suggesting a relationship between antioxidant levels and this adipokine in healthy pregnancies which is altered in patients with gestational hypertension or pre-eclampsia. PMID:26935256

  9. Resistin Induces Hypertension and Insulin Resistance in Mice via a TLR4-Dependent Pathway.

    PubMed

    Jiang, Yun; Lu, Linfang; Hu, Youtao; Li, Qiang; An, Chaoqiang; Yu, Xiaolan; Shu, Le; Chen, Ao; Niu, Congcong; Zhou, Lei; Yang, Zaiqing

    2016-01-01

    Resistin, an adipokine involved in insulin resistance (IR) and diabetes, has recently been reported to play a role in cardiovascular events. However, its effect on blood pressure (BP) and the underlying mechanisms remain unclear. In the present study, we showed that resistin induces hypertension and IR in wild type (WT) mice, but not in tlr4(-/-) mice. Resistin upregulated angiotensinogen (Agt) expression in WT mice, whereas it had no effect on tlr4(-/-) mice, or in mice treated with the angiotensin-converting enzyme inhibitor perindopril. Real-time PCR and chromatin immunoprecipitation further confirmed that resistin activates the renin-angiotensin system (RAS) via the TLR4/P65/Agt pathway. This finding suggested an essential role of resistin in linking IR and hypertension, which may offer a novel target in clinic on the study of the association between diabetes and hypertension. PMID:26917360

  10. Resistin Induces Hypertension and Insulin Resistance in Mice via a TLR4-Dependent Pathway

    PubMed Central

    Jiang, Yun; Lu, Linfang; Hu, Youtao; Li, Qiang; An, Chaoqiang; Yu, Xiaolan; Shu, Le; Chen, Ao; Niu, Congcong; Zhou, Lei; Yang, Zaiqing

    2016-01-01

    Resistin, an adipokine involved in insulin resistance (IR) and diabetes, has recently been reported to play a role in cardiovascular events. However, its effect on blood pressure (BP) and the underlying mechanisms remain unclear. In the present study, we showed that resistin induces hypertension and IR in wild type (WT) mice, but not in tlr4−/− mice. Resistin upregulated angiotensinogen (Agt) expression in WT mice, whereas it had no effect on tlr4−/− mice, or in mice treated with the angiotensin-converting enzyme inhibitor perindopril. Real-time PCR and chromatin immunoprecipitation further confirmed that resistin activates the renin-angiotensin system (RAS) via the TLR4/P65/Agt pathway. This finding suggested an essential role of resistin in linking IR and hypertension, which may offer a novel target in clinic on the study of the association between diabetes and hypertension. PMID:26917360

  11. Resistin deficiency in mice has no effect on pulmonary responses induced by acute ozone exposure.

    PubMed

    Razvi, Shehla S; Richards, Jeremy B; Malik, Farhan; Cromar, Kevin R; Price, Roger E; Bell, Cynthia S; Weng, Tingting; Atkins, Constance L; Spencer, Chantal Y; Cockerill, Katherine J; Alexander, Amy L; Blackburn, Michael R; Alcorn, Joseph L; Haque, Ikram U; Johnston, Richard A

    2015-11-15

    Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines-including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1β)-promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1β, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin; yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indexes of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1α, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient compared with wild-type mice, no genotype-related differences in the other indexes existed following O3 exposure. O3 caused AHR to acetyl-β-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were nonexistent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology. PMID:26386120

  12. Comparative Analysis of GCF Resistin Levels in Obese Subjects with and without Periodontal Disease

    PubMed Central

    Mahendra, Jaideep; Singh, Gurdeep; Pradeep, AR; Sundaravikram; Sekar, Himanshu

    2016-01-01

    Introduction Resistin is an adipocyte derived hormone that has been shown to play a substantial role in the development of insulin resistance. Resistin acts as a pro-inflammatory molecule and stimulates the synthesis and secretion of pro-inflammatory cytokines. Recent studies have reported the association of Gingival Crevicular Fluid (GCF) resistin levels with periodontal condition. Aim The aim of this study was to assess and compare the GCF resistin levels in obese subjects with periodontal health and disease and to correlate the disease severity with GCF resistin levels. Materials and Methods Ninety subjects of both the sexes with age between 20–45 years were selected for the study and were categorized into four groups: 25 obese or overweight subjects with generalized chronic periodontitis (Group-I), 25 obese or overweight subjects with healthy periodontium (Group-II), 25 non-obese subjects with generalized chronic periodontitis (Group-III) and 15 non obese subjects with healthy periodontium (Group-IV). The demographic variables like age, Body Mass Index (BMI), Waist Circumference (WC) were recorded and the clinical periodontal parameters such as Plaque Index (PI), Gingival Index (GI), and Clinical Attachment Level (CAL) were also assessed in all the groups. GCF was collected and assessed for resistin levels. Results The mean GCF resistin levels in Groups I, II, III & IV were 15.14, 9.06, 12.74 and 5.41 ng/dl respectively and the difference in mean GCF resistin level was statistically significant with the p-value<0.001. The mean GCF resistin levels in Group-I was higher compared to Group II and III and the differences in mean GCF resistin levels were statistically significant. GCF resistin levels were positively correlated with BMI, WC and CAL in Group I and CAL correlated with GCF resistin in Group III and this correlation was statistically significant. Conclusion From our study we report that obese subjects with periodontitis have more GCF resistin levels

  13. Sp1 mediates repression of the resistin gene by PPAR{gamma} agonists in 3T3-L1 adipocytes

    SciTech Connect

    Chung, S.S.; Choi, H.H.; Cho, Y.M.; Lee, H.K.; Park, K.S. . E-mail: kspark@snu.ac.kr

    2006-09-15

    Resistin is an adipokine related to obesity and insulin resistance. Expression of the resistin gene is repressed by the treatment of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) agonists, thiazolidinediones (TZDs). In this study, we investigated the mechanism by which TZDs inhibit the resistin gene expression. Resistin gene expression was decreased by TZD in fully differentiated 3T3-L1 adipocytes, which was abolished after treatment of cycloheximide (a protein synthesis inhibitor). TZD could not repress the expression of the resistin gene in the presence of mithramycin A (an Sp1 binding inhibitor). Sp1 binding site of the resistin promoter (-122/-114 bp) was necessary for the repression. Further investigation of the effect of TZDs on the modification of Sp1 showed that the level of O-glycosylation of Sp1 was decreased in this process. These results suggest that PPAR{gamma} activation represses the expression of the resistin gene by modulating Sp1 activity.

  14. A monoclonal antibody against leptin.

    PubMed

    Mahmoudian, Jafar; Jeddi-Tehrani, Mahmood; Bayat, Ali Ahmad; Mahmoudi, Ahmad Reza; Vojgani, Yasaman; Tavangar, Banafsheh; Hadavi, Reza; Zarei, Saeed

    2012-10-01

    Leptin is an important protein that regulates energy storage and homeostasis in humans and animals. Leptin deficiency results in various abnormalities such as diabetes, obesity, and infertility. Producing a high affinity monoclonal antibody against human leptin provides an important tool to monitor and trace leptin function in different biological fluids. In this study, recombinant human leptin was conjugated to KLH and injected into mice. After immunization, mouse myeloma SP2/0 cells were fused with murine splenocytes followed by selection of antibody-producing hybridoma cells. After screening of different hybridoma colonies by ELISA, a high affinity antibody was selected and purified by affinity chromatography. The affinity constant of the antibody was measured by ELISA. Western blot, immunocytochemistry, and flow cytometry experiments were used to characterize the antibody. The anti-leptin antibody had a high affinity (around 1.13 × 10(-9) M) for its antigen. The saturation of the antibody with leptin (20 moles leptin per 1 mole antibody) in Western blot analysis proved that the antibody had specific binding to its antigen. Immunocytochemistry and flow cytometry on JEG-3 (human placental choriocarcinoma cell) cells revealed that the anti-leptin antibody recognized intracellular leptin. In conclusion, we report here the production and characterization of a murine anti-leptin antibody with high affinity for human leptin. PMID:23098305

  15. Deregulation of adipokines related to target organ damage on resistant hypertension.

    PubMed

    Sabbatini, A R; Faria, A P; Barbaro, N R; Gordo, W M; Modolo, R G P; Pinho, C; Fontana, V; Moreno, H

    2014-06-01

    Resistant hypertension (RHTN) includes patients with controlled blood pressure (BP) (CRHTN) and uncontrolled BP (UCRHTN). In fact, RHTN patients are more likely to have target organ damage (TOD), and resistin, leptin and adiponectin may affect BP control in these subjects. We assessed the relationship between adipokines levels and arterial stiffness, left ventricular hypertrophy (LVH) and microalbuminuria (MA). This cross-sectional study included CRHTN (n=51) and UCRHTN (n=38) patients for evaluating body mass index, ambulatory blood pressure monitoring, plasma adiponectin, leptin and resistin concentrations, pulse wave velocity (PWV), MA and echocardiography. Leptin and resistin levels were higher in UCRHTN, whereas adiponectin levels were lower in this same subgroup. Similarly, arterial stiffness, LVH and MA were higher in UCRHTN subgroup. Adiponectin levels negatively correlated with PWV (r=-0.42, P<0.01), and MA (r=-0.48, P<0.01) only in UCRHTN. Leptin was positively correlated with PWV (r=0.37, P=0.02) in UCRHTN subgroup, whereas resistin was not correlated with TOD in both subgroups. Adiponectin is associated with arterial stiffness and renal injury in UCRHTN patients, whereas leptin is associated with arterial stiffness in the same subgroup. Taken together, our results showed that those adipokines may contribute to vascular and renal damage in UCRHTN patients. PMID:24284384

  16. Adipocyte iron regulates adiponectin and insulin sensitivity

    PubMed Central

    Gabrielsen, J. Scott; Gao, Yan; Simcox, Judith A.; Huang, Jingyu; Thorup, David; Jones, Deborah; Cooksey, Robert C.; Gabrielsen, David; Adams, Ted D.; Hunt, Steven C.; Hopkins, Paul N.; Cefalu, William T.; McClain, Donald A.

    2012-01-01

    Iron overload is associated with increased diabetes risk. We therefore investigated the effect of iron on adiponectin, an insulin-sensitizing adipokine that is decreased in diabetic patients. In humans, normal-range serum ferritin levels were inversely associated with adiponectin, independent of inflammation. Ferritin was increased and adiponectin was decreased in type 2 diabetic and in obese diabetic subjects compared with those in equally obese individuals without metabolic syndrome. Mice fed a high-iron diet and cultured adipocytes treated with iron exhibited decreased adiponectin mRNA and protein. We found that iron negatively regulated adiponectin transcription via FOXO1-mediated repression. Further, loss of the adipocyte iron export channel, ferroportin, in mice resulted in adipocyte iron loading, decreased adiponectin, and insulin resistance. Conversely, organismal iron overload and increased adipocyte ferroportin expression because of hemochromatosis are associated with decreased adipocyte iron, increased adiponectin, improved glucose tolerance, and increased insulin sensitivity. Phlebotomy of humans with impaired glucose tolerance and ferritin values in the highest quartile of normal increased adiponectin and improved glucose tolerance. These findings demonstrate a causal role for iron as a risk factor for metabolic syndrome and a role for adipocytes in modulating metabolism through adiponectin in response to iron stores. PMID:22996660

  17. Adipocyte and leptin accumulation in tumor-induced thymic involution.

    PubMed

    Lamas, Alejandro; Lopez, Elena; Carrio, Roberto; Lopez, Diana M

    2016-01-01

    Cell-mediated immunity is an important defense mechanism against pathogens and developing tumor cells. The thymus is the main lymphoid organ involved in the formation of the cell-mediated immune response by the maturation and differentiation of lymphocytes that travel from the bone marrow, through the lymphatic ducts, to become T lymphocytes. Thymic involution has been associated with aging; however, other factors such as obesity, viral infection and tumor development have been shown to increase the rate of shrinkage of this organ. The heavy infiltration of adipocyte fat cells has been reported in the involuted thymuses of aged mice. In the present study, the possible accumulation of such cells in the thymus during tumorigenesis was examined by immunohistochemistry. A significant number of adipocytes around and infiltrating the thymuses of tumor-bearing mice was observed. Leptin is a pro-inflammatory adipocytokine that enhances thymopoiesis and modulates T cell immune responses. The levels of leptin and adiponectin, another adipocytokine that has anti-inflammatory properties, were examined by western blot analysis. While no changes were observed in the amounts of adiponectin present in the thymuses of the normal and tumor-bearing mice, significantly higher levels of leptin were detected in the thymocytes of the tumor-bearing mice. This correlated with an increase in the expression of certain cytokines, such as interleukin (IL)-2, interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF). The co-culture of thymocytes isolated from normal mice with ex vivo isolated adipocytes from tumor-bearing mice yielded similar results. Our findings suggest that the infiltration and accumulation of adipocytes in the thymuses of tumor-bearing mice play an important role in their altered morphology and functions. PMID:26530443

  18. Resistin impairs SIRT1 function and induces senescence-associated phenotype in hepatocytes.

    PubMed

    Yu, An; Zheng, Yu; Zhang, Rongrong; Huang, Jianfeng; Zhu, Zhoujie; Zhou, Ronghua; Jin, Dan; Yang, Zaiqing

    2013-09-01

    Resistin is a cysteine-rich secreted protein which significantly inhibits phosphorylation of AMP-activated protein kinase in both human and mouse hepatocytes. It has been demonstrated that resistin plays an important role in inducing hepatic insulin resistance. However, whether resistin has other unknown influences on hepatocytes still remains poorly studied. Here, we show that recombinant resistin protein significantly reduces expression of SIRT1, attenuates the interaction between SIRT1 and PPARα as well as PGC-1α, and increases PGC-1α acetyl-lysine levels in HepG2 cells. In line with this, resistin treatment weakens the association between SIRT1 and major satellite repeats and alters the transcription level of SIRT1 target genes in mouse primary hepatocytes. Resistin treatment also significantly increases senescence-associated β-galactosidase activity in mouse primary hepatocytes and this effect can be eliminated by co-treatment with the SIRT1 agonists resveratrol and nicotinamide mononucleotide. Our findings suggest that resistin is a negative regulator of SIRT1 in both human hepatoma cell line HepG2 and mouse hepatocytes and that it might also play an important role in the development of senescence-associated liver diseases. PMID:23827175

  19. Association between serum resistin level and outcomes in kidney transplant recipients.

    PubMed

    Nagy, Kristof; Ujszaszi, Akos; Czira, Maria E; Remport, Adam; Kovesdy, Csaba P; Mathe, Zoltan; Rhee, Connie M; Mucsi, Istvan; Molnar, Miklos Z

    2016-03-01

    Resistin is an adipocytokine that is associated with inflammation, coronary artery disease, and other types of cardiovascular disease among patients with normal kidney function. However, little is known about the association of resistin with outcomes in kidney transplant recipients. We collected socio-demographic and clinical parameters, medical and transplant history, and laboratory data from 988 prevalent kidney transplant recipients enrolled in the Malnutrition-Inflammation in Transplant-Hungary Study (MINIT-HU study). Serum resistin levels were measured at baseline. Associations between serum resistin level and death with a functioning graft over a 6-year follow-up period were examined in unadjusted and adjusted models. The mean±SD age of the study population was 51 ± 13 years, among whom 57% were men and 21% were diabetics. Median serum resistin concentrations were significantly higher in patients who died with a functioning graft as compared to those who did not die during the follow-up period (median [IQR]: 22[15-26] vs. 19[14-22] ng/ml, respectively; P < 0.001). Higher serum resistin level was associated with higher mortality risk in both unadjusted and fully adjusted models: HRs (95% CI): 1.33(1.16-1.54) and 1.21(1.01-1.46), respectively. In prevalent kidney transplant recipients, serum resistin was an independent predictor of death with a functioning graft. PMID:26639524

  20. Serum resistin is associated with the severity of microangiopathies in type 2 diabetes

    SciTech Connect

    Osawa, Haruhiko . E-mail: harosawa@m.ehime-u.ac.jp; Ochi, Masaaki; Kato, Kenichi; Yamauchi, Junko; Nishida, Wataru; Takata, Yasunori; Kawamura, Ryoichi; Onuma, Hiroshi; Takasuka, Tomomi; Shimizu, Ikki; Fujii, Yasuhisa; Ohashi, Jun; Makino, Hideichi

    2007-04-06

    Resistin, secreted from adipocytes, causes insulin resistance and diabetes in rodents. To determine the relation between serum resistin and diabetic microangiopathies in humans, we analyzed 238 Japanese T2DM subjects. Mean serum resistin was higher in subjects with either advanced retinopathy (preproliferative or proliferative) (P = 0.0130), advanced nephropathy (stage III or IV) (P = 0.0151), or neuropathy (P = 0.0013). Simple regression analysis showed that serum resistin was positively correlated with retinopathy stage (P = 0.0212), nephropathy stage (P = 0.0052), and neuropathy (P = 0.0013). Multiple regression analysis adjusted for age, gender, and BMI, revealed that serum resistin was correlated with retinopathy stage (P = 0.0144), nephropathy stage (P = 0.0111), and neuropathy (P = 0.0053). Serum resistin was positively correlated with the number of advanced microangiopathies, independent of age, gender, BMI, and either the duration of T2DM (P = 0.0318) or serum creatinine (P = 0.0092). Therefore, serum resistin was positively correlated with the severity of microangiopathies in T2DM.

  1. Emerging role of adipokines in systemic lupus erythematosus.

    PubMed

    Li, Hong-Miao; Zhang, Tian-Ping; Leng, Rui-Xue; Li, Xiang-Pei; Li, Xiao-Mei; Liu, Hai-Rong; Ye, Dong-Qing; Pan, Hai-Feng

    2016-08-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by multisystem organ involvement and unclear pathogenesis. Several adipokines synthesized in the adipose tissue, including leptin, adiponectin, resistin, and chemerin, have been explored in autoimmune rheumatic diseases, especially SLE, and results suggest that these mediators may be implicated in the pathogenesis of SLE. However, the current results are controversial. In this review, we will briefly discuss the expression and possible pathogenic role of several important adipokines, including leptin, adiponectin, resistin, and chemerin in SLE. PMID:27314594

  2. Aldehyde oxidase 1 is highly abundant in hepatic steatosis and is downregulated by adiponectin and fenofibric acid in hepatocytes in vitro

    SciTech Connect

    Neumeier, Markus; Weigert, Johanna; Schaeffler, Andreas; Weiss, Thomas S.; Schmidl, Christian; Buettner, Roland; Bollheimer, Cornelius; Aslanidis, Charalampos; Schoelmerich, Juergen; Buechler, Christa . E-mail: christa.buechler@klinik.uni-regensburg.de

    2006-11-24

    Adiponectin protects the liver from steatosis caused by obesity or alcohol and therefore the influence of adiponectin on human hepatocytes was analyzed. GeneChip experiments indicated that recombinant adiponectin downregulates aldehyde oxidase 1 (AOX1) expression and this was confirmed by real-time RT-PCR and immunoblot. AOX1 is a xenobiotic metabolizing protein and produces reactive oxygen species (ROS), that promote cell damage and fibrogenesis. Adiponectin and fenofibric acid activate peroxisome proliferator-activated receptor-{alpha} (PPAR-{alpha}) and both suppress AOX1 protein and this is blocked by the PPAR-{alpha} antagonist RU486. Obesity is associated with low adiponectin, reduced hepatic PPAR-{alpha} activity and fatty liver, and AOX1 was found induced in the liver of rats on a high-fat diet when compared to controls. Free fatty acids and leptin, that are elevated in obesity, failed to upregulate AOX1 in vitro. The current data indicate that adiponectin reduces AOX1 by activating PPAR-{alpha} whereas fatty liver disease is associated with elevated hepatic AOX1. High AOX1 may be associated with higher ROS well described to induce fibrogenesis in liver tissue but may also influence drug metabolism and activity.

  3. Monitoring leptin activity using the chicken leptin receptor.

    PubMed

    Hen, Gideon; Yosefi, Sera; Ronin, Ana; Einat, Paz; Rosenblum, Charles I; Denver, Robert J; Friedman-Einat, Miriam

    2008-05-01

    We report on the construction of a leptin bioassay based on the activation of chicken leptin receptor in cultured cells. A human embryonic kidney (HEK)-293 cell line, stably transfected with the full-length cDNA of chicken leptin receptor together with a STAT3-responsive reporter gene specifically responded to recombinant human and Xenopus leptins. The observed higher sensitivity of chicken leptin receptor to the former is in agreement with the degree of sequence similarity among these species (about 60 and 38% identical amino acids between humans and chickens, and between humans and Xenopus respectively). The specific activation of signal transduction through the chicken leptin receptor, shown here for the first time, suggests that the transition of Gln269 (implicated in the Gln-to-Pro Zucker fatty mutation in rats) to Glu in chickens does not impair its activity. Analysis of leptin-like activity in human serum samples of obese and lean subjects coincided well with leptin levels determined by RIA. Serum samples of pre- and post partum cows showed a tight correlation with the degree of adiposity. However, specific activation of the chicken leptin receptor in this assay was not observed with serum samples from broiler or layer chickens (representing fat and lean phenotypes respectively) or with those from turkey. Similar leptin receptor activation profiles were observed with cells transfected with human leptin receptor. Further work is needed to determine whether the lack of leptin-like activity in the chicken serum samples is due to a lack of leptin in this species or simply to a serum level of leptin that is below the detection threshold. PMID:18434362

  4. Leptin and Hormones: Energy Homeostasis.

    PubMed

    Triantafyllou, Georgios A; Paschou, Stavroula A; Mantzoros, Christos S

    2016-09-01

    Leptin, a 167 amino acid adipokine, plays a major role in human energy homeostasis. Its actions are mediated through binding to leptin receptor and activating JAK-STAT3 signal transduction pathway. It is expressed mainly in adipocytes, and its circulating levels reflect the body's energy stores in adipose tissue. Recombinant methionyl human leptin has been FDA approved for patients with generalized non-HIV lipodystrophy and for compassionate use in subjects with congenital leptin deficiency. The purpose of this review is to outline the role of leptin in energy homeostasis, as well as its interaction with other hormones. PMID:27519135

  5. Effects of resistin on porcine ovarian follicle steroidogenesis in prepubertal animals: an in vitro study

    PubMed Central

    2013-01-01

    Background Resistin was first reported to be an adipocyte-specific hormone, but recent studies have indicated a connection between resistin and reproductive function. However, it is not yet known if resistin is expressed by the ovary and if it can affect steroidogenesis in ovarian follicles from prepubertal pigs. Methods In this study, using real time PCR, immunoblotting, and ELISA, we quantified resistin expression and concentration in maturing ovarian follicles (small, 3–4 mm; medium, 4–5 mm; large, 6–7 mm) collected from prepubertal pigs. In addition, the dose-responsive effects of recombinant human resistin (0.1, 1, 10, and 100 ng/ml) on steroid hormone (i.e., progesterone [P4], androstendione [A4], testosterone [T], and estradiol [E2]) secretion in culture medium and steroidogenic enzyme (i.e., CYP11A1, 3betaHSD, CYP17A1, 17betaHSD, and CYP19A1) expression in ovarian follicles were determined. Results We observed that resistin gene and protein expression increased significantly (P < 0.05) during follicular growth, with large follicles expressing the highest level of this adipokine. Recombinant resistin also increased P4, A4, and T secretion by up-regulating the steady state levels of CYP11A1, 3betaHSD, CYP17A1, and 17betaHSD. Recombinant resistin had no effects on E2 secretion and CYP19A1 expression in ovarian follicles. Conclusion Our results show resistin expression in ovarian follicles from prepubertal pigs for the first time. We also show that recombinant resistin stimulates steroidogenesis in ovarian follicles by increasing the expression of CYP11A1, 3betaHSD, CYP17A1, and 17betaHSD. The presence of resistin in the porcine ovary and its direct effects on steroidogenesis suggest that resistin is a new regulator of ovary function in prepubertal animals. PMID:23680257

  6. Leptin: a potential novel antidepressant.

    PubMed

    Lu, Xin-Yun; Kim, Chung Sub; Frazer, Alan; Zhang, Wei

    2006-01-31

    Leptin, a hormone secreted from adipose tissue, was originally discovered to regulate body weight. The localization of the leptin receptor in limbic structures suggests a potential role for leptin in emotional processes. Here, we show that rats exposed to chronic unpredictable stress and chronic social defeat exhibit low leptin levels in plasma. Systemic leptin treatment reversed the hedonic-like deficit induced by chronic unpredictable stress and improved behavioral despair dose-dependently in the forced swim test (FST), a model widely used for screening potential antidepressant efficacy. The behavioral effects of leptin in the FST were accompanied by increased neuronal activation in limbic structures, particularly in the hippocampus. Intrahippocampal infusion of leptin produced a similar antidepressant-like effect in the FST as its systemic administration. By contrast, infusion of leptin into the hypothalamus decreased body weight but had no effect on FST behavior. These findings suggest that: (i) impaired leptin production and secretion may contribute to chronic stress-induced depression-like phenotypes, (ii) the hippocampus is a brain site mediating leptin's antidepressant-like activity, and (iii) elevating leptin signaling in brain may represent a novel approach for the treatment of depressive disorders. PMID:16423896

  7. Leptin: A potential novel antidepressant

    PubMed Central

    Lu, Xin-Yun; Kim, Chung Sub; Frazer, Alan; Zhang, Wei

    2006-01-01

    Leptin, a hormone secreted from adipose tissue, was originally discovered to regulate body weight. The localization of the leptin receptor in limbic structures suggests a potential role for leptin in emotional processes. Here, we show that rats exposed to chronic unpredictable stress and chronic social defeat exhibit low leptin levels in plasma. Systemic leptin treatment reversed the hedonic-like deficit induced by chronic unpredictable stress and improved behavioral despair dose-dependently in the forced swim test (FST), a model widely used for screening potential antidepressant efficacy. The behavioral effects of leptin in the FST were accompanied by increased neuronal activation in limbic structures, particularly in the hippocampus. Intrahippocampal infusion of leptin produced a similar antidepressant-like effect in the FST as its systemic administration. By contrast, infusion of leptin into the hypothalamus decreased body weight but had no effect on FST behavior. These findings suggest that: (i) impaired leptin production and secretion may contribute to chronic stress-induced depression-like phenotypes, (ii) the hippocampus is a brain site mediating leptin's antidepressant-like activity, and (iii) elevating leptin signaling in brain may represent a novel approach for the treatment of depressive disorders. PMID:16423896

  8. Drug targeting of leptin resistance.

    PubMed

    Santoro, Anna; Mattace Raso, Giuseppina; Meli, Rosaria

    2015-11-01

    Leptin regulates glucose, lipid and energy homeostasis as well as feeding behavior, serving as a bridge between peripheral metabolically active tissues and the central nervous system (CNS). Indeed, this adipocyte-derived hormone, whose circulating levels mirror fat mass, not only exerts its anti-obesity effects mainly modulating the activity of specific hypothalamic neurons expressing the long form of the leptin receptor (Ob-Rb), but it also shows pleiotropic functions due to the activation of Ob-Rb in peripheral tissues. Nevertheless, several mechanisms have been suggested to mediate leptin resistance, including obesity-associated hyperleptinemia, impairment of leptin access to CNS and the reduction in Ob-Rb signal transduction effectiveness, among others. During the onset and progression of obesity, the dampening of leptin sensitivity often occurs, preventing the efficacy of leptin replacement therapy from overcoming obesity and/or its comorbidities. This review focuses on obesity-associated leptin resistance and the mechanisms underpinning this condition, to highlight the relevance of leptin sensitivity restoration as a useful therapeutic strategy to treat common obesity and its complications. Interestingly, although promising strategies to counteract leptin resistance have been proposed, these pharmacological approaches have shown limited efficacy or even relevant adverse effects in preclinical and clinical studies. Therefore, the numerous findings from this review clearly indicate a lack of a single and efficacious treatment for leptin resistance, highlighting the necessity to find new therapeutic tools to improve leptin sensitivity, especially in patients with most severe disease profiles. PMID:26071010

  9. Resistin reinforces interferon λ-3 to eliminate hepatitis C virus with fine-tuning from RETN single-nucleotide polymorphisms

    PubMed Central

    Chang, Ming-Ling; Liang, Kung-Hao; Ku, Cheng-Lung; Lo, Chia-Chi; Cheng, Ya-Ting; Hsu, Chen-Ming; Yeh, Chau-Ting; Chiu, Cheng-Tang

    2016-01-01

    The effect of resistin (RETN) on the response to anti-HCV therapy remains unclear. A prospective cohort study was performed using 655 consecutive HCV patients, of whom 513 had completed a course of interferon-based therapy. Multivariate and GEE analyses revealed four RETN single-nucleotide polymorphisms (SNPs), rs34861192, rs3219175, rs3745367 and rs1423096, to be synergistically associated with resistin levels. After adjusting for co-factors such as interferon λ-3 (IFNL3)-rs12979860, the resistin level and the hyper-resistinemic genotype at the 4 RETN SNPs were positively and negatively associated with a sustained virological response (SVR), respectively. RETN-rs3745367 was in linkage disequilibrium with IFNL3-rs12979860. Compared to non-SVR patients, SVR patients had higher levels of pre-therapy resistin, primarily originating from intrahepatic lymphocytes, stellate cells, Kupffer cells, hepatic progenitor cells and hepatocytes. This difference diminished over the course of therapy, as only SVR patients exhibited a 24-week post-therapy decrease in resistin. Both resistin and IFNL3 mRNAs were upregulated, but only resistin mRNA was upregulated by recombinant resistin in peripheral blood mononuclear cells with and without hyper-resistinemic genotypes of the 4 RETN SNPs, respectively. Fine-tuned by RETN SNPs, intrahepatic, multi-cellular resistin reinforced IFNL3 in eliminating HCV via immunomodulation to counteract pro-inflammation. These results encourage the development of novel resistin-targeted anti-viral agents. PMID:27477870

  10. Leptin in Alzheimer's disease.

    PubMed

    Magalhães, C A; Carvalho, M G; Sousa, L P; Caramelli, P; Gomes, K B

    2015-10-23

    Alzheimer's disease (AD) is the most common cause of progressive dementia in the elderly population. AD is histologically characterized by accumulation of amyloid-β protein (Aβ) on extracellular plaques and deposition of hyperphosphorylated tau protein in intracellular neurofibrillary tangles. Several studies have shown that obesity may precede dementia and that lifestyle factors play a critical role in the onset of AD. Furthermore, accumulating evidence indicates that obesity is an independent risk factor for developing AD. In this scenario, the understanding of the role of adipose tissue in brain health is essential to clarify the establishment of demential processes. The objective of this work was to review studies regarding leptin, an anorexigenic peptide hormone synthesized in adipocytes, in the context of dementia. Some authors proposed that leptin evaluation might be a better predictor of dementia than traditional anthropometric measures. Leptin, once established as a biomarker, could enhance the understanding of late-onset AD risk over the life course, as well as the clinical progression of prodromal state to manifested AD. Other studies have proposed that leptin presents neuroprotective activities, which could be explained by inhibiting the amyloidogenic process, reducing the levels of tau protein phosphorylation and improving the cognitive function. PMID:26279362

  11. Leptin and reproductive function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adipose tissue plays a dynamic role in whole-body homeostasis by acting as an endocrine organ. Collective evidence indicates a strong link between neural influences and adipocyte expression and secretion of leptin. Developmental changes in these relationships are considered important for pubertal ...

  12. Long-Lived αMUPA Mice Show Attenuation of Cardiac Aging and Leptin-Dependent Cardioprotection

    PubMed Central

    Levy, Esther; Kornowski, Ran; Gavrieli, Reut; Fratty, Ilana; Greenberg, Gabriel; Waldman, Maayan; Birk, Einat; Shainberg, Asher; Akirov, Amit; Miskin, Ruth; Hochhauser, Edith

    2015-01-01

    αMUPA transgenic mice spontaneously consume less food compared with their wild type (WT) ancestors due to endogenously increased levels of the satiety hormone leptin. αMUPA mice share many benefits with mice under caloric restriction (CR) including an extended life span. To understand mechanisms linked to cardiac aging, we explored the response of αMUPA hearts to ischemic conditions at the age of 6, 18, or 24 months. Mice were subjected to myocardial infarction (MI) in vivo and to ischemia/reperfusion ex vivo. Compared to WT mice, αMUPA showed functional and histological advantages under all experimental conditions. At 24 months, none of the WT mice survived the first ischemic day while αMUPA mice demonstrated 50% survival after 7 ischemic days. Leptin, an adipokine decreasing under CR, was consistently ~60% higher in αMUPA sera at baseline. Leptin levels gradually increased in both genotypes 24h post MI but were doubled in αMUPA. Pretreatment with leptin neutralizing antibodies or with inhibitors of leptin signaling (AG-490 and Wortmannin) abrogated the αMUPA benefits. The antibodies also reduced phosphorylation of the leptin signaling components STAT3 and AKT specifically in the αMUPA myocardium. αMUPA mice did not show elevation in adiponectin, an adipokine previously implicated in CR-induced cardioprotection. WT mice treated for short-term CR exhibited cardioprotection similar to that of αMUPA, however, along with increased adiponectin at baseline. Collectively, the results demonstrate a life-long increased ischemic tolerance in αMUPA mice, indicating the attenuation of cardiac aging. αMUPA cardioprotection is mediated through endogenous leptin, suggesting a protective pathway distinct from that elicited under CR. PMID:26673217

  13. Effects of high levels of glucose on the steroidogenesis and the expression of adiponectin receptors in rat ovarian cells

    PubMed Central

    Chabrolle, Christine; JeanPierre, Eric; Tosca, Lucie; Ramé, Christelle; Dupont, Joëlle

    2008-01-01

    Background Reproductive dysfunction in the diabetic female rat is associated with altered folliculogenesis and steroidogenesis. However, the molecular mechanisms involved in the reduction of steroid production have not been described. Adiponectin is an adipocytokine that has insulin-sensitizing actions including stimulation of glucose uptake in muscle and suppression of glucose production in liver. Adiponectin acts via two receptor isoforms – AdipoR1 and AdipoR2 – that are regulated by hyperglycaemia and hyperinsulinaemia in liver and muscle. We have recently identified AdipoR1 and AdipoR2 in rat ovary. However, their regulation in ovaries of diabetic female rat remains to be elucidated. Methods We incubated rat primary granulosa cells in vitro with high concentrations of glucose (5 or 10 g/l) + or - FSH (10-8 M) or IGF-1 (10-8 M), and we studied the ovaries of streptozotocin-induced diabetic rats (STZ) in vivo. The levels of oestradiol and progesterone in culture medium and serum were measured by RIA. We used immunoblotting to assay key steroidogenesis factors (3beta HSD, p450scc, p450 aromatase, StAR), and adiponectin receptors and various elements of signalling pathways (MAPK ERK1/2 and AMPK) in vivo and in vitro. We also determined cell proliferation by [3H] thymidine incorporation. Results Glucose (5 or 10 g/l) impaired the in vitro production in rat granulosa cells of both progesterone and oestradiol in the basal state and in response to FSH and IGF-1 without affecting cell proliferation and viability. This was associated with substantial reductions in the amounts of 3beta HSD, p450scc, p450 aromatase and StAR proteins and MAPK ERK1/2 phosphorylation. In contrast, glucose did not affect the abundance of AdipoR1 or AdipoR2 proteins. In vivo, as expected, STZ treatment of rats caused hyperglycaemia and insulin, adiponectin and resistin deficiencies. Plasma progesterone and oestradiol levels were also reduced in STZ rats. However, the amounts of 3beta HSD

  14. 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

  15. Leptin and its receptors.

    PubMed

    Wada, Nobuhiro; Hirako, Satoshi; Takenoya, Fumiko; Kageyama, Haruaki; Okabe, Mai; Shioda, Seiji

    2014-11-01

    Leptin is mainly produced in the white adipose tissue before being secreted into the blood and transported across the blood-brain barrier. Leptin binds to a specific receptor (LepR) that has numerous subtypes (LepRa, LepRb, LepRc, LepRd, LepRe, and LepRf). LepRb, in particular, is expressed in several brain nuclei, including the arcuate nucleus, the paraventricular nucleus, and the dorsomedial, lateral and ventromedial regions of the hypothalamus. LepRb is also co-expressed with several neuropeptides, including proopiomelanocortin, neuropeptide Y, galanin, galanin-like peptide, gonadotropin-releasing hormone, tyrosine hydroxylase and neuropeptide W. Functionally, LepRb induces activation of the JAK2/ERK, /STAT3, /STAT5 and IRS/PI3 kinase signaling cascades, which are important for the regulation of energy homeostasis and appetite in mammals. In this review, we discuss the structure, genetics and distribution of the leptin receptors, and their role in cell signaling mechanisms. PMID:25218975

  16. Leptin in teleostean fish, towards the origins of leptin physiology.

    PubMed

    Gorissen, Marnix; Flik, Gert

    2014-11-01

    Teleostean leptin was first cloned in 2005, more than a decade after the discovery of mammalian leptin. The reason for this delay lies in the very poor primary sequence conservation (∼13-25%) between mammalian and fish leptins. These low sequence conservations indicate a high degree of molecular evolvability and warrant a search for different and original functions of leptin in teleosts. Indeed, new and original insights are obtained because of the unique phylogenetic position of teleostean fish as the earliest vertebrates and because of their ectothermy, which means that teleosts are more flexible in changing their metabolism than mammals and leptin could play a role in this flexibility. Research during the last decade reveals that leptin is a truly pleiotropic hormone in fish and mammals alike, with functions among others in the regulation of food intake and body weight, development, but also in the regulation of the stress axis and acclimation processes to for instance low oxygen levels in the water. In this review, we provide an overview of the teleostean leptin work done in the last ten years, and demonstrate that the power of a comparative approach leads to new insights on the origins of leptin physiology. PMID:24977940

  17. Effect of oncological treatment on serum adipocytokine levels in patients with stage II–III breast cancer

    PubMed Central

    COSKUN, TEOMAN; KOSOVA, FUNDA; ARI, ZEKI; SAKARYA, ASLAN; KAYA, YAVUZ

    2016-01-01

    Adipose tissue-derived hormones (adipocytokines), such as adiponectin, leptin, resistin and visfatin, and the pancreatic hormone insulin, have been suggested to play a role in carcinogenesis. we therefore hypothesized that the oncological treatment of breast cancer may alter the serum levels of these adipocytokines and insulin. In this study, we aimed to compare the serum levels of adipocytokines and insulin between the pre- and post-treatment period in patients with breast cancer. In this prospective study, 20 consecutive patients with stage II and III breast cancer underwent breast-conserving surgery or total mastectomy and/or axillary dissection. The patients received adjuvant chemotherapy and radiotherapy, if necessary. Blood samples were obtained during the preoperative period and postoperatively after completion of the adjuvant therapy. There was no statistically significant difference between the pre- and post-treatment levels of visfatin, adiponectin and leptin. However, the serum insulin and resistin levels and insulin resistance were found to be statistically significantly increased following treatment (P<0.05). Post-treatment resistin levels were positively correlated with insulin resistance (r=0.45, P<0.05). Therefore, oncological treatment of stage II and III breast cancer did not affect visfatin, adiponectin and leptin levels, but statistically significantly increased resistin levels and insulin resistance. In addition, the post-treatment resistin levels were positively correlated with insulin resistance, suggesting that resistin may be involved in the development of insulin resistance in breast cancer patients following treatment. PMID:27123303

  18. Peripheral Leptin Regulates Bone Formation

    PubMed Central

    Turner, Russell T.; Kalra, Satya P.; Wong, Carmen P.; Philbrick, Kenneth A.; Lindenmaier, Laurence B.; Boghossian, Stephane; Iwaniec, Urszula T.

    2012-01-01

    Substantial evidence does not support the prevailing view that leptin, acting through a hypothalamic relay, decreases bone accrual by inhibiting bone formation. To clarify the mechanisms underlying regulation of bone architecture by leptin, we evaluated bone growth and turnover in wild type (WT) mice, leptin receptor-deficient db/db mice, leptin-deficient ob/ob mice and ob/ob mice treated with leptin. We also performed hypothalamic leptin gene therapy to determine the effect of elevated hypothalamic leptin levels on osteoblasts. Finally, to determine the effects of loss of peripheral leptin signaling on bone formation and energy metabolism, we used bone marrow (BM) from WT or db/db donor mice to reconstitute the hematopoietic and mesenchymal stem cell compartments in lethally irradiated WT recipient mice. Decreases in bone growth, osteoblast-lined bone perimeter and bone formation rate were observed in ob/ob mice and greatly increased in ob/ob mice following subcutaneous administration of leptin. Similarly, hypothalamic leptin gene therapy increased osteoblast-lined bone perimeter in ob/ob mice. In spite of normal osteoclast-lined bone perimeter, db/db mice exhibited a mild but generalized osteopetrotic-like (calcified cartilage encased by bone) skeletal phenotype and greatly reduced serum markers of bone turnover. Tracking studies and histology revealed quantitative replacement of BM cells following BM transplantation. WT mice engrafted with db/db BM did not differ in energy homeostasis from untreated WT mice or WT mice engrafted with WT BM. Bone formation in WT mice engrafted with WT BM did not differ from WT mice, whereas bone formation in WT mice engrafted with db/db cells did not differ from the low rates observed in untreated db/db mice. In summary, our results indicate that leptin, acting primarily through peripheral pathways, increases osteoblast number and activity. PMID:22887758

  19. Leptin Enhances Cholangiocarcinoma Cell Growth

    PubMed Central

    Fava, Giammarco; Alpini, Gianfranco; Rychlicki, Chiara; Saccomanno, Stefania; DeMorrow, Sharon; Trozzi, Luciano; Candelaresi, Cinzia; Venter, Julie; Di Sario, Antonio; Marzioni, Marco; Bearzi, Italo; Glaser, Shannon; Alvaro, Domenico; Marucci, Luca; Francis, Heather; Svegliati-Baroni, Gianluca; Benedetti, Antonio

    2008-01-01

    Cholangiocarcinoma is a strongly aggressive malignancy with a very poor prognosis. Effective therapeutic strategies are lacking because molecular mechanisms regulating cholangiocarcinoma cell growth are unknown. Furthermore, experimental in vivo animal models useful to study the pathophysiologic mechanisms of malignant cholangiocytes are lacking. Leptin, the hormone regulating caloric homeostasis, which is increased in obese patients, stimulates the growth of several cancers, such as hepatocellular carcinoma. The aim of this study was to define if leptin stimulates cholangiocarcinoma growth. We determined the expression of leptin receptors in normal and malignant human cholangiocytes. Effects on intrahepatic cholangiocarcinoma (HuH-28) cell proliferation, migration, and apoptosis of the in vitro exposure to leptin, together with the intracellular pathways, were then studied. Moreover, cholangiocarcinoma was experimentally induced in obese fa/fa Zucker rats, a genetically established animal species with faulty leptin receptors, and in their littermates by chronic feeding with thioacetamide, a potent carcinogen. After 24 weeks, the effect of leptin on cholangiocarcinoma development and growth was assessed. Normal and malignant human cholangiocytes express leptin receptors. Leptin increased the proliferation and the metastatic potential of cholangiocarcinoma cells in vitro through a signal transducers and activators of transcription 3–dependent activation of extracellular signal-regulated kinase 1/2. Leptin increased the growth and migration, and was antiapoptotic for cholangiocarcinoma cells. Moreover, the loss of leptin function reduced the development and the growth of cholangiocarcinoma. The experimental carcinogenesis model induced by thioacetamide administration is a valid and reproducible method to study cholangiocarcinoma pathobiology. Modulation of the leptin-mediated signal could be considered a valid tool for the prevention and treatment of

  20. Leptin: pharmacological aspects in gynecology.

    PubMed

    Sorace, M; Tripodi, L; Tripodi, A; Groppetti, D; Cremonesi, F

    2006-01-01

    Hematic levels of leptin vary in relation to numerous metabolic factors and are able to interact in perfect synchrony with the hormones involved in the hypothalamus-pituitary-ovarian axis during the various phases of the reproductive cycle. In general it is maintained that the complex and multiple action mechanisms of leptin need to be clarified by further in-depth research studies. It is likely that valid pharmacological applications of leptin will be found for human use although it is too premature to talk about concrete pharmacological answers and to formulate the relative complete technical protocols. In medicine the therapeutic use of leptin for humans has been reported in only a few cases. In fact human recombinant leptin has already been administered in gynecology for hypothalamic amenorrhea with precise protocols. In addition, very recent studies have provided the basis for new strategies to be developed concerning the use of leptin to fight multiple sclerosis. At present there are considerable technical and economic problems in the production of leptin on a large scale. Most likely these problems will be overcome in the foreseeable future, and will involve new techniques related to genetics, cellular reprograming, and stem cells. In fact, new pharmacogenetic research has provided encouraging results for the production in industrial quantities of a more effective and fail-proof leptin. Even considering that norms have not yet been proposed for pharmacological interventions with leptin for use directly on humans, in our work we have studied by immunohistochemistry methods the distribution of leptin and its receptor (Ob-R) in the ovaries of the female dog as a biological model, in the pre- and postpubertal phases and in other phases of the ovarian cycle. Given the hypothesis that the information obtained from immunohistochemical localization of the hormone and its receptor in various ovarian structures is transferable to humans, it could be useful to define

  1. Relevance and clinical significance of serum resistin level in obese T2DM rhesus monkey models.

    PubMed

    Qi, S-D; He, Z-L; Chen, Y; Ma, J; Yu, W-H; Li, Y-Y; Yang, F-M; Wang, J-B; Chen, L-X; Zhao, Y; Lu, S-Y

    2015-09-01

    Resistin is a type of hormone-like adipocytokines, which is secreted specifically by adipocytes. It may be a key factor in the development of type 2 diabetes mellitus (T2DM) from obesity- associated insulin resistance due to results that show that it has a close relationship with insulin resistance in rodents. We utilized the rhesus monkeys as study objects to preliminarily test the association with glucose metabolism and to conduct a correlation analysis for clinical parameters and serum resistin levels in obese rhesus monkey models of T2DM. The results suggested that resistin was significantly increased in T2DM monkeys (P <0.01), and that resistin had a positive correlation respectively with total cholesterol (TC), low-density lipoprotein (LDL-C), fasting plasma glucose (FPG), fasting insulin (FPI) and glycated hemoglobin (HbA1c), Insulin resistance index (HOA-IR), but a negative correlation with islet β-cell function (HOMA-β). In the course of glucose metabolism, reverse release change of resistin and insulin in T2DM monkeys occurred, but the phenomenon that was not observed in the control group, these findings indicated that resistin negatively regulated and interfered with carbohydrate metabolism in T2DM monkey models. The character of the releasing change of resistin might be a unique process in T2DM. Therefore, all of the results could provide references for clinical diagnostic criteria for human cases of T2DM, and could have clinical significance for obese T2DM diagnosis and degree of insulin resistance. PMID:26069076

  2. Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

    PubMed

    Jang, Jessica C; Chen, Gang; Wang, Spencer H; Barnes, Mark A; Chung, Josiah I; Camberis, Mali; Le Gros, Graham; Cooper, Philip J; Steel, Cathy; Nutman, Thomas B; Lazar, Mitchell A; Nair, Meera G

    2015-01-01

    Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated

  3. Macrophage-Derived Human Resistin Is Induced in Multiple Helminth Infections and Promotes Inflammatory Monocytes and Increased Parasite Burden

    PubMed Central

    Jang, Jessica C.; Chen, Gang; Wang, Spencer H.; Barnes, Mark A.; Chung, Josiah I.; Camberis, Mali; Le Gros, Graham; Cooper, Philip J.; Steel, Cathy; Nutman, Thomas B.; Lazar, Mitchell A.; Nair, Meera G.

    2015-01-01

    Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg− mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated

  4. Is there a role for leptin in the reduction of depression symptoms during weight loss therapy in obese adolescent girls and boys?

    PubMed

    de Carvalho-Ferreira, Joana Pereira; Masquio, Deborah Cristina Landi; da Silveira Campos, Raquel Munhoz; Dal Molin Netto, Bárbara; Corgosinho, Flavia Campos; Sanches, Priscila L; Tock, Lian; Tufik, Sergio; de Mello, Marco Túlio; Finlayson, Graham; Dâmaso, Ana R

    2015-03-01

    Several studies have sought to clarify the association between adolescent obesity and psychological distress. Recently, a biological link between leptin resistance and depression has been proposed. The aim of the present study was to examine changes in leptin concentrations as a potential predictor of reduced depression symptoms in obese adolescents during long-term interdisciplinary weight loss therapy. Seventy-five obese adolescents (age: 16.28±2.37 years; BMI: 35.65±4.64 kg/m2) engaged in a long-term interdisciplinary therapy for weight loss. They were evaluated at baseline and after 1 year of treatment for body composition, serum analyses and depression symptomatology. After therapy, body mass BMI, fat mass (% and kg), waist circumference, visceral, subcutaneous and visceral/subcutaneous fat and depression symptoms decreased and lean mass (%) increased significantly. There was an improvement in inflammatory profiles with a significant reduction in leptin and increase in adiponectin. Regression analyses showed that decreased leptin predicted amelioration in depression symptoms independent of age, gender and changes in visceral fat, body mass, fat mass (%) and leptin/adiponectin ratio. These associations appear stronger in girls than boys. The attenuation of hyperleptinemia appears to play an important role in the association between weight loss and depression, particularly in obese girls. PMID:25629253

  5. 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

  6. Human resistin stimulates the pro-inflammatory cytokines TNF-{alpha} and IL-12 in macrophages by NF-{kappa}B-dependent pathway

    SciTech Connect

    Silswal, Nirupama; Singh, Anil K.; Aruna, Battu; Mukhopadhyay, Sangita; Ghosh, Sudip; Ehtesham, Nasreen Z. . E-mail: nas_ehtesham@yahoo.com

    2005-09-09

    Resistin, a recently discovered 92 amino acid protein involved in the development of insulin resistance, has been associated with obesity and type 2 diabetes. The elevated serum resistin in human diabetes is often associated with a pro-inflammatory milieu. However, the role of resistin in the development of inflammation is not well understood. Addition of recombinant human resistin protein (hResistin) to macrophages (both murine and human) resulted in enhanced secretion of pro-inflammatory cytokines, TNF-{alpha} and IL-12, similar to that obtained using 5 {mu}g/ml lipopolysaccharide. Both oligomeric and dimeric forms of hResistin were able to activate these cytokines suggesting that the inflammatory action of resistin is independent of its conformation. Heat denatured hResistin abrogated cytokine induction while treatment of recombinant resistin with polymyxin B agarose beads had no effect thereby ruling out the role of endotoxin in the recombinant hResistin mediated cytokine induction. The pro-inflammatory nature of hResistin was further evident from the ability of this protein to induce the nuclear translocation of NF-{kappa}B transcription factor as seen from electrophoretic mobility shift assays. Induction of TNF-{alpha} in U937 cells by hResistin was markedly reduced in the presence of either dominant negative I{kappa}B{alpha} plasmid or PDTC, a pharmacological inhibitor of NF-{kappa}B. A protein involved in conferring insulin resistance is also a pro-inflammatory molecule that has important implications.

  7. 13C metabolic flux analysis shows that resistin impairs the metabolic response to insulin in L6E9 myotubes

    PubMed Central

    2014-01-01

    Background It has been suggested that the adipokine resistin links obesity and insulin resistance, although how resistin acts on muscle metabolism is controversial. We aimed to quantitatively analyse the effects of resistin on the glucose metabolic flux profile and on insulin response in L6E9 myotubes at the metabolic level using a tracer-based metabolomic approach and our in-house developed software, Isodyn. Results Resistin significantly increased glucose uptake and glycolysis, altering pyruvate utilisation by the cell. In the presence of resistin, insulin only slightly increased glucose uptake and glycolysis, and did not alter the flux profile around pyruvate induced by resistin. Resistin prevented the increase in gene expression in pyruvate dehydrogenase-E1 and the sharp decrease in gene expression in cytosolic phosphoenolpyruvate carboxykinase-1 induced by insulin. Conclusions These data suggest that resistin impairs the metabolic activation of insulin. This impairment cannot be explained by the activity of a single enzyme, but instead due to reorganisation of the whole metabolic flux distribution. PMID:25217974

  8. Resistin impairs glucose permeability in EA.hy926 cells by down-regulating GLUT1 expression.

    PubMed

    Li, Qiang; Cai, Yuxi; Huang, Jing; Yu, Xiaolan; Sun, Jun; Yang, Zaiqing; Zhou, Lei

    2016-10-15

    Type 2 diabetes mellitus (T2DM) is a chronic disease which is now affecting the health of more and more people in the world. Resistin, discovered in 2001, is considered to be closely related to metabolic dysfunction and obesity. Previous study showed that hyperglycemia is always accompanied by a high serum resistin concentration. We therefore investigated whether resistin can mediate glucose transfer across the blood-tissue barrier. Here, we employed a transwell system to analyze glucose permeability in EA.hy926 human endothelial cells treated without or with human resistin. In EA.hy926 cells treated with resistin, the permeability to glucose was heavily impaired. This was due to the down-regulation of GLUT1 expression as a result of the treatment, rather than regulation of tight junctions. In addition, overexpression of GLUT1 in EA.hy926 cells was able to recover the blocking effect of resistin on glucose permeability. We further found that resistin could inhibit the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and consequently impede the transcription of GLUT1. The results of the present study suggested that resistin could cause glucose retention in serum and thus result in hyperglycemia. This provides a novel explanation for hyperglycemia and a potential new way of treating type 2 diabetes mellitus. PMID:27353463

  9. C-Reactive Protein Modifies the Association of Plasma Leptin With Coronary Calcium in Asymptomatic Overweight Individuals

    PubMed Central

    Martin, Seth S.; Qasim, Atif N.; Rader, Dan J.; Reilly, Muredach P.

    2014-01-01

    Evidence suggests putative interactions of leptin and C-reactive protein (CRP) in the pathogenesis of adiposity-related atherosclerotic cardiovascular disease (CVD). Therefore, we investigated whether CRP levels modify the relationship of leptin levels with coronary artery calcium (CAC). We examined 1,460 asymptomatic individuals from two community-based cross-sectional studies coordinated at a single, university-based research center. We focused on subjects who were overweight or obese (BMI ≥25) given greater biologic plausibility in this setting. In multivariable CAC models, we analyzed the interaction of log-transformed plasma leptin levels with higher CRP levels as defined by three cut-points: two clinically based (2 mg/l, 3 mg/l) and one dataset specific (sex-specific upper quartile). The association of plasma leptin with CAC was modified by higher CRP regardless of cut-point (interaction term P values all <0.01 in fully adjusted models). Leptin levels were associated with CAC in those with high, but not low CRP levels (e.g., tobit ratio for a 1 unit increase in ln(leptin) (95% CI): 2.18 (1.29–3.66) if CRP level ≥3 mg/l; N = 461 vs. 0.94 (0.67–1.31) if CRP levels <3 mg/l; N = 999) in fully adjusted models. No interaction with CRP was present in control analyses with adiponectin, BMI and waist circumference. In conclusion, in asymptomatic overweight and obese adults, increased leptin levels were independently associated with increased CAC in the presence of high, but not low CRP levels, supporting a leptin-CRP interface in atherosclerosis risk. PMID:21738237

  10. Correlation between Resistin, Tuberculosis and Khat Addiction: A Study from South Western Province of Saudi Arabia

    PubMed Central

    Alvi, Ayesha; Fatima, Nuzhath; Jerah, Ahmed Ali; Rizwan, Mohammed; Hobani, Yahya Hasan; Sunosi, Rashad Al; Taha, Manal Mohamed El Hassan; Habiballah, Eldaw Mohamed; Agarwal, Pradeep Kumar; Abdulwahab, Siddig Ibrahim

    2015-01-01

    Tuberculosis(TB) is a disease of global significance, which accounts for a death in every 15 seconds. Recent studies shows TB is rising in certain parts of the world, and Saudi Arabia is one of them. Several factor contribute in predisposing the subjects for infection including but not limited to addiction to various compounds which have immune modulation properties, such as amphetamines and Heroin etc. Khat a plant whose leaves are chewed for its euphoric effect in east Africa and Arabian Peninsula including Saudi Arabia, is considered as mildly addictive, and its principle compound, Cathinone shares structural and functional similarity with amphetamine a known immunomodulator. Tuberculosis being a disease of immune modulation has a varied spectrum of complex interplay of proinflammatory molecules, resistin is one of them. In the present study, we try to explore the trinity of khat addiction, serum resistin level and tuberculosis by correlating the serum resistin level in non khat addicted healthy subjects, khat addicted healthy subjects, and in patients, both khat addicted and non khat addicted, with active tuberculosis. We observed significantly higher resistin level among the apparently healthy khat addicted subjects as compared to non addicted healthy controls. Thereafter, when we compare the resistin levels between khat addicted and non khat addicted TB patients we did not found significant difference between the two groups. However bacillary load was observe to be significantly higher among the khat addicted TB patient as compare to non addicted one. Validation of above results in animal model revealed dose dependant increase in bacillary growth in the Wistar rats treated with khat. Taken together these results suggest the role of khat in immune modulation albeit in the limited frame of resistin level. PMID:26448186

  11. Association of Resistin with Insulin Resistance and Factors of Metabolic Syndrome in North Indians.

    PubMed

    Singh, Arun Kumar; Tiwari, Sunita; Gupta, Abhishek; Shukla, Kamla Kant; Chhabra, Kumar Gaurav; Pandey, Achileshwar; Pant, Aditya Bhushan

    2015-07-01

    Metabolic syndrome (MetS) is a cluster of interrelated common clinical disorders. The role of resistin in insulin sensitivity and MetS is controversial till date. So, the aim of the present study was to investigate the relationship of plasma resistin levels with markers of the MetS in Indian subjects. In a case control study, total 528 subjects were selected for the study. 265 (194 male and 71 female) were cases (with MetS) and 263 (164 male and 99 female) were controls (without MetS). Required anthropometric measurements and calculations were carried out accordingly. All the Biochemical estimations were carried out according to standard protocol. Resistin level was measured by the standard protocol (By ELISA i.e. enzyme linked immunosorbent assay) as illustrated in the kit. Insulin level was also measured by the standard protocol as illustrated in the kit and insulin resistance was calculated by the standard procedures. Plasma resistin levels were significantly higher in cases compared with controls (male = 13.05 ± 4.31 vs. 7.04 ± 2.09 ng/ml; p ≤ 0.001 and female = 13.53 ± 4.14 vs. 7.42 ± 2.30 ng/ml; p ≤ 0.001). Plasma resistin levels were well correlated with waist circumference, glucose, triglycerides, waist/hip ratio, systolic and diastolic blood pressure, high density lipoprotein, total cholesterol, serum low density lipoprotein, serum very low density lipoprotein, insulin and insulin resistance. Plasma resistin levels were elevated in presence of the MetS and were associated with increased metabolic risk factors. PMID:26089609

  12. Serum Resistin Levels Are Associated with Adiposity and Insulin Sensitivity in Obese Hispanic Subjects

    PubMed Central

    Nieva-Vazquez, Adriana; Torres-Rasgado, Enrique; López-López, José G.; Romero, Jose R.

    2014-01-01

    Abstract Background and Aims: Resistin is involved in the development of obesity and insulin resistance (IR) in mice and may play a similar role in humans through mechanisms that remain unresolved. The objective of this study was to characterize the relationship between resistin levels in obese subjects with and without IR among Hispanic subjects. Material and Methods: A cross-sectional study was performed on 117 nondiabetic Hispanic subjects of both genders that were allocated into three study groups: A control group (n=47) of otherwise healthy individuals in metabolic balance, a group with obesity (OB) (n=36), and a group with obesity and IR (OB-IR) (n=34). Anthropometric and clinical characterization was carried out, and resistin levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: We found that resistin levels were higher in OB and OB-IR groups when compared to the control group (1331.79±142.15 pg/mL, 1266.28±165.97 pg/mL vs. 959.21±171.43 pg/mL; P<0.05), an effect that was not confounded by age (control, 34.04±10.00 years; OB, 37.30±10.78 years; and OB-IR, 35.67±10.15 years). In addition, we observed a significant correlation (P<0.001) between resistin levels and higher adiposity and insulin sensitivity (IS) in our cohort. Conclusions: Our results suggest that higher resistin levels are associated with higher adiposity and lower IS among obese Hispanic subjects. PMID:24266722

  13. Correlation between Resistin, Tuberculosis and Khat Addiction: A Study from South Western Province of Saudi Arabia.

    PubMed

    Alvi, Ayesha; Fatima, Nuzhath; Jerah, Ahmed Ali; Rizwan, Mohammed; Hobani, Yahya Hasan; Sunosi, Rashad Al; Taha, Manal Mohamed El Hassan; Habiballah, Eldaw Mohamed; Agarwal, Pradeep Kumar; Abdulwahab, Siddig Ibrahim

    2015-01-01

    Tuberculosis(TB) is a disease of global significance, which accounts for a death in every 15 seconds. Recent studies shows TB is rising in certain parts of the world, and Saudi Arabia is one of them. Several factor contribute in predisposing the subjects for infection including but not limited to addiction to various compounds which have immune modulation properties, such as amphetamines and Heroin etc. Khat a plant whose leaves are chewed for its euphoric effect in east Africa and Arabian Peninsula including Saudi Arabia, is considered as mildly addictive, and its principle compound, Cathinone shares structural and functional similarity with amphetamine a known immunomodulator. Tuberculosis being a disease of immune modulation has a varied spectrum of complex interplay of proinflammatory molecules, resistin is one of them. In the present study, we try to explore the trinity of khat addiction, serum resistin level and tuberculosis by correlating the serum resistin level in non khat addicted healthy subjects, khat addicted healthy subjects, and in patients, both khat addicted and non khat addicted, with active tuberculosis. We observed significantly higher resistin level among the apparently healthy khat addicted subjects as compared to non addicted healthy controls. Thereafter, when we compare the resistin levels between khat addicted and non khat addicted TB patients we did not found significant difference between the two groups. However bacillary load was observe to be significantly higher among the khat addicted TB patient as compare to non addicted one. Validation of above results in animal model revealed dose dependant increase in bacillary growth in the Wistar rats treated with khat. Taken together these results suggest the role of khat in immune modulation albeit in the limited frame of resistin level. PMID:26448186

  14. Adiponectin Dysregulation and Insulin Resistance in Type 1 Diabetes

    PubMed Central

    Snell-Bergeon, Janet K.; Erickson, Christopher; Schauer, Irene E.; Bergman, Bryan C.; Rewers, Marian; Maahs, David M.

    2012-01-01

    Context: Type 1 diabetes (T1D) is associated with insulin resistance despite elevated levels of the insulin-sensitizing protein adiponectin. Whether the expected positive correlation between adiponectin and insulin sensitivity is preserved in a T1D population is unknown. Objective: We measured the correlation between total and high-molecular-weight (HMW) adiponectin and insulin sensitivity in T1D patients and nondiabetic controls and identified determinants of adiponectin levels in patients with T1D. Design and Participants: Fasting total and HMW adiponectin were measured in 86 subjects from the Coronary Artery Calcification in T1D (CACTI) cohort (39 T1D, 47 nondiabetic; age 45 ± 8 yr; 55% female). The association of adiponectin levels with insulin sensitivity was analyzed. Setting: The study was conducted at an academic research institute. Methods: Fasting total and HMW adiponectin were measured by RIA and ELISA, respectively. Insulin sensitivity was measured by a hyperinsulinemic-euglycemic clamp. Multivariate linear regression was used to identify determinants of adiponectin levels. Results: Adiponectin levels positively correlated with insulin sensitivity in both subject groups (total adiponectin, r = 0.33 P < 0.05 for T1D, r = 0.29 P < 0.05 controls), but insulin sensitivity was lower in T1D subjects at any given level of total or HMW adiponectin. Adiponectin levels were independently associated with age, gender, and trunk fat, but these variables did not account for increased adiponectin in patients with T1D. Conclusion: Adiponectin levels are positively correlated with insulin sensitivity in T1D patients. However, T1D patients have decreased insulin sensitivity compared with controls at every level of adiponectin, suggesting an important adaptive change of adiponectin set point. PMID:22278421

  15. Leptin: a possible metabolic signal affecting reproduction.

    PubMed

    Spicer, L J

    2001-11-01

    Since its discovery in 1994, leptin, a protein hormone synthesized and secreted by adipose tissue, has been shown to regulate feed intake in several species including sheep and pigs. Although a nimiety of information exists regarding the physiological role of leptin in rodents and humans, the regulation and action of leptin in domestic animals is less certain. Emerging evidence in several species indicates that leptin may also affect the hypothalamo-pituitary-gonadal axis. Leptin receptor mRNA is present in the anterior pituitary and hypothalamus of several species, including sheep. In rats, effects of leptin on GnRH, LH and FSH secretion have been inconsistent, with leptin exhibiting both stimulatory and inhibitory action in vivo and in vitro. Evidence to support direct action of leptin at the level of the gonad indicates that the leptin receptor and its mRNA are present in ovarian tissue of several species, including cattle. These leptin receptors are functional, since leptin inhibits insulin-induced steroidogenesis of both granulosa and thecal cells of cattle in vitro. Leptin receptor mRNA is also found in the testes of rodents. As with the ovary, these receptors are functional, at least in rats, since leptin inhibits hCG-induced testosterone secretion by Leydig cells in vitro. During pregnancy, placental production of leptin may be a major contributor to the increase in maternal leptin in primates but not rodents. However, in both primates and rodents, leptin receptors exist in placental tissues and may regulate metabolism of the fetal-placental unit. As specific leptin immunoassays are developed for domestic animals, in vivo associations may then be made among leptin, body energy stores, dietary energy intake and reproductive function. This may lead to a more definitive role of leptin in domestic animal reproduction. PMID:11872320

  16. Association of Adiponectin Gene Polymorphism with Nonalcoholic Fatty Liver Disease in Taiwanese Patients with Type 2 Diabetes

    PubMed Central

    Hsieh, Ching-Jung; Wang, Pei Wen; Hu, Tsung Hui

    2015-01-01

    Objective Patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) have a higher prevalence of cardiovascular diseases. In this study we investigated the frequency of single nucleotide polymorphisms (SNPs) of several candidate genes associated with NAFLD in Taiwanese patients with type 2 diabetes mellitus (DM) and NAFLD and in those with DM but without fatty liver disease. Methods We enrolled 350 patients with type 2 DM and NAFLD and 209 patients with DM but without NAFLD. Body mass index (BMI), % body fat (% BF), glycated hemoglobin (HbA1c), high molecular weight (HMW) isoform of adiponectin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured. Thirteen SNPs in 5 genes (adiponectin, leptin, peroxisome proliferator-activated receptor alpha, adiponutrin/patatin-like phospholipase domain-containing protein 3 and peroxisome proliferator-activated receptor γ co-activator 1α ) were measured. Results Only adiponectin rs266729 polymorphism was associated with susceptibility to NAFLD (p = 0.001). Subgroup analysis revealed that the proportion of subjects with homozygous genotype GG was higher in patients with NAFLD (31%) than in controls (11%) and that the proportions of heterozygous CG and homozygous CC were higher in controls (37% and 52%, respectively) than in patients with NAFLD (33% and 36%, respectively). Patients with NAFLD carrying the GG genotype of rs266729 showed significantly lower serum HMW adiponectin levels than patients carrying the GC or CC genotype (3.75±0.37 vs. 3.99±0.66 vs. 4.79±0.58 μg/ml, p< 0.001). Body fat and serum HMW adiponectin levels were the strongest predictors of developing NAFLD (p < 0.001 and 0.004, respectively). Conclusions In patients with type 2 diabetes gene polymorphism of adiponectin rs266729 is associated with risk of NAFLD. G allele of rs266729 is associated with

  17. Severe Bronchopulmonary Dysplasia, Growth, Nutrition, and Adipokines at School Age

    PubMed Central

    Suursalmi, Piia; Korhonen, Päivi; Kopeli, Tarja; Nieminen, Riina; Luukkaala, Tiina; Moilanen, Eeva; Tammela, Outi

    2016-01-01

    This study evaluated nutrition and growth in relation to plasma adipokine levels in 21 very-low-birth-weight (VLBW) children with radiographic bronchopulmonary dysplasia (BPD), 19 VLBW controls, and 19 term controls with a median age of 11.3 years. We took anthropometric measurements; assessed plasma levels of adipsin, resistin, adiponectin, and leptin; and analyzed the children’s 3-day food records. Children with BPD had a smaller age-adjusted head circumference and more microcephaly but no other significant growth differences. Daily recommended nutritional intake levels were poorly met but did not differ between the groups. Leptin levels correlated positively with the body mass index standard deviation score in VLBW children. No other associations between adipokine concentrations and growth were found. There were negative correlations between leptin concentrations and fat intake, resistin levels and carbohydrate intake, and adiponectin, adipsin, and leptin levels and energy intake. PMID:27336010

  18. Leptin in human physiology and pathophysiology

    PubMed Central

    Magkos, Faidon; Brinkoetter, Mary; Sienkiewicz, Elizabeth; Dardeno, Tina A.; Kim, Sang-Yong; Hamnvik, Ole-Petter R.; Koniaris, Anastasia

    2011-01-01

    Leptin, discovered through positional cloning 15 years ago, is an adipocyte-secreted hormone with pleiotropic effects in the physiology and pathophysiology of energy homeostasis, endocrinology, and metabolism. Studies in vitro and in animal models highlight the potential for leptin to regulate a number of physiological functions. Available evidence from human studies indicates that leptin has a mainly permissive role, with leptin administration being effective in states of leptin deficiency, less effective in states of leptin adequacy, and largely ineffective in states of leptin excess. Results from interventional studies in humans demonstrate that leptin administration in subjects with congenital complete leptin deficiency or subjects with partial leptin deficiency (subjects with lipoatrophy, congenital or related to HIV infection, and women with hypothalamic amenorrhea) reverses the energy homeostasis and neuroendocrine and metabolic abnormalities associated with these conditions. More specifically, in women with hypothalamic amenorrhea, leptin helps restore abnormalities in hypothalamic-pituitary-peripheral axes including the gonadal, thyroid, growth hormone, and to a lesser extent adrenal axes. Furthermore, leptin results in resumption of menses in the majority of these subjects and, in the long term, may increase bone mineral content and density, especially at the lumbar spine. In patients with congenital or HIV-related lipoatrophy, leptin treatment is also associated with improvements in insulin sensitivity and lipid profile, concomitant with reduced visceral and ectopic fat deposition. In contrast, leptin's effects are largely absent in the obese hyperleptinemic state, probably due to leptin resistance or tolerance. Hence, another emerging area of research pertains to the discovery and/or usefulness of leptin sensitizers. Results from ongoing studies are expected to further increase our understanding of the role of leptin and the potential clinical

  19. Adiponectin gene polymorphisms: Association with childhood obesity

    PubMed Central

    Fraga, Vanêssa Gomes; Gomes, Karina Braga

    2014-01-01

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

  20. Leptin deficiency in maltreated children

    PubMed Central

    Danese, A; Dove, R; Belsky, D W; Henchy, J; Williams, B; Ambler, A; Arseneault, L

    2014-01-01

    Consistent with findings from experimental research in nonhuman primates exposed to early-life stress, children exposed to maltreatment are at high risk of detrimental physical health conditions, such as obesity and systemic inflammation. Because leptin is a key molecule involved in the regulation of both energy balance and immunity, we investigated abnormalities in leptin physiology among maltreated children. We measured leptin, body mass index and C-reactive protein in 170 12-year-old children members of the Environmental-Risk Longitudinal Twin Study, for whom we had prospectively-collected information on maltreatment exposure. We found that maltreated children exhibited blunted elevation in leptin levels in relation to increasing levels of physiological stimuli, adiposity and inflammation, compared with a group of non-maltreated children matched for gender, zygosity and socioeconomic status. These findings were also independent of key potential artifacts and confounders, such as time of day at sample collection, history of food insecurity, pubertal maturation and depressive symptoms. Furthermore, using birth weight as a proxy measure for leptin, we found that physiological abnormalities were presumably not present at birth in children who went on to be maltreated but only emerged over the course of childhood, after maltreatment exposure. Leptin deficiency may contribute to onset, persistence and progression of physical health problems in maltreated children. PMID:25247591

  1. Space radiation exposure persistently increased leptin and IGF1 in serum and activated leptin-IGF1 signaling axis in mouse intestine

    PubMed Central

    Suman, Shubhankar; Kumar, Santosh; Fornace, Albert J.; Datta, Kamal

    2016-01-01

    Travel into outer space is fraught with risk of exposure to energetic heavy ion radiation such as 56Fe ions, which due to its high linear energy transfer (high-LET) characteristics deposits higher energy per unit volume of tissue traversed and thus more damaging to cells relative to low-LET radiation such as γ rays. However, estimates of human health risk from energetic heavy ion exposure are hampered due to lack of tissue specific in vivo molecular data. We investigated long-term effects of 56Fe radiation on adipokines and insulin-like growth factor 1 (IGF1) signaling axis in mouse intestine and colon. Six- to eight-week-old C57BL/6J mice were exposed to 1.6 Gy of 56Fe ions. Serum and tissues were collected up to twelve months post-irradiation. Serum was analyzed for leptin, adiponectin, IGF1, and IGF binding protein 3. Receptor expressions and downstream signaling pathway alterations were studied in tissues. Irradiation increased leptin and IGF1 levels in serum, and IGF1R and leptin receptor expression in tissues. When considered along with upregulated Jak2/Stat3 pathways and cell proliferation, our data supports the notion that space radiation exposure is a risk to endocrine alterations with implications for chronic pathophysiologic changes in gastrointestinal tract. PMID:27558773

  2. Space radiation exposure persistently increased leptin and IGF1 in serum and activated leptin-IGF1 signaling axis in mouse intestine.

    PubMed

    Suman, Shubhankar; Kumar, Santosh; Fornace, Albert J; Datta, Kamal

    2016-01-01

    Travel into outer space is fraught with risk of exposure to energetic heavy ion radiation such as (56)Fe ions, which due to its high linear energy transfer (high-LET) characteristics deposits higher energy per unit volume of tissue traversed and thus more damaging to cells relative to low-LET radiation such as γ rays. However, estimates of human health risk from energetic heavy ion exposure are hampered due to lack of tissue specific in vivo molecular data. We investigated long-term effects of (56)Fe radiation on adipokines and insulin-like growth factor 1 (IGF1) signaling axis in mouse intestine and colon. Six- to eight-week-old C57BL/6J mice were exposed to 1.6 Gy of (56)Fe ions. Serum and tissues were collected up to twelve months post-irradiation. Serum was analyzed for leptin, adiponectin, IGF1, and IGF binding protein 3. Receptor expressions and downstream signaling pathway alterations were studied in tissues. Irradiation increased leptin and IGF1 levels in serum, and IGF1R and leptin receptor expression in tissues. When considered along with upregulated Jak2/Stat3 pathways and cell proliferation, our data supports the notion that space radiation exposure is a risk to endocrine alterations with implications for chronic pathophysiologic changes in gastrointestinal tract. PMID:27558773

  3. Oncogenic role of leptin and Notch interleukin-1 leptin crosstalk outcome in cancer

    PubMed Central

    Lipsey, Crystal C; Harbuzariu, Adriana; Daley-Brown, Danielle; Gonzalez-Perez, Ruben R

    2016-01-01

    Obesity is a global pandemic characterized by high levels of body fat (adiposity) and derived-cytokines (i.e., leptin). Research shows that adiposity and leptin provide insight on the link between obesity and cancer progression. Leptin’s main function is to regulate energy balance. However, obese individuals routinely develop leptin resistance, which is the consequence of the breakdown in the signaling mechanism controlling satiety resulting in the accumulation of leptin. Therefore, leptin levels are often chronically elevated in human obesity. Elevated leptin levels are related to higher incidence, increased progression and poor prognosis of several human cancers. In addition to adipose tissue, cancer cells can also secrete leptin and overexpress leptin receptors. Leptin is known to act as a mitogen, inflammatory and pro-angiogenic factor that induces cancer cell proliferation and tumor angiogenesis. Moreover, leptin signaling induces cancer stem cells, which are involved in cancer recurrence and drug resistance. A novel and complex signaling crosstalk between leptin, Notch and interleukin-1 (IL-1) [Notch, IL-1 and leptin crosstalk outcome (NILCO)] seems to be an important driver of leptin-induced oncogenic actions. Leptin and NILCO signaling mediate the activation of cancer stem cells that can affect drug resistance. Thus, leptin and NILCO signaling are key links between obesity and cancer progression. This review presents updated data suggesting that adiposity affects cancer incidence, progression, and response to treatment. Here we show data supporting the oncogenic role of leptin in breast, endometrial, and pancreatic cancers. PMID:27019796

  4. Serum Resistin and Insulin-Like Growth Factor-1 Levels in Patients with Hypothyroidism and Hyperthyroidism

    PubMed Central

    Eke Koyuncu, Ceren; Turkmen Yildirmak, Sembol; Temizel, Mustafa; Ozpacaci, Tevfik; Gunel, Pinar; Cakmak, Mustafa; Ozbanazi, Yüksel Gülen

    2013-01-01

    Introduction. The aim of this study was to evaluate the serum levels of resistin and insulin-like growth factor-1 (IGF-1) and and also the potential relationship between thyroid function and levels of resistin and IGF-1 in hypothyroid and hyperthyroid patients. Methods. Fifteen cases of hypothyroid (HT), 16 of subclinically hypothyroid (SCHT), 15 of hyperthyroid (HrT), 15 of subclinically hyperthyroid (SCHrT), and 17 healthy individuals have been included in the study. Serum resistin levels were measured using enzyme-linked immunosorbent assay and IGF-1 and thyroid stimulating hormone (TSH) levels by chemiluminescence method. Results. Resistin levels in total HT group were significantly higher than in controls (12.66 ± 6.04 and 8.45 ± 2.90 ng/mL, resp.). In SCHrT subgroup resistin levels were significantly higher than those of controls (14.88 ± 7.73 and 8.45 ± 2.90 ng/mL, resp.). IGF-1 levels were significantly lower in total HT than in total HrT and control groups (117.22 ± 52.03, 155.17 ± 51.67, and 184.00 ± 49.73 ng/mL, resp.). Furthermore IGF-1 levels in HT subgroup were significantly lower compared to controls (123.70 ± 44.03 and 184 ± 49.73 ng/mL, resp.). In SCHT subgroup IGF-1 levels were significantly lower than those of control and SCHrT groups (111.11 ± 59.35, 184.00 ± 49.73, and 166.60 ± 47.87 ng/mL, resp.). There were significant correlations between IGF-1 and TSH in HT subgroup and between resistin and TSH in total HrT group. Conclusion. It was concluded that increased resistin levels are directly related to thyroid dysfunction, and GH/IGF-1 axis is influenced in clinically or subclinically hypothyroidism patients. PMID:23533949

  5. Therapeutic use of recombinant methionyl human leptin.

    PubMed

    Vatier, Camille; Gautier, Jean-François; Vigouroux, Corinne

    2012-10-01

    Recombinant methionyl human leptin (r-metHuLeptin) was first used as a replacement therapy in patients bearing inactivating mutations in the leptin gene. In this indication, it was shown since 1999 to be very efficient in inducing a dramatic weight loss in rare children and adults with severe obesity due to the lack of leptin. These first clinical trials clearly showed that r-metHuLeptin acted centrally to reduce food intake, inducing loss of fat mass, and to correct metabolic alterations, immune and neuroendocrine defects. A few years later, r-metHuLeptin was also shown to reverse the metabolic complications associated with lipodystrophic syndromes, due to primary defects in fat storage, which induce leptin deficiency. The beneficial effects, which could be mediated by central and/or peripheral mechanisms, are thought to mainly involve the lowering effects of leptin on ectopic lipid storage, in particular in liver and muscles, reducing insulin resistance. Interestingly, r-metHuLeptin therapy also reversed the hypothalamic-pituitary-gonadal axis dysfunctions associated with hypothalamic amenorrhea. However, if r-metHuLeptin treatment has been shown to be dramatically efficient in leptin-deficient states, its very limited effect in inducing weight loss in common obese patients revealed that, in patients with adequate leptin secretion, mechanisms of leptin resistance and leptin tolerance prevent r-metHuLeptin from inducing any additional effects. This review will present the current data about the effects of r-metHuLeptin therapy in humans, and discuss the recent perspectives of this therapy in new indications. PMID:22464954

  6. Short Sleep Duration Is Associated with Reduced Leptin, Elevated Ghrelin, and Increased Body Mass Index

    PubMed Central

    2004-01-01

    Background Sleep duration may be an important regulator of body weight and metabolism. An association between short habitual sleep time and increased body mass index (BMI) has been reported in large population samples. The potential role of metabolic hormones in this association is unknown. Methods and Findings Study participants were 1,024 volunteers from the Wisconsin Sleep Cohort Study, a population-based longitudinal study of sleep disorders. Participants underwent nocturnal polysomnography and reported on their sleep habits through questionnaires and sleep diaries. Following polysomnography, morning, fasted blood samples were evaluated for serum leptin and ghrelin (two key opposing hormones in appetite regulation), adiponectin, insulin, glucose, and lipid profile. Relationships among these measures, BMI, and sleep duration (habitual and immediately prior to blood sampling) were examined using multiple variable regressions with control for confounding factors. A U-shaped curvilinear association between sleep duration and BMI was observed. In persons sleeping less than 8 h (74.4% of the sample), increased BMI was proportional to decreased sleep. Short sleep was associated with low leptin (p for slope = 0.01), with a predicted 15.5% lower leptin for habitual sleep of 5 h versus 8 h, and high ghrelin (p for slope = 0.008), with a predicted 14.9% higher ghrelin for nocturnal (polysomnographic) sleep of 5 h versus 8 h, independent of BMI. Conclusion Participants with short sleep had reduced leptin and elevated ghrelin. These differences in leptin and ghrelin are likely to increase appetite, possibly explaining the increased BMI observed with short sleep duration. In Western societies, where chronic sleep restriction is common and food is widely available, changes in appetite regulatory hormones with sleep curtailment may contribute to obesity. PMID:15602591

  7. Adiponectin and Interleukin-6, But Not Adipose Tissue, Are Associated with Worse Neurocognitive Function in HIV-Infected Men

    PubMed Central

    Lake, Jordan E.; Vo, Quynh T.; Jacobson, Lisa P.; Sacktor, Ned; Miller, Eric N.; Post, Wendy S.; Becker, James T.; Palella, Frank J.; Ragin, Ann; Martin, Eileen; Munro, Cynthia A.; Brown, Todd T.

    2014-01-01

    Background Generalized obesity has been associated with cognitive decline, a process potentially mediated by adipocytokines. The effects of regional adipose tissue (AT) on cognition, however, are not well understood. We explored cross-sectional relationships between regional AT, adipocytokines, inflammatory markers and neuropsychological (NP) test scores among HIV+ and HIV− men enrolled in the Multicenter AIDS Cohort Study. Methods Visceral, subcutaneous abdominal and subcutaneous thigh AT areas were quantified by computed tomography (CT). NP tests (Trail Making Test parts A and B and Symbol Digit Modalities) obtained within two years of CT screened for psychomotor speed and executive function. Adiponectin, leptin, interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) were measured. Results Of 509 HIV+ and 271 HIV− participants, HIV+ men (98% on ART, 81% HIV-1 RNA <50copies/mL) had lower median subcutaneous AT and adiponectin levels and higher hs-CRP levels, but visceral AT, BMI, IL-6 and NP scores did not vary by HIV serostatus. In multivariable analysis, older age, ≤high school education and African American race, but not AT area or site, were associated with worse NP test scores among all participants. In HIV+ only, higher adiponectin and IL-6 were associated with worse cognitive function independent of AT area. No HIV-specific factors were associated with NP test scores. Conclusions Demographic factors were associated with NP test performance, but regional adiposity was not. In HIV+ only, higher adiponectin and IL-6 were associated with worse NP test scores, supporting a role for chronic inflammation and adipocytokine imbalance in neurocognitive decline in HIV+ persons. PMID:25810377

  8. Maternal adiponectin controls milk composition to prevent neonatal inflammation.

    PubMed

    Jin, Zixue; Du, Yang; Schwaid, Adam G; Asterholm, Ingrid W; Scherer, Philipp E; Saghatelian, Alan; Wan, Yihong

    2015-04-01

    Adiponectin is an important adipokine. Increasing evidence suggests that altered adiponectin levels are linked with metabolic and inflammatory disorders. Here we report an important yet previously unrecognized function of adiponectin in lactation by which maternal adiponectin determines the inflammatory status in the nursing neonates. Surprisingly, both maternal adiponectin overexpression in the transgenic mice and maternal adiponectin deletion in the knockout mice lead to systemic inflammation in the pups, manifested as transient hair loss. However, distinct mechanisms are involved. Adiponectin deficiency triggers leukocyte infiltration and production of inflammatory cytokines in the lactating mammary gland. In contrast, adiponectin overabundance increases lipid accumulation in the lactating mammary gland, resulting in excessive long-chain saturated fatty acids in milk. Interestingly, in both cases, the inflammation and alopecia in the pups can be rescued by Toll-like receptor (TLR)-2/4 deletion because TLR2/4 double-knockout pups are resistant. Mechanistically, long-chain saturated fatty acid activation of inflammatory genes is TLR2/4 dependent and can be potentiated by proinflammatory cytokines, indicating that the inflammatory stimuli in both scenarios functionally converge by activating the TLR2/4 signaling. Therefore, our findings reveal adiponectin as a dosage-dependent regulator of lactation homeostasis and milk quality that critically controls inflammation in the nursing neonates. Furthermore, these results suggest that inflammatory infantile disorders may result from maternal adiponectin dysregulation that can be treated by TLR2/4 inhibition. PMID:25590242

  9. Leptin signaling and Alzheimer’s disease

    PubMed Central

    Marwarha, Gurdeep; Ghribi, Othman

    2012-01-01

    Leptin, an adipocytokine produced in the peripheral system as well as in the brain, is implicated in obesity, food intake, glucose homeostasis, and energy expenditure. Leptin expression levels and signaling pathways may also be linked to the pathophysiology of neurodegenerative diseases including Alzheimer’s disease. Epidemiological studies have demonstrated that higher circulating leptin levels are associated with lower risk of dementia including Alzheimer’s disease, and lower circulating levels of leptin have been reported in patients with Alzheimer’s disease. Leptin receptors are highly expressed in the hippocampus, a brain area involved in learning and memory and severely affected during the course of Alzheimer’s disease. In laboratory studies, several in vivo and in vitro studies have shown that leptin supplementation decreases amyloid-β (Aβ) production and tau phosphorylation, two major biochemical events that play a key role in the pathogenesis of Alzheimer’s disease. In this review, we will review the structure of leptin, the type of receptors of leptin in the brain, the various biological functions attributed to this adipocytokine, the signaling pathways that govern leptin actions, and the potential role of leptin in the pathophysiology of Alzheimer’s disease. Leptin exerts its functions by binding to the leptin receptor (ObR). This binding can involve several signaling pathways including JAK/STAT pathway, ERK pathway and the PI3K/Akt/mTOR Pathway. Modulation of these pathways leads to the regulation of a multitude of functions that define the intricate involvement of leptin in various physiological tasks. In this review, we will specifically relate the potential involvement of leptin signaling in Alzheimer’s disease based on work published by several laboratories including ours. All this work points to leptin as a possible target for developing supplementation therapies for reducing the progression of Alzheimer’s disease. PMID:23383396

  10. Sitagliptin decreases ventricular arrhythmias by attenuated glucose-dependent insulinotropic polypeptide (GIP)-dependent resistin signalling in infarcted rats.

    PubMed

    Lee, Tsung-Ming; Chen, Wei-Ting; Chang, Nen-Chung

    2016-01-01

    Myocardial infarction (MI) was associated with insulin resistance, in which resistin acts as a critical mediator. We aimed to determine whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, can attenuate arrhythmias by regulating resistin-dependent nerve growth factor (NGF) expression in postinfarcted rats. Normoglycaemic male Wistar rats after ligating coronary artery were randomized to either vehicle or sitagliptin for 4 weeks starting 24 h after operation. Post-infarction was associated with increased myocardial noradrenaline [norepinephrine (NE)] levels and sympathetic hyperinnervation. Compared with vehicle, sympathetic innervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis of tyrosine hydroxylase, growth-associated factor 43 and neurofilament and western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the sitagliptin-treated infarcted rats were significantly lower than those in vehicle. Furthermore, sitagliptin was associated with reduced resistin expression and increased Akt activity. Ex vivo studies showed that glucose-dependent insulinotropic polypeptide (GIP) infusion, but not glucagon-like peptide-1 (GLP-1), produced similar reduction in resistin levels to sitagliptin in postinfarcted rats. Furthermore, the attenuated effects of sitagliptin on NGF levels can be reversed by wortmannin (a phosphatidylinositol 3-kinase antagonist) and exogenous resistin infusion. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation in the non-diabetic infarcted rats. Sitagliptin attenuated resistin expression via the GIP-dependent pathway, which inhibited sympathetic innervation through a signalling pathway involving phosphatidylinositol 3-kinase (PI3K) and Akt protein. PMID:26811539

  11. Sitagliptin decreases ventricular arrhythmias by attenuated glucose-dependent insulinotropic polypeptide (GIP)-dependent resistin signalling in infarcted rats

    PubMed Central

    Lee, Tsung-Ming; Chen, Wei-Ting; Chang, Nen-Chung

    2016-01-01

    Myocardial infarction (MI) was associated with insulin resistance, in which resistin acts as a critical mediator. We aimed to determine whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, can attenuate arrhythmias by regulating resistin-dependent nerve growth factor (NGF) expression in postinfarcted rats. Normoglycaemic male Wistar rats after ligating coronary artery were randomized to either vehicle or sitagliptin for 4 weeks starting 24 h after operation. Post-infarction was associated with increased myocardial noradrenaline [norepinephrine (NE)] levels and sympathetic hyperinnervation. Compared with vehicle, sympathetic innervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis of tyrosine hydroxylase, growth-associated factor 43 and neurofilament and western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the sitagliptin-treated infarcted rats were significantly lower than those in vehicle. Furthermore, sitagliptin was associated with reduced resistin expression and increased Akt activity. Ex vivo studies showed that glucose-dependent insulinotropic polypeptide (GIP) infusion, but not glucagon-like peptide-1 (GLP-1), produced similar reduction in resistin levels to sitagliptin in postinfarcted rats. Furthermore, the attenuated effects of sitagliptin on NGF levels can be reversed by wortmannin (a phosphatidylinositol 3-kinase antagonist) and exogenous resistin infusion. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation in the non-diabetic infarcted rats. Sitagliptin attenuated resistin expression via the GIP-dependent pathway, which inhibited sympathetic innervation through a signalling pathway involving phosphatidylinositol 3-kinase (PI3K) and Akt protein. PMID:26811539

  12. The role of leptin in obesity and the potential for leptin replacement therapy.

    PubMed

    Feng, Helin; Zheng, Lihua; Feng, Zhangying; Zhao, Yaheng; Zhang, Ning

    2013-08-01

    Leptin (from the Greek word "lepto'' meaning "thin") is a 167-amino acid peptide hormone encoded by the obesity (ob) gene and secreted by white adipocytes. Blood leptin concentrations are increased in obese individuals. Leptin is a satiety hormone that provides negative feedback to the hypothalamus, controlling appetite and energy expenditure. Leptin binds to presynaptic GABAergic neurons to produce its effect, raising the distinct possibility that GABAergic axon terminals are the ultimate subcellular site of action for its effects. Released into the circulation, leptin crosses the blood-brain barrier and binds to leptin receptors, influencing the activity of various hypothalamic neurons, as well as encoding orexigenic and anorexigenic neuropeptides. Moreover, leptin affects a wide range of metabolic functions in the peripheral tissue. In this review, we discuss some physiologic functions of leptin, including effects on obesity and some effects of leptin replacement therapy. PMID:23274948

  13. Goldfish Leptin-AI and Leptin-AII: Function and Central Mechanism in Feeding Control

    PubMed Central

    Yan, Ai-Fen; Chen, Ting; Chen, Shuang; Ren, Chun-Hua; Hu, Chao-Qun; Cai, Yi-Ming; Liu, Fang; Tang, Dong-Sheng

    2016-01-01

    In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous studies examining leptin in fish feeding were performed with mammalian leptins, which share very low sequence homologies with fish leptins. To elucidate the function and mechanism of endogenous fish leptins in feeding regulation, recombinant goldfish leptin-AI and leptin-AII were expressed in methylotrophic yeast and purified by immobilized metal ion affinity chromatography (IMAC). By intraperitoneal (IP) injection, both leptin-AI and leptin-AII were shown to inhibit the feeding behavior and to reduce the food consumption of goldfish in 2 h. In addition, co-treatment of leptin-AI or leptin-AII could block the feeding behavior and reduce the food consumption induced by neuropeptide Y (NPY) injection. High levels of leptin receptor (lepR) mRNA were detected in the hypothalamus, telencephalon, optic tectum and cerebellum of the goldfish brain. The appetite inhibitory effects of leptins were mediated by downregulating the mRNA levels of orexigenic NPY, agouti-related peptide (AgRP) and orexin and upregulating the mRNA levels of anorexigenic cocaine-amphetamine-regulated transcript (CART), cholecystokinin (CCK), melanin-concentrating hormone (MCH) and proopiomelanocortin (POMC) in different areas of the goldfish brain. Our study, as a whole, provides new insights into the functions and mechanisms of leptins in appetite control in a fish model. PMID:27249000

  14. Goldfish Leptin-AI and Leptin-AII: Function and Central Mechanism in Feeding Control.

    PubMed

    Yan, Ai-Fen; Chen, Ting; Chen, Shuang; Ren, Chun-Hua; Hu, Chao-Qun; Cai, Yi-Ming; Liu, Fang; Tang, Dong-Sheng

    2016-01-01

    In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous studies examining leptin in fish feeding were performed with mammalian leptins, which share very low sequence homologies with fish leptins. To elucidate the function and mechanism of endogenous fish leptins in feeding regulation, recombinant goldfish leptin-AI and leptin-AII were expressed in methylotrophic yeast and purified by immobilized metal ion affinity chromatography (IMAC). By intraperitoneal (IP) injection, both leptin-AI and leptin-AII were shown to inhibit the feeding behavior and to reduce the food consumption of goldfish in 2 h. In addition, co-treatment of leptin-AI or leptin-AII could block the feeding behavior and reduce the food consumption induced by neuropeptide Y (NPY) injection. High levels of leptin receptor (lepR) mRNA were detected in the hypothalamus, telencephalon, optic tectum and cerebellum of the goldfish brain. The appetite inhibitory effects of leptins were mediated by downregulating the mRNA levels of orexigenic NPY, agouti-related peptide (AgRP) and orexin and upregulating the mRNA levels of anorexigenic cocaine-amphetamine-regulated transcript (CART), cholecystokinin (CCK), melanin-concentrating hormone (MCH) and proopiomelanocortin (POMC) in different areas of the goldfish brain. Our study, as a whole, provides new insights into the functions and mechanisms of leptins in appetite control in a fish model. PMID:27249000

  15. 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.

  16. Structure, production and signaling of leptin

    PubMed Central

    Münzberg, Heike; Morrison, Christopher D.

    2014-01-01

    The cloning of leptin in 1994 was an important milestone in obesity research. In those days obesity was stigmatized as a condition caused by lack of character and self-control. Mutations in either leptin or its receptor were the first single gene mutations found to cause morbid obesity, and it is now appreciated that obesity is caused by a dysregulation of central neuronal circuits. From the first discovery of the leptin deficient obese mouse (ob/ob), to the cloning of leptin (ob aka lep) and leptin receptor (db aka lepr) genes, much has been learned about leptin and its action in the central nervous system. The initial high hopes that leptin would cure obesity were quickly dampened by the discovery that most obese humans have increased leptin levels and develop leptin resistance. Nevertheless, leptin target sites in the brain represent an excellent blueprint for distinct neuronal circuits that control energy homeostasis. A better understanding of the regulation and interconnection of these circuits will further guide and improve the development of safe and effective interventions to treat obesity. This review will highlight our current knowledge about the hormone leptin, its signaling pathways and its central actions to mediate distinct physiological functions. PMID:25305050

  17. Ten years of leptin replacement therapy.

    PubMed

    Paz-Filho, G; Wong, M-L; Licinio, J

    2011-05-01

    Leptin is a pleiotropic cytokine-like hormone that is involved in the regulation of energy intake and expenditure, neuroendocrine function, immunity and lipid and glucose metabolism. The few humans with genetically based leptin deficiency provide a unique model to assess those effects. We have identified five Turkish patients (one male and two female adults; one boy and one girl) with congenital leptin deficiency due to a missense mutation in the leptin gene. Four of these patients were treated with physiological doses of recombinant methionyl human leptin. Body composition, brain structure and function, behaviour, immunity and endocrine and metabolic parameters were evaluated before and during treatment. Our results showed that leptin has peripheral, hypothalamic and extra-hypothalamic effects. Within the endocrine system, leptin regulates the circadian rhythms of cortisol, thyroid-stimulating hormone, luteinizing hormone and follicle-stimulating hormone. In the brain, leptin controls energy balance and body weight, and plays a role on neurogenesis and brain function. Leptin is a key element of the adiposinsular axis, enhances immune response, and regulates inflammation, coagulation, fibrinolysis and platelet aggregation. Our 10-year experience in treating these unique patients provided valuable data on the peripheral and central effects of leptin. Those results can be taken into account for the development of leptin-based therapies for other diseases. PMID:21410864

  18. Dietary intake and ghrelin and leptin changes after sleeve gastrectomy

    PubMed Central

    Zavadilová, Vladislava; Holéczy, Pavol; Švagera, Zdeněk; Švorc, Pavol; Foltys, Aleš; Zonča, Pavel

    2014-01-01

    Introduction Surgical intervention in obesity is today the most effective treatment method in high level obesity management. Bariatric interventions not only ensure body weight reduction, but may influence dietary habits. Aim To assess changes in adipose hormones and dietary habits in obese patients after sleeve gastrectomy. Material and methods The study set comprised 37 subjects (29 females and 8 males) 24 to 68 years old with body mass index 43.0 ±4.9 kg/m2. Pre-operative examination included baseline measurements of body composition. Dietary habits and intake frequency were monitored by a questionnaire method. Follow-up examinations were carried out in a scope identical to the pre-operative examination, 6 and 12 months after surgery, respectively. Results The average patient weight loss 12 months after surgery was 31.7 kg. Excess weight loss was 55.2 ±20.6%. Patients reported reduced appetite (p < 0.001), increasingly regular food intake (p < 0.001), intake of more meal portions per day (p = 0.003) and a decrease in consuming the largest portions during the afternoon and evening (p = 0.030). Plasma levels of fasting glucose, leptin and ghrelin significantly decreased (p = 0.006; p = 0.0.043); in contrast, the level of adiponectin significantly increased (p < 0.001). Conclusions Sleeve gastrectomy and follow-up nutritional therapy resulted in a significant body weight reduction within 1 year after surgery. An improvement of certain dietary habits in patients was registered. At 12 months after surgery, there were no statistically significant differences in decreases in ghrelin and leptin concentrations between patients without changed appetite and those reporting decreased appetite. PMID:25561993

  19. Adiponectin--its role in metabolism and beyond.

    PubMed

    Stefan, N; Stumvoll, M

    2002-09-01

    Adiponectin is a recently identified adipose tissue-derived protein (adipocytokine) with important metabolic effects. It is exclusively expressed in adipose tissue and released into the circulation. Adiponectin expression and/or secretion is increased by insulin like growth factor-1 and ionomycin, and decreased by tumor necrosis factor-alpha, glucocorticoids, beta-adrenergic agonists and cAMP. Data for insulin are somewhat inconclusive. Moreover, adiponectin expression and secretion are increased by activators of peroxisome proliferator-activated receptor (PPAR)-gamma. Besides inhibiting inflammatory pathways, recombinant adiponectin increases insulin sensitivity and improves glucose tolerance in various animal models. This insulin-sensitizing effect appears to be mostly attributable to enhanced suppression of glucose production, but beneficial effects on muscle cannot be excluded. In humans, plasma adiponectin concentrations exceed those of any other hormone by a thousand times; they decrease with obesity and are positively associated with whole-body insulin sensitivity. Therefore, low adiponectin may contribute to the decrease in whole-body insulin sensitivity that accompanies obesity. Furthermore, there is increasing evidence that genetic variants in the adiponectin gene itself and/or in genes encoding adiponectin-regulatory proteins--such as PPAR-gamma--may be associated with hypoadiponectinemia, insulin resistance and type 2 diabetes. This suggests that adiponectin may reflect PPAR-gamma activity in vivo. Finally, reversal or alleviation of hypoadiponectinemia may represent a target for development of drugs improving insulin sensitivity and glucose tolerance. PMID:12384822

  20. Postoperative Adiponectin Levels in Pediatric Patients Undergoing Open Heart Surgery

    PubMed Central

    Thaler, A.; Kanety, H.; Avni, T.; Mishali, D.; Hemi, R.; Yissaschar, E.; Pariente, C.; Paret, G.; Modan-Moses, D.

    2013-01-01

    Background. Adipose tissue is an important endocrine organ that secretes cytokines, including adiponectin, levels of which are negatively correlated with the severity of the inflammatory process. Aim. To assess the time course of adiponectin levels following open heart surgery with cardiopulmonary bypass and its correlation with early postoperative outcomes. Materials and Methods. Blood samples were obtained from 24 children undergoing cardiac surgery and analyzed for adiponectin, C-reactive protein, and other inflammatory markers. Results. Baseline adiponectin levels were negatively correlated with patients' preoperative weight and age. Postoperative adiponectin levels decreased compared to baseline (P = 0.01) and correlated negatively with duration of cardiopulmonary bypass (r = −0.438, P = 0.037), length of stay in the pediatric intensive care unit (r = −0.457, P = 0.025), and the inotropic score (r = −0.471, P = 0.02). Adiponectin levels were positively correlated with sVCAM 1 levels; however, there was no correlation between adiponectin levels and sP selectin, tPA, MCP1, and sCD40. Conclusions. The inflammatory response after open heart surgery with cardiopulmonary bypass is associated with a reduction in adiponectin levels. Prolonged or more complicated surgery induced a more substantial inflammatory process characterized by a significant reduction in adiponectin levels over time and a delayed return to baseline levels. PMID:24224162

  1. Adipokines as emerging depression biomarkers: a systematic review and meta-analysis.

    PubMed

    Carvalho, André F; Rocha, Davi Q C; McIntyre, Roger S; Mesquita, Lucas M; Köhler, Cristiano A; Hyphantis, Thomas N; Sales, Paulo M G; Machado-Vieira, Rodrigo; Berk, Michael

    2014-12-01

    Adiponectin, leptin and resistin may play a role in the pathophysiology of major depressive disorder (MDD). However, differences in peripheral levels of these hormones are inconsistent across diagnostic and intervention studies. Therefore, we performed meta-analyses of diagnostic studies (i.e., MDD subjects versus healthy controls) and intervention investigations (i.e., pre-vs. post-antidepressant treatment) in MDD. Adiponectin (N = 1278; Hedge's g = -0.35; P = 0.16) and leptin (N = 893; Hedge's g = -0.018; P = 0.93) did not differ across diagnostic studies. Meta-regression analyses revealed that gender and depression severity explained the heterogeneity observed in adiponectin diagnostic studies, while BMI and the difference in BMI between MDD individuals and controls explained the heterogeneity of leptin diagnostic studies. Subgroup analyses revealed that adiponectin peripheral levels were significantly lower in MDD participants compared to controls when assayed with RIA, but not ELISA. Leptin levels were significantly higher in individuals with mild/moderate depression versus controls. Resistin serum levels were lower in MDD individuals compared to healthy controls (N = 298; Hedge's g = -0.25; P = 0.03). Leptin serum levels did not change after antidepressant treatment. However, heterogeneity was significant and sample size was low (N = 108); consequently meta-regression analysis could not be performed. Intervention meta-analyses could not be performed for adiponectin and resistin (i.e., few studies met inclusion criteria). In conclusion, this systematic review and meta-analysis underscored that relevant moderators/confounders (e.g., BMI, depression severity and type of assay) should be controlled for when considering the role of leptin and adiponectin as putative MDD diagnostic biomarkers. PMID:25183029

  2. Crystal structures of the human adiponectin receptors.

    PubMed

    Tanabe, Hiroaki; Fujii, Yoshifumi; Okada-Iwabu, Miki; Iwabu, Masato; Nakamura, Yoshihiro; 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

    2015-04-16

    Adiponectin stimulation of its receptors, AdipoR1 and AdipoR2, increases the activities of 5' AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR), 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 receptors. 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 G-protein-coupled receptors, enclose a large cavity where three conserved histidine residues coordinate a zinc ion. The zinc-binding structure may have a role in the adiponectin-stimulated AMPK phosphorylation and UCP2 upregulation. Adiponectin may broadly interact with the extracellular face, rather than the carboxy-terminal 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

  3. Targeted leptin receptor blockade: Role of VTA and NTS leptin receptors in body weight homeostasis

    PubMed Central

    Matheny, M.; Strehler, K.Y.E.; King, M.; Tümer, N.; Scarpace, P. J.

    2014-01-01

    The present investigation examined whether leptin stimulation of ventral tegmental area (VTA) or nucleus of the solitary tract (NTS) has a role in body weight homeostasis independent of the medial basal hypothalamus (MBH). To this end, recombinant adeno-associated viral techniques were employed to target leptin overexpression or overexpression of a dominant negative leptin mutant (Leptin Antagonist). Leptin Antagonist overexpression in MBH or VTA increased food intake and body weight to similar extents over 14 days in rats. Simultaneous overexpression of leptin in VTA with antagonist in MBH resulted in food intake and body weight gain that were less than with control treatment but greater than with leptin alone in VTA. Notably, leptin overexpression in VTA increased P-STAT3 in MBH along with VTA, and Leptin Antagonist overexpression in the VTA partially attenuated P-STAT3 levels in MBH. Interestingly, leptin antagonist overexpression elevated body weight gain, but leptin overexpression in the NTS failed to modulate either food intake or body weight despite increased P-STAT3. These data suggest that leptin function in the VTA participates in the chronic regulation of food consumption and body weight in response to stimulation or blockade of VTA leptin receptors. Moreover, one component of VTA-leptin action appears to be independent of the MBH, and another component appears to be related to leptin receptor-mediated P-STAT3 activation in the MBH. Finally, leptin receptors in the NTS are necessary for normal energy homeostasis, but appear to have mostly a permissive role. Direct leptin activation of NTS slightly increases UCP1, but has little effect on food consumption or body weight. PMID:24920667

  4. Correlation of leptin and soluble leptin receptor levels with anthropometric parameters in mother-newborn pairs

    PubMed Central

    Marino-Ortega, Linda A; Molina-Bello, Adiel; Polanco-García, Julio C; Muñoz-Valle, José F; Salgado-Bernabé, Aralia B; Guzmán-Guzmán, Iris P; Parra-Rojas, Isela

    2015-01-01

    The aim of this study was to investigate if anthropometric parameters are associated with both leptin and soluble leptin receptor (sLEPR) levels in newborns and their mothers. This cross-sectional study was performed in 118 mother-newborn pairs. The venous blood sample of mothers was taken before delivery and immediately after delivery an umbilical cord blood sample was collected. Levels of leptin and sLEPR in maternal and umbilical cord sera were assessed by ELISA. Maternal serum concentration of leptin and sLEPR (6.2 and 25.7 ng/ml, respectively) were higher than in umbilical cord blood (2.4 and 14.2 ng/ml, respectively). However, the newborns and their mothers had higher sLEPR levels than leptin levels. In mothers was observed that leptin levels increase with weight gain in pregnancy and decreased sLEPR levels. Cord leptin levels correlated with neonatal birth weight and length, the body circumferences, placental weight and maternal leptin levels. Cord sLEPR levels correlated with maternal sLEPR and leptin levels. Maternal serum concentration of leptin correlated with pre-pregnancy BMI, weight gain, cord sLEPR and leptin levels. Maternal sLEPR concentration correlated with cord sLEPR levels. The leptin and sLEPR levels in mother-newborn pairs are related with anthropometric parameters and an inverse correlation between leptin levels and sLEPR was observed in pairs. PMID:26379933

  5. Tracing the movement of adiponectin in a parabiosis model of wild-type and adiponectin-knockout mice

    PubMed Central

    Nakatsuji, Hideaki; Kishida, Ken; Sekimoto, Ryohei; Funahashi, Tohru; Shimomura, Iichiro

    2014-01-01

    Adiponectin is exclusively synthesized by adipocytes and exhibits anti-diabetic, anti-atherosclerotic and anti-inflammatory properties. Hypoadiponectinemia is associated in obese individuals with insulin resistance and atherosclerosis. However, the mechanisms responsible for hypoadiponectinemia remain unclear. Here, we investigated adiponectin movement using hetero parabiosis model of wild type (WT) and adiponectin-deficient (KO) mice. WT mice were parabiosed with WT mice (WT–WT) or KO mice (WT–KO) and adiponectin levels were measured serially up to 63 days after surgery. In the WT–KO parabiosis model, circulating adiponectin levels of the WT partners decreased rapidly, on the other hand, those of KO partners increased, and then these reached comparable levels each other at day 7. Circulating adiponectin levels decreased further to the detection limit of assay, and remained low up to day 63. However, adiponectin protein was detected in the adipose tissues of not only the WT partner but also WT–KO mice. In the diet-induced obesity model, high adiponectin protein levels were detected in adipose stromal vascular fraction of diet-induced obese KO partner, without changes in its binding proteins. The use of parabiosis experiments shed light on movement of native adiponectin among different tissues such as the state of hypoadiponectinemia in obesity. PMID:24918039

  6. Modulation of leptin resistance by food compounds.

    PubMed

    Aragonès, Gerard; Ardid-Ruiz, Andrea; Ibars, Maria; Suárez, Manuel; Bladé, Cinta

    2016-08-01

    Leptin is mainly secreted by white adipose tissue and regulates energy homeostasis by inhibiting food intake and stimulating energy expenditure through its action in neuronal circuits in the brain, particularly in the hypothalamus. However, hyperleptinemia coexists with the loss of responsiveness to leptin in common obese conditions. This phenomenon has been defined as leptin resistance and the restoration of leptin sensitivity is considered to be a useful strategy to treat obesity. This review summarizes the existing literature on potentially valuable nutrients and food components to reverse leptin resistance. Notably, several food compounds, such as teasaponins, resveratrol, celastrol, caffeine, and taurine among others, are able to restore the leptin signaling in neurons by overexpressing anorexigenic peptides (proopiomelanocortin) and/or repressing orexigenic peptides (neuropeptide Y/agouti-related peptide), thus decreasing food intake. Additionally, some nutrients, such as vitamins A and D, can improve leptin transport through the blood-brain barrier. Therefore, food components can improve leptin resistance by acting at different levels of the leptin pathway; moreover, some compounds are able to target more than one feature of leptin resistance. However, systematic studies are necessary to define the actual effectiveness of each compound. PMID:26842874

  7. Pharmacokinetics of leptin in female mice.

    PubMed

    Hart, R A; Dobos, R C; Agnew, L L; Tellam, R L; McFarlane, J R

    2016-06-20

    Pharmacokinetics of leptin in mammals has received limited attention and only one study has examined more than two time points and this was in ob/ob mice. This study is the first to observe the distribution of leptin over a time course in female mice. A physiologic dose (12 ng) of radiolabelled leptin was injected in adult female mice via the lateral tail vein and tissues were dissected out and measured for radioactivity over a time course up to two hours. Major targets for administered leptin included the liver, kidneys, gastrointestinal tract and the skin while the lungs had high concentrations of administered leptin per gram of tissue. Leptin was also found to enter the lumen of the digestive tract intact from the plasma. Very little of the dose (<1 %) was recovered from the brain at any time. Consequently we confirm that the brain is not a major target for leptin from the periphery, although it may be very sensitive to leptin that does get to the hypothalamus. Several of the major targets (GI tract, skin and lungs) for leptin form the interface for the body with the environment, and given the ability of leptin to modulate immune function, this may represent a priming effect for tissues to respond to damage and infection. PMID:26447522

  8. Leptin Effect on Acetylation and Phosphorylation of Pgc1α in Muscle Cells Associated With Ampk and Akt Activation in High-Glucose Medium.

    PubMed

    García-Carrizo, Francisco; Nozhenko, Yuriy; Palou, Andreu; Rodríguez, Ana M

    2016-03-01

    Leptin is crucial in energy metabolism, including muscle regulation. Peroxisome proliferator activated receptor gamma co-activator 1α (PGC1α) orchestrates energy metabolism and is tightly controlled by post-translational covalent modifications such as phosphorylation and acetylation. We aimed to further the knowledge of PGC1α control by leptin (at physiological levels) in muscle cells by time-sequentially analysing the activation of AMP activated protein kinase (AMPK), P38 mitogen-activated protein kinase (P38 MAPK) and Akt (Protein kinase B)--all known to phosphorylate PGC1α and to be involved in the regulation of its acetylation status--in C2C12 myotubes placed in a high-glucose serum-free medium. We also studied the protein levels of PGC1α, Sirtuin 1, adiponectin, COX IV, mitofusin 2 (Mfn2), and pyruvate dehydrogenase kinase 4 (PDK4). Our main findings suggest an important role of leptin regulating AMPK and Akt phosphorylation, Mfn2 induction and PGC1α acetylation status, with the novelty that the latter in transitorily increased in response to leptin, an effect dependent, at least in part, on AMPK regulation. These post-translational reversible changes in PGC1α in response to leptin, especially the increase in acetylation status, may be related to the physiological role of the hormone in modulating muscle cell response to the physiological/nutritional status. PMID:26218179

  9. Protracted Upregulation of Leptin and IGF1 is Associated with Activation of PI3K/Akt and JAK2 Pathway in Mouse Intestine after Ionizing Radiation Exposure

    PubMed Central

    Suman, Shubhankar; Kallakury, Bhaskar V. S.; Fornace, Albert J.; Datta, Kamal

    2015-01-01

    Ionizing radiation is a known risk factor for gastrointestinal (GI) pathologies including cancer. Hormones and related signaling crosstalk, which could contribute to radiation-induced persistent pathophysiologic changes in the small intestine and colon, remain to be explored. The current study assessed perturbation of GI homeostasis-related hormones and signaling pathways at the systemic as well as at the tissue level in small intestine and colon. Mice (6-8 week old C57BL/6J) were exposed to 2 Gy γ radiation, serum and tissue samples were collected, and insulin like growth factor 1 (IGF-1) and leptin signaling were assessed two or twelve months after radiation exposure. Serum levels of IGF-1, IGF binding protein 3 (IGFBP3), leptin, and adiponectin were altered at these times after irradiation. Radiation was associated with increased IGF1 receptor (IGF1R) and obesity (leptin) receptor (Ob-R), decreased adiponectin receptor 1 (Adipo-R1) and 2 (Adipo-R2), and increased Ki-67 levels in small intestine and colon at both time points. Immunoblot analysis further showed increased IGF1R and Ob-R, and decreased Adipo-R2. Additionally, upregulation of PI3K/Akt and JAK2 signaling, which are downstream of IGF1 and leptin, was also observed in irradiated samples at both time points. These results when considered along with increased cell proliferation in the small intestine and colon demonstrate for the first time that ionizing radiation can persistently increase IGF1 and leptin and activate downstream proliferative pathways, which may contribute to GI functional alterations and carcinogenesis. PMID:25678846

  10. Changes in profile of lipids and adipokines in patients with newly diagnosed hypothyroidism and hyperthyroidism.

    PubMed

    Chen, Yanyan; Wu, Xiafang; Wu, Ruirui; Sun, Xiance; Yang, Boyi; Wang, Yi; Xu, Yuanyuan

    2016-01-01

    Changes in profile of lipids and adipokines have been reported in patients with thyroid dysfunction. But the evidence is controversial. The present study aimed to explore the relationships between thyroid function and the profile of lipids and adipokines. A cross-sectional study was conducted in 197 newly diagnosed hypothyroid patients, 230 newly diagnosed hyperthyroid patients and 355 control subjects. Hypothyroid patients presented with significantly higher serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDLC), fasting insulin, resistin and leptin than control (p < 0.05). Hyperthyroid patients presented with significantly lower serum levels of high-density lipoprotein cholesterol, LDLC and leptin, as well as higher levels of fasting insulin, resistin, adiponectin and homeostasis model insulin resistance index (HOMA-IR) than control (p < 0.05). Nonlinear regression and multivariable linear regression models all showed significant associations of resistin or adiponectin with free thyroxine and association of leptin with thyroid-stimulating hormone (p < 0.001). Furthermore, significant correlation between resistin and HOMA-IR was observed in the patients (p < 0.001). Thus, thyroid dysfunction affects the profile of lipids and adipokines. Resistin may serve as a link between thyroid dysfunction and insulin resistance. PMID:27193069

  11. Changes in profile of lipids and adipokines in patients with newly diagnosed hypothyroidism and hyperthyroidism

    PubMed Central

    Chen, Yanyan; Wu, Xiafang; Wu, Ruirui; Sun, Xiance; Yang, Boyi; Wang, Yi; Xu, Yuanyuan

    2016-01-01

    Changes in profile of lipids and adipokines have been reported in patients with thyroid dysfunction. But the evidence is controversial. The present study aimed to explore the relationships between thyroid function and the profile of lipids and adipokines. A cross-sectional study was conducted in 197 newly diagnosed hypothyroid patients, 230 newly diagnosed hyperthyroid patients and 355 control subjects. Hypothyroid patients presented with significantly higher serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDLC), fasting insulin, resistin and leptin than control (p < 0.05). Hyperthyroid patients presented with significantly lower serum levels of high-density lipoprotein cholesterol, LDLC and leptin, as well as higher levels of fasting insulin, resistin, adiponectin and homeostasis model insulin resistance index (HOMA-IR) than control (p < 0.05). Nonlinear regression and multivariable linear regression models all showed significant associations of resistin or adiponectin with free thyroxine and association of leptin with thyroid-stimulating hormone (p < 0.001). Furthermore, significant correlation between resistin and HOMA-IR was observed in the patients (p < 0.001). Thus, thyroid dysfunction affects the profile of lipids and adipokines. Resistin may serve as a link between thyroid dysfunction and insulin resistance. PMID:27193069

  12. Maternal and Fetal Lipid and Adipokine Profiles and Their Association with Obesity.

    PubMed

    Solis-Paredes, Mario; Espino Y Sosa, Salvador; Estrada-Gutierrez, Guadalupe; Nava-Salazar, Sonia; Ortega-Castillo, Veronica; Rodriguez-Bosch, Mario; Bravo-Flores, Eyerahi; Espejel-Nuñez, Aurora; Tolentino-Dolores, Maricruz; Gaona-Estudillo, Rubí; Martinez-Bautista, Nancy; Perichart-Perera, Otilia

    2016-01-01

    Background. Maternal metabolic changes impact fetal metabolism resulting in a higher risk for developing chronic diseases later in life. The aim of this study was to assess the association between maternal and fetal adipokine and lipid profiles, as well as the influence of maternal weight on this association. Methods. Healthy pregnant women at term who delivered by C-section were enrolled. Maternal and fetal glucose, lipid profile, adiponectin, leptin, and resistin levels were analyzed by obesity and maternal weight gain. Statistics included descriptives, correlations, and mean differences (SPSS v20.0). Results. Adiponectin and resistin concentrations were higher in fetal blood, while leptin was lower (p < 0.05). A significant inverse association between maternal resistin and fetal LDL-cholesterol (LDL-C) (r = -0.327; p = 0.022) was observed. A positive correlation was found between maternal and fetal resistin (r = 0.358; p = 0.013). Women with excessive weight gain had higher leptin levels and their fetuses showed higher LDL-C levels (p < 0.05). Conclusions. Maternal resistin showed an inverse association with fetal LDL-C, suggesting that maternal adiposity status may play an active role in the regulation of fetal lipid profile and consequently, in fetal programming. Excessive maternal weight gain during pregnancy may exert an effect over metabolic mediators in both mother and newborn. PMID:27190514

  13. Maternal and Fetal Lipid and Adipokine Profiles and Their Association with Obesity

    PubMed Central

    Solis-Paredes, Mario; Espino y Sosa, Salvador; Estrada-Gutierrez, Guadalupe; Nava-Salazar, Sonia; Ortega-Castillo, Veronica; Rodriguez-Bosch, Mario; Bravo-Flores, Eyerahi; Espejel-Nuñez, Aurora; Tolentino-Dolores, Maricruz; Gaona-Estudillo, Rubí; Martinez-Bautista, Nancy; Perichart-Perera, Otilia

    2016-01-01

    Background. Maternal metabolic changes impact fetal metabolism resulting in a higher risk for developing chronic diseases later in life. The aim of this study was to assess the association between maternal and fetal adipokine and lipid profiles, as well as the influence of maternal weight on this association. Methods. Healthy pregnant women at term who delivered by C-section were enrolled. Maternal and fetal glucose, lipid profile, adiponectin, leptin, and resistin levels were analyzed by obesity and maternal weight gain. Statistics included descriptives, correlations, and mean differences (SPSS v20.0). Results. Adiponectin and resistin concentrations were higher in fetal blood, while leptin was lower (p < 0.05). A significant inverse association between maternal resistin and fetal LDL-cholesterol (LDL-C) (r = −0.327; p = 0.022) was observed. A positive correlation was found between maternal and fetal resistin (r = 0.358; p = 0.013). Women with excessive weight gain had higher leptin levels and their fetuses showed higher LDL-C levels (p < 0.05). Conclusions. Maternal resistin showed an inverse association with fetal LDL-C, suggesting that maternal adiposity status may play an active role in the regulation of fetal lipid profile and consequently, in fetal programming. Excessive maternal weight gain during pregnancy may exert an effect over metabolic mediators in both mother and newborn. PMID:27190514

  14. Leptin levels in the obese African parturient.

    PubMed

    Kafulafula, G; Moodley, J

    2001-05-01

    Prolactin, HCG and oestrogen are reported to have a role in regulating serum leptin levels and therefore adiposity in pregnancy. The aim of this study was to determine serum leptin levels during pregnancy in African women, and was conducted in the Antenatal Clinic, King Edward VIII Hospital, Durban, South Africa. Eighty-two obese and non-obese women were studied. Demographic details and anthropometric measurements were recorded, and serum leptin levels determined by radio-immunoassay in all women. Age, parity and gestational age showed a weak correlation with leptin levels. Weight (4=0.6); body mass index (r=0.5), and the circumference of midarm (r=0.4), waist (4-0.6, hip (5=0.5) and thigh correlated positively with leptin values. Serum leptin values in African pregnant women are not dissimilar to that of studies in other racial groups. PMID:12521847

  15. Association of adiponectin and metabolic syndrome in women

    PubMed Central

    Sanjari, Mojgan; Khodashahi, Mandana; Gholamhoseinian, Ahmad; Shokoohi, Mostafa

    2011-01-01

    BACKGROUND: An inverse association between serum adiponectin level and metabolic syndrome was seen in few studies. The aim of this study was to assess the association between serum adiponectin levels and metabolic syndrome in a sample of Iranian women from Kerman. METHODS: In a cross-sectional study 946 subjects were studied to determine the prevalence of metabolic syndrome and in a case control study (170 subjects for each group) the association between serum adiponectin levels and metabolic syndrome were investigated. Metabolic syndrome was defined using International Diabetes Federation (IDF) criteria. Socio-demographics factors and measures of waist circumference, blood pressure and lipid profiles were collected. Serum adiponectin level was measured by ELISA method. RESULTS: The prevalence of the metabolic syndrome was 36.7%. Mean of serum adiponectin level in individuals with metabolic syndrome was lower than individuals without it (10.5 ± 4.1 and 13.45 ± 5.6 μg/ml, respectively, p < 0.001). Low level of adiponectin was a good predictor for metabolic syndrome (a range of β coefficients out of -2.03 to -2.85 according to five models). Systolic blood pressure, body mass index (BMI) and diastolic blood pressure were independent predictors of serum adiponectin (p values were 0.001, 0.009 and 0.034, respectively). CONCLUSIONS: We found that adiponectin is negatively associated with metabolic syndrome. Systolic and diastolic blood pressure and BMI were identified as independent predictors. PMID:22973360

  16. Linkage analysis of circulating levels of adiponectin in hispanic children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adiponectin, a hormone produced exclusively by adipose tissue, is inversely associated with insulin resistance and pro-inflammatory conditions. The aim of this study was to find quantitative trait loci (QTLs) that affect circulating levels of adiponectin in Hispanic children participating in the VVA...

  17. Linkage analysis of circulating levels of adiponectin in Hispanic children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adiponectin is produced exclusively by adipose tissue and is inversely associated with insulin resistance and pro-inflammatory conditions. The aim of this study was to conduct a genome scan of circulating levels of adiponectin in Hispanic children. The present study included extended families with ...

  18. Intracerebroventricular injection of adiponectin regulates locomotor activity in rats.

    PubMed

    Miyatake, Yumiko; Shiuchi, Tetsuya; Ueta, Tomoyo; Taniguchi, Yasuko; Futami, Akari; Sato, Fukiko; Kitamura, Tadahiro; Tsutsumi, Rie; Harada, Nagakatsu; Nakaya, Yutaka; Sakaue, Hiroshi

    2015-01-01

    Enhancing exercise motivation is the best way to prevent obesity and diabetes. In this study, we examined whether adiponectin affects locomotion activity in Wister and Spontaneously-Running Tokushima-Shikoku (SPORTS) rats using two types of behavioral assays: home cage and wheel running activity. SPORTS rats were established from an original line from Wister strain that had shown high level of wheel running activity in our laboratory. Injection of adiponectin into the lateral ventricle of Wister rats and SPORTS rats decreased home cage activity, but no change was observed in the food intake and oxygen consumption. This result indicates the possibility that adiponectin can reduce non-exercise activity thermogenesis (NEAT) and physical activity via the central nervous system. In contrast, injection of adiponectin did not change wheel running activity in SPORTS rats. We produced hypothalamus-destructed model rat using monosodium glutamate (MSG) to elucidate the regulation site of adiponectin. Injection of adiponectin into MSG-treated SPORTS rats did not change amount of home cage activity and food intake, suggesting that adiponectin action on home cage activity was in the hypothalamic area. These results suggest that adiponectin regulates locomotion activity through mediobasal hypothalamus. PMID:26399348

  19. Mother and Infant Body Mass Index, Breast Milk Leptin and Their Serum Leptin Values

    PubMed Central

    Savino, Francesco; Sardo, Allegra; Rossi, Lorenza; Benetti, Stefania; Savino, Andrea; Silvestro, Leandra

    2016-01-01

    Purpose: This study investigates correlations between mother and infant Body Mass Index (BMI), their serum leptin values and breast milk leptin concentration in early infancy. Subjects and Methods: We determined serum leptin values in 58 healthy infants and leptin values in their mothers’ breast milk, using radioimmunoassay (RIA). Infant and maternal anthropometrics were measured. Results: Median leptin concentration was 3.9 ng/mL (interquartile range (IQR): 2.75) in infant serum, 4.27 ng/mL (IQR: 5.62) in maternal serum and 0.89 ng/mL (IQR: 1.32) in breast milk. Median maternal BMI and weight were 24 kg/m2 (IQR: 4.41) and 64 kg (IQR: 15). Median infant BMI was 15.80 kg/cm2 (IQR: 4.02), while average weight was 5.130 kg (IQR: 1.627). Infants serum leptin values positively correlated with infants’ BMI (p = 0.001; r = 0.213) and breast milk leptin (p = 0.03; r = 0.285). Maternal serum leptin values positively correlated with maternal BMI (p = 0.000, r = 0.449) and breast milk leptin ones (p = 0.026; r = 0.322). Conclusion: Breast milk leptin and maternal BMI could influence infant serum leptin values. Further studies are needed to better elucidate the role of genetics and environment on infant leptin production and risk of obesity later in life. PMID:27338468

  20. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism

    PubMed Central

    Park, Hyeong-Kyu; Ahima, Rexford S.

    2014-01-01

    Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. However, further research on molecular mediators of leptin resistance is needed for the development of targeted leptin sensitizing therapies for obesity and related metabolic diseases. PMID:25199978

  1. Differential neutrophil responses to bacterial stimuli: Streptococcal strains are potent inducers of heparin-binding protein and resistin-release

    PubMed Central

    Snäll, Johanna; Linnér, Anna; Uhlmann, Julia; Siemens, Nikolai; Ibold, Heike; Janos, Marton; Linder, Adam; Kreikemeyer, Bernd; Herwald, Heiko; Johansson, Linda; Norrby-Teglund, Anna

    2016-01-01

    Neutrophils are critical for the control of bacterial infections, but they may also contribute to disease pathology. Here we explore neutrophil responses, in particular the release of sepsis-associated factors heparin-binding protein (HBP) and resistin in relation to specific bacterial stimuli and sepsis of varying aetiology. Analyses of HBP and resistin in plasma of septic patients revealed elevated levels as compared to non-infected critically ill patients. HBP and resistin correlated significantly in septic patients, with the strongest association seen in group A streptococcal (GAS) cases. In vitro stimulation of human neutrophils revealed that fixed streptococcal strains induced significantly higher release of HBP and resistin, as compared to Staphylococcus aureus or Escherichia coli. Similarly, neutrophils stimulated with the streptococcal M1-protein showed a significant increase in co-localization of HBP and resistin positive granules as well as exocytosis of these factors, as compared to LPS. Using a GAS strain deficient in M1-protein expression had negligible effect on neutrophil activation, while a strain deficient in the stand-alone regulator MsmR was significantly less stimulatory as compared to its wild type strain. Taken together, the findings suggest that the streptococcal activation of neutrophils is multifactorial and involves, but is not limited to, proteins encoded by the FCT-locus. PMID:26887258

  2. Adipocyte iron regulates leptin and food intake

    PubMed Central

    Gao, Yan; Li, Zhonggang; Gabrielsen, J. Scott; Simcox, Judith A.; Lee, Soh-hyun; Jones, Deborah; Cooksey, Bob; Stoddard, Gregory; Cefalu, William T.; McClain, Donald A.

    2015-01-01

    Dietary iron supplementation is associated with increased appetite. Here, we investigated the effect of iron on the hormone leptin, which regulates food intake and energy homeostasis. Serum ferritin was negatively associated with serum leptin in a cohort of patients with metabolic syndrome. Moreover, the same inverse correlation was observed in mice fed a high-iron diet. Adipocyte-specific loss of the iron exporter ferroportin resulted in iron loading and decreased leptin, while decreased levels of hepcidin in a murine hereditary hemochromatosis (HH) model increased adipocyte ferroportin expression, decreased adipocyte iron, and increased leptin. Treatment of 3T3-L1 adipocytes with iron decreased leptin mRNA in a dose-dependent manner. We found that iron negatively regulates leptin transcription via cAMP-responsive element binding protein activation (CREB activation) and identified 2 potential CREB-binding sites in the mouse leptin promoter region. Mutation of both sites completely blocked the effect of iron on promoter activity. ChIP analysis revealed that binding of phosphorylated CREB is enriched at these two sites in iron-treated 3T3-L1 adipocytes compared with untreated cells. Consistent with the changes in leptin, dietary iron content was also directly related to food intake, independently of weight. These findings indicate that levels of dietary iron play an important role in regulation of appetite and metabolism through CREB-dependent modulation of leptin expression. PMID:26301810

  3. Leptin potentiates astrogenesis in the developing hypothalamus

    PubMed Central

    Rottkamp, Daniele M.; Rudenko, Ivan A.; Maier, Matthew T.; Roshanbin, Sahar; Yulyaningsih, Ernie; Perez, Luz; Valdearcos, Martin; Chua, Streamson; Koliwad, Suneil K.; Xu, Allison W.

    2015-01-01

    Background The proper establishment of hypothalamic feeding circuits during early development has a profound influence on energy homeostasis, and perturbing this process could predispose individuals to obesity and its associated consequences later in life. The maturation of hypothalamic neuronal circuitry in rodents takes place during the initial postnatal weeks, and this coincides with a dramatic surge in the circulating level of leptin, which is known to regulate the outgrowth of key neuronal projections in the maturing hypothalamus. Coincidently, this early postnatal period also marks the rapid proliferation and expansion of astrocytes in the brain. Methods Here we examined the effects of leptin on the proliferative capacity of astrocytes in the developing hypothalamus by treating postnatal mice with leptin. Mutant mice were also generated to conditionally remove leptin receptors from glial fibrillary acidic protein (GFAP)-expressing cells in the postnatal period. Results and conclusions We show that GFAP-expressing cells in the periventricular zone of the 3rd ventricle were responsive to leptin during the initial postnatal week. Leptin enhanced the proliferation of astrocytes in the postnatal hypothalamus and conditional removal of leptin receptors from GFAP-expressing cells during early postnatal period limited astrocyte proliferation. While increasing evidence demonstrates a direct role of leptin in regulating astrocytes in the adult brain, and given the essential function of astrocytes in modulating neuronal function and connectivity, our study indicates that leptin may exert its metabolic effects, in part, by promoting hypothalamic astrogenesis during early postnatal development. PMID:26629411

  4. Connecting leptin signaling to biological function

    PubMed Central

    Allison, Margaret B.; Myers, Martin G.

    2014-01-01

    Hypothalamic leptin action promotes negative energy balance and modulates glucose homeostasis, as well as serving as a permissive signal to the neuroendocrine axes that control growth and reproduction. Since the initial discovery of leptin 20 years ago, we have learned a great deal about the molecular mechanisms of leptin action. An important aspect of this has been the dissection of the cellular mechanisms of leptin signaling, and how specific leptin signals influence physiology. Leptin acts via the long form of the leptin receptor, LepRb. LepRb activation and subsequent tyrosine phosphorylation recruits and activates multiple signaling pathways, including STAT transcription factors, SHP2 and ERK signaling, the IRS-protein/PI3Kinase pathway, and SH2B1. Each of these pathways controls specific aspects of leptin action and physiology. Important inhibitory pathways mediated by suppressor of cytokine signaling (SOCS) proteins and protein tyrosine phosphatases (PTPases) also limit physiologic leptin action. This review summarizes the signaling pathways engaged by LepRb and their effects on energy balance, glucose homeostasis, and reproduction. Particular emphasis is given to the multiple mouse models which have been used to elucidate these functions in vivo. PMID:25232147

  5. Adipocyte iron regulates leptin and food intake.

    PubMed

    Gao, Yan; Li, Zhonggang; Gabrielsen, J Scott; Simcox, Judith A; Lee, Soh-hyun; Jones, Deborah; Cooksey, Bob; Stoddard, Gregory; Cefalu, William T; McClain, Donald A

    2015-09-01

    Dietary iron supplementation is associated with increased appetite. Here, we investigated the effect of iron on the hormone leptin, which regulates food intake and energy homeostasis. Serum ferritin was negatively associated with serum leptin in a cohort of patients with metabolic syndrome. Moreover, the same inverse correlation was observed in mice fed a high-iron diet. Adipocyte-specific loss of the iron exporter ferroportin resulted in iron loading and decreased leptin, while decreased levels of hepcidin in a murine hereditary hemochromatosis (HH) model increased adipocyte ferroportin expression, decreased adipocyte iron, and increased leptin. Treatment of 3T3-L1 adipocytes with iron decreased leptin mRNA in a dose-dependent manner. We found that iron negatively regulates leptin transcription via cAMP-responsive element binding protein activation (CREB activation) and identified 2 potential CREB-binding sites in the mouse leptin promoter region. Mutation of both sites completely blocked the effect of iron on promoter activity. ChIP analysis revealed that binding of phosphorylated CREB is enriched at these two sites in iron-treated 3T3-L1 adipocytes compared with untreated cells. Consistent with the changes in leptin, dietary iron content was also directly related to food intake, independently of weight. These findings indicate that levels of dietary iron play an important role in regulation of appetite and metabolism through CREB-dependent modulation of leptin expression. PMID:26301810

  6. Leptin signalling pathways in hypothalamic neurons.

    PubMed

    Kwon, Obin; Kim, Ki Woo; Kim, Min-Seon

    2016-04-01

    Leptin is the most critical hormone in the homeostatic regulation of energy balance among those so far discovered. Leptin primarily acts on the neurons of the mediobasal part of hypothalamus to regulate food intake, thermogenesis, and the blood glucose level. In the hypothalamic neurons, leptin binding to the long form leptin receptors on the plasma membrane initiates multiple signaling cascades. The signaling pathways known to mediate the actions of leptin include JAK-STAT signaling, PI3K-Akt-FoxO1 signaling, SHP2-ERK signaling, AMPK signaling, and mTOR-S6K signaling. Recent evidence suggests that leptin signaling in hypothalamic neurons is also linked to primary cilia function. On the other hand, signaling molecules/pathways mitigating leptin actions in hypothalamic neurons have been extensively investigated in an effort to treat leptin resistance observed in obesity. These include SOCS3, tyrosine phosphatase PTP1B, and inflammatory signaling pathways such as IKK-NFκB and JNK signaling, and ER stress-mitochondrial signaling. In this review, we discuss leptin signaling pathways in the hypothalamus, with a particular focus on the most recently discovered pathways. PMID:26786898

  7. Enhanced adiponectin actions by overexpression of adiponectin receptor 1 in macrophages

    PubMed Central

    Luo, Nanlan; Chung, B Hong; Wang, Xiangdong; Klein, Richard L.; Tang, Chao-Ke; Garvey, W. Timothy; Fu, Yuchang

    2013-01-01

    Objective Adiponectin is one of several important, metabolically active cytokines secreted from adipose tissue. Epidemiologic studies have associated low circulating levels of this adipokine with multiple metabolic disorders including obesity, insulin resistance, type II diabetes, and cardiovascular disease. To investigate how enhanced adiponectin-mediated changes in metabolism in vivo, we generated transgenic mice which specifically overexpress the gene coding for adiponectin receptor 1 (AdipoR1) in mouse macrophages using the human scavenger receptor A-I gene (SR-AI) enhancer/promoter. We found that macrophage-specific AdipoR1 transgenic mice (AdR1-TG) presented reduced whole body weight, fat accumulation and liver steatosis when these transgenic mice were fed with a high fat diet. Moreover, these macrophage AdR1-TG mice exhibited enhanced whole-body glucose tolerance and insulin sensitivity with reduced proinflammatory cytokines, MCP-1 and TNF-α, both in the serum and in the insulin target metabolic tissues. Additional studies demonstrated that these macrophage AdR1-TG animals exhibited reduced macrophage foam cell formation in the arterial wall when these transgenic mice were crossed with a low-density lipoprotein receptor (Ldlr) deficient mouse model. Conclusions These results suggest that AdipoR1 overexpressed in macrophages can physiologically modulate metabolic activities in vivo by enhancing adiponectin actions in distal metabolically active tissues. The AdipoR1 modified macrophages provide unique interactions with the residented tissues/cells, suggesting a novel role of macrophage adiponectin receptor in improving metabolic disorders in vivo. PMID:23510830

  8. Phenotypic and genetic variation in leptin as determinants of weight regain

    PubMed Central

    Rudich, A; Meiner, V; Schwarzfuchs, D; Sharon, N; Shpitzen, S; Blüher, M; Stumvoll, M; Thiery, J; Fiedler, GM; Friedlander, Y; Leiterstdorf, E; Shai, I

    2016-01-01

    Aims Over 75% of obese subjects fail to maintain their weight following weight loss interventions. We aimed to identify phenotypic and genetic markers associated with weight maintenance/regain following a dietary intervention. Subjects and methods In the 2-year Dietary Intervention Randomized Controlled Trial, we assessed potential predictors for weight changes during the ‘weight loss phase’ (0–6 months) and the ‘weight maintenance/regain phase’ (7–24 months). Genetic variation between study participants was studied using single-nucleotide polymorphisms in the leptin gene (LEP). Results Mean weight reduction was −5.5% after 6 months, with a mean weight regain of 1.2% of baseline weight during the subsequent 7–24 months. In a multivariate regression model, higher baseline high-molecular-weight adiponectin was the only biomarker predictor of greater success in 0- to 6-month weight loss (β = −0.222, P-value = 0.044). In a multivariate regression model adjusted for 6-month changes in weight and various biomarkers, 6-month plasma leptin reduction exhibited the strongest positive association with 6-month weight loss (β = 0.505, P-value<0.001). Conversely, 6-month plasma leptin reduction independently predicted weight regain during the following 18 months (β = −0.131, P-value<.013). Weight regain was higher among participants who had a greater (top tertiles) 6-month decrease in both weight and leptin (+ 3.4% (95% confidence interval 2.1–4.8)) as compared with those in the lowest combined tertiles (+ 0.2% (95% confidence interval −1.1 to 1.4)); P-value<0.001. Weight regain was further significantly and independently associated with genetic variations in LEP (P = 0.006 for both rs4731426 and rs2071045). Adding genetic data to the phenotypic multivariate model increased its predictive value for weight regain by 34%. Conclusion Although greater reduction in leptin concentrations during the initial phase of a dietary intervention is associated with

  9. Adiponectin and the control of female reproductive functions.

    PubMed

    Palin, Marie-France; Bordignon, V Vilceu; Murphy, Bruce D

    2012-01-01

    Adiponectin is the most abundant protein secreted by the white adipose tissue. It circulates at high levels in the bloodstream and its serum concentration is inversely correlated with body fat mass. The wide distribution of adiponectin receptors (AdipoR1, AdipoR2, and T-cadherin) in peripheral tissues and organs allows adiponectin to exert pleiotropic effects on whole-body metabolism. Besides its well-known antidiabetic, antiatherogenic, and anti-inflammatory properties, accumulating evidence suggests a direct role for adiponectin in reproductive tissues. The mammalian ovary and the ovarian follicle express AdipoR1 and AdipoR2, and treating pig granulosa cells with adiponectin induces changes characteristic of the periovulatory period. Moreover, additive effects are observed between adiponectin and insulin in induction of granulosa cell gene expression, thus suggesting that adiponectin actions on the ovary may be mediated through its insulin-sensitizing effects. Adiponectin receptors are also detected in the uterus. In women, higher AdipoR1 and AdipoR2 gene expression was observed during the mid-secretory phase of the menstrual cycle, suggesting that adiponectin is implicated in the endometrial changes in preparation for embryo implantation. Adiponectin receptors are found in oocytes and early developing pig, rabbit, and mice embryos, and it has been demonstrated that adiponectin can increase the success of porcine embryo development to the blastocyst stage in vitro. Moreover, adiponectin concentration is two to three times greater in human fetal circulation and in umbilical cord blood, compared to adult plasma. This further indicates a role for adiponectin in fetal growth. It has been further suggested that adipose-derived and locally produced adiponectin may act as a key neuromodulator of reproductive functions. For example, the inhibition of LH and GnRH release from rat pituitary and hypothalamic cells following treatment with adiponectin provides evidence that

  10. Long-term angiotensin II AT1 receptor inhibition produces adipose tissue hypotrophy accompanied by increased expression of adiponectin and PPARgamma.

    PubMed

    Zorad, Stefan; Dou, Jing-tao; Benicky, Julius; Hutanu, Daniel; Tybitanclova, Katarina; Zhou, Jin; Saavedra, Juan M

    2006-12-15

    To clarify the mechanism of the effects of angiotensin II AT(1) receptor antagonists on adipose tissue, we treated 8 week-old male Wistar Kyoto rats with the angiotensin II AT(1) receptor antagonist Candesartan cilexetil (10 mg/kg/day) for 18 weeks. Candesartan cilexetil reduced body weight gain, decreased fat tissue mass due to hypotrophy of epididymal and retroperitoneal adipose tissue and decreased adipocyte size without changing the number of adipocytes. Candesartan cilexetil decreased serum leptin levels and epididymal leptin mRNA, increased serum adiponectin levels and epididymal adiponectin mRNA, decreased epididymal tumor necrosis factor alpha (TNFalpha) mRNA, and increased fatty acid synthase mRNA. Considered free of peroxisome proliferator-activated receptor gamma (PPARgamma) agonist activity, Candesartan cilexetil increased epididymal expression of PPARgamma mRNA. The effects of Candesartan cilexetil on adipokine production and release may be attributable to PPARgamma activation and/or decrease in adipocyte cell size. In addition, Candesartan cilexetil treatment increased the expression of epididymal angiotensin II AT(2) receptor mRNA and protein and decreased the expression of renin receptor mRNA. These results suggest that Candesartan cilexetil influences lipid metabolism in adipose tissue by promoting adipose tissue rearrangement and modulating adipokine expression and release. These effects are probably consequences of local angiotensin II AT(1) receptor inhibition, angiotensin II AT(2) receptor stimulation, and perhaps additional angiotensin II-independent mechanisms. Our results indicate that the activity of local renin-angiotensin system plays an important role in adipose tissue metabolism. The decrease in the pro-inflammatory cytokine TNFalpha and the increase in the anti-inflammatory adipokine adiponectin indicate that Candesartan cilexetil may exert significant anti-inflammatory properties. PMID:17064684

  11. Underactivation of the adiponectin-adiponectin receptor 1 axis in clear cell renal cell carcinoma: implications for progression.

    PubMed

    Kleinmann, Nir; Duivenvoorden, Wilhelmina C M; Hopmans, Sarah N; Beatty, Laura K; Qiao, Shengjun; Gallino, Daniel; Lhotak, Sarka; Daya, Dean; Paschos, Athanasios; Austin, Richard C; Pinthus, Jehonathan H

    2014-02-01

    Energy-sensing pathways, normally coordinated by 5' AMP-activated protein kinase (AMPK), are dysregulated in renal cell carcinoma (RCC). Obesity can accentuate the pre-existing pro-tumorigenic metabolic machinery in RCC cells through its associated obesogenic hormonal milieu, characterized by lower circulating levels of adiponectin. In RCC patients, low adiponectin levels associate clinically with more aggressive disease. We investigated the adiponectin signaling pathway in RCC, focusing on adiponectin receptor 1 (AdipoR1) and associated activation of AMPK. AdipoR1 protein in RCC and normal surrounding renal tissues was determined by Western blot analysis and immunohistochemistry. Anti-tumorigenic effects of adiponectin in RCC cells in vitro were investigated via VEGF and MMP ELISA and invasion assays. Using in vivo models of RCC, the effect of AdipoR1-knockdown (shRNA) on tumor latency, growth and dissemination were determined. AdipoR1 protein was significantly reduced in clear cell RCC specimens. Adiponectin treatment inhibited VEGF, MMP-2 and MMP-9 secretion and activity and invasive and migratory capacities of RCC cells. AMPKα1-knockdown (shRNA) attenuated adiponectin's effects. In cells stably expressing AdipoR1-specific shRNA, AMPK activation by adiponectin was significantly reduced compared to cells expressing control shRNA. In vivo, AdipoR1 knockdown increased the growth, dissemination and angiogenesis of RCC. These findings suggest that deficiencies in the entire adiponectin hormonal axis (the hormone and its receptor) result in underactivation of AMPK leading to increased angiogenic and invasive capacities of RCC. The established link between obesity and RCC can therefore be further explained by the adiponectin deficiency in obese individuals together with reduced AdipoR1 protein in RCC. PMID:24096711

  12. Differentiation of human adipocytes at physiological oxygen levels results in increased adiponectin secretion and isoproterenol-stimulated lipolysis

    PubMed Central

    Famulla, Susanne; Schlich, Raphaela; Sell, Henrike; Eckel, Jürgen

    2012-01-01

    Adipose tissue (AT) hypoxia occurs in obese humans and mice. Acute hypoxia in adipocytes causes dysregulation of adipokine secretion with an increase in inflammatory factors and diminished adiponectin release. O2 levels in humans range between 3 and 11% revealing that conventional in vitro culturing at ambient air and acute hypoxia treatment (1% O2) are performed under non-physiological conditions. In this study, we mimicked physiological conditions by differentiating human primary adipocytes under 10% or 5% O2 in comparison to 21% O2. Induction of differentiation markers was comparable between all three conditions. Adipokine release by adipocytes differentiated at lower oxygen levels was altered, with a marked upregulation of adiponectin, IL-6 and DPP4 secretion, and reduced leptin levels compared with adipocytes differentiated at 21% O2. Isoproterenol-induced lipolysis was significantly elevated in adipocytes differentiated at 10% and 5% compared with 21% O2. This effect was accompanied by increased protein expression of β-1 and -2 adrenergic receptor, HSL and perilipin. Conditioned medium (CM) of adipocytes differentiated at the three different conditions was generated for stimulation of human skeletal muscle cells (SkMC) or smooth muscle cells (SMC). CM-induced insulin resistance in SkMC was comparable for the different CMs. However, the SMC proliferative effect of CM from adipocytes differentiated at 10% O2 was significantly reduced compared with 21% O2. This study demonstrates that oxygen levels during adipogenesis are important factors altering adipocyte functionality such as adipokine release, in particular adiponectin secretion, as well as the hormone-induced lipolytic pathway. PMID:23700522

  13. Serum Vaspin Levels Are Associated with the Development of Clinically Manifest Arthritis in Autoantibody-Positive Individuals

    PubMed Central

    Maijer, Karen I.; Neumann, Elena; Müller-Ladner, Ulf; Drop, Daniël A. C. A. D.; Ramwadhdoebe, Tamara H.; Choi, Ivy Y. K.; Gerlag, Daniëlle M.; de Hair, Maria J. H.; Tak, Paul P.

    2015-01-01

    Objectives We have previously shown that overweight may increase the risk of developing rheumatoid arthritis (RA) in autoantibody positive individuals. Adipose tissue could contribute to the development of RA by production of various bioactive peptides. Therefore, we examined levels of adipokines in serum and synovial tissue of subjects at risk of RA. Methods Fifty-one individuals positive for immunoglobulin M rheumatoid factor (IgM-RF) and/or anti-citrullinated protein antibodies (ACPA), without arthritis, were included in this prospective study. Levels of adiponectin, vaspin, resistin, leptin, chemerin and omentin were determined in baseline fasting serum samples (n = 27). Synovial tissue was obtained by arthroscopy at baseline and we examined the expression of adiponectin, resistin and visfatin by immunohistochemistry. Results The development of clinically manifest arthritis after follow-up was associated with baseline serum vaspin levels (HR1.5 (95% CI 1.1 to 2.2); p = 0.020), also after adjustment for overweight (HR1.7 (95% CI 1.1 to 2.5); p = 0.016). This association was not seen for other adipokines. Various serum adipokine levels correlated with BMI (adiponectin r = -0.538, leptin r = 0.664; chemerin r = 0.529) and systemic markers of inflammation such as CRP levels at baseline (adiponectin r = -0.449, omentin r = -0.557, leptin r = 0.635, chemerin r = 0.619, resistin r = 0.520) and ESR (leptin r = 0.512, chemerin r = 0.708), p-value<0.05. Synovial expression of adiponectin, resistin and visfatin was not associated with development of clinically manifest arthritis. Conclusions In this exploratory study, serum adipokines were associated with an increased inflammatory state in autoantibody-positive individuals at risk of developing RA. Furthermore, serum vaspin levels may assist in predicting the development of arthritis in these individuals. PMID:26670468

  14. Expression of leptin and leptin receptor isoforms in the rat and human carotid body.

    PubMed

    Porzionato, Andrea; Rucinski, Marcin; Macchi, Veronica; Stecco, Carla; Castagliuolo, Ignazio; Malendowicz, Ludwik K; De Caro, Raffaele

    2011-04-18

    Leptin is known to play a role in the modulation of metabolism and control of breathing acting mainly on central nervous structures, although additional actions on peripheral arterial chemoreceptors have also been suggested in the literature. We therefore examined by means of immunohistochemistry the expression of leptin and leptin receptors in the carotid bodies of rats and humans. Leptin expression and relative expression of leptin receptor isoforms were also studied in rats by real-time PCR. No leptin or leptin receptor immunoreactivities were visible in the type II cells of either series. In rat carotid bodies, diffuse positive stainings for leptin and leptin receptors (both with antibody recognizing all receptor isoforms and antibody specific for Ob-Rb) were observed in type I cells. In human carotid bodies, the mean percentage (±standard error) of leptin immunoreactive type I cells was 39.4%±5.1% and the percentages of leptin receptor immunoreactive type I cells were 57.3%±3.9% with antibody recognizing all receptor isoforms and 33.3%±4.2% with antibody specific for isoform Ob-Rb. Double immunofluorescences with anti-tyrosine hydroxylase (type I cell marker) and anti-glial fibrillary acidic protein (type II cell markers) confirmed the selective location of leptin and Ob-Rb in type I cells. Real-time PCR showed the expression of leptin and Ob-Ra, Ob-Rb, Ob-Rc and Ob-Rf isoform mRNA in the rat carotid body, levels of expression being Ob-Rf>Ob-Rc>Ob-Ra>Ob-Rb. Ob-Re mRNA was not detected. The above findings suggest a role of circulating or locally produced leptin in the regulation of chemoreceptor discharge and/or metabolic sensing function, by means of direct action on type I cells. PMID:21334312

  15. 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

  16. Regulation and Role of Leptin: Poultry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The recently discovered protein, leptin, which is secreted by fat cells, has been implicated in the regulation of appetite, energy balance, and the neuroendocrine axis in poultry. The leptin receptor has been cloned and is a member of the class I cytokine family of receptors is found in the brain a...

  17. The Effects of Leptin on Breastfeeding Behaviour.

    PubMed

    Cannon, Anna M; Kakulas, Foteini; Hepworth, Anna R; Lai, Ching Tat; Hartmann, Peter E; Geddes, Donna T

    2015-10-01

    Breastfed infants have a reduced risk of becoming overweight and/or obese later in life. This protective effect has been partly attributed to leptin present in breastmilk. This study investigated 24-h variations of skim milk leptin and its relationship with breastmilk macronutrients and infant breastfeeding patterns. Exclusive breastfeeding mothers of term singletons (n = 19; age 10 ± 5 weeks) collected pre- and post-feed breastmilk samples for every breastfeed over a 24-h period and test-weighed their infants to determine milk intake at every breastfeed over a 24-h period. Samples (n = 454) were analysed for leptin, protein, lactose and fat content. Skim milk leptin concentration did not change with feeding (p = 0.184). However, larger feed volumes (>105 g) were associated with a decrease in post-feed leptin levels (p = 0.009). There was no relationship between the change in leptin levels and change in protein (p = 0.313) or lactose levels (p = 0.587) between pre- and post-feed milk, but there was a trend for a positive association with changes in milk fat content (p = 0.056). Leptin concentration significantly increased at night (p < 0.001) indicating a possible 24-h pattern. Leptin dose (ng) was not associated with the time between feeds (p = 0.232). Further research should include analysis of whole breastmilk and other breastmilk fractions to extend these findings. PMID:26437426

  18. Thyroid Hormone and Leptin in the Testis

    PubMed Central

    Ramos, Cristiane Fonte; Zamoner, Ariane

    2014-01-01

    Leptin is primarily expressed in white adipose tissue; however, it is expressed in the hypothalamus and reproductive tissues as well. Leptin acts by activating the leptin receptors (Ob-Rs). Additionally, the regulation of several neuroendocrine and reproductive functions, including the inhibition of glucocorticoids and enhancement of thyroxine and sex hormone concentrations in human beings and mice are leptin functions. It has been suggested that thyroid hormones (TH) could directly regulate leptin expression. Additionally, hypothyroidism compromises the intracellular integration of leptin signaling specifically in the arcuate nucleus. Two TH receptor isoforms are expressed in the testis, TRa and TRb, with TRa being the predominant one that is present in all stages of development. The effects of TH involve the proliferation and differentiation of Sertoli and Leydig cells during development, spermatogenesis, and steroidogenesis. In this context, TH disorders are associated with sexual dysfunction. An endocrine and/or direct paracrine effect of leptin on the gonads inhibits testosterone production in Leydig cells. Further studies are necessary to clarify the effects of both hormones in the testis during hypothyroidism. The goal of this review is to highlight the current knowledge regarding leptin and TH in the testis. PMID:25505448

  19. Role of Adiponectin in Coronary Heart Disease Risk

    PubMed Central

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

    2016-01-01

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

  20. Autocrine effects of transgenic resistin reduce palmitate and glucose oxidation in brown adipose tissue.

    PubMed

    Pravenec, Michal; Mlejnek, Petr; Zídek, Václav; Landa, Vladimír; Šimáková, Miroslava; Šilhavý, Jan; Strnad, Hynek; Eigner, Sebastian; Eigner Henke, Kateřina; Škop, Vojtěch; Malínská, Hana; Trnovská, Jaroslava; Kazdová, Ludmila; Drahota, Zdeněk; Mráček, Tomáš; Houštěk, Josef

    2016-06-01

    Resistin has been originally identified as an adipokine that links obesity to insulin resistance in mice. In our previous studies in spontaneously hypertensive rats (SHR) expressing a nonsecreted form of mouse resistin (Retn) transgene specifically in adipose tissue (SHR-Retn), we have observed an increased lipolysis and serum free fatty acids, ectopic fat accumulation in muscles, and insulin resistance. Recently, brown adipose tissue (BAT) has been suggested to play an important role in the pathogenesis of metabolic disturbances. In the current study, we have analyzed autocrine effects of transgenic resistin on BAT glucose and lipid metabolism and mitochondrial function in the SHR-Retn vs. nontransgenic SHR controls. We observed that interscapular BAT isolated from SHR-Retn transgenic rats compared with SHR controls showed a lower relative weight (0.71 ± 0.05 vs. 0.91 ± 0.08 g/100 g body wt, P < 0.05), significantly reduced both basal and insulin stimulated incorporation of palmitate into BAT lipids (658 ± 50 vs. 856 ± 45 and 864 ± 47 vs. 1,086 ± 35 nmol/g/2 h, P ≤ 0.01, respectively), and significantly decreased palmitate oxidation (37.6 ± 4.5 vs. 57 ± 4.1 nmol/g/2 h, P = 0.007) and glucose oxidation (277 ± 34 vs. 458 ± 38 nmol/g/2 h, P = 0.001). In addition, in vivo microPET imaging revealed significantly reduced (18)F-FDG uptake in BAT induced by exposure to cold in SHR-Retn vs. control SHR (232 ± 19 vs. 334 ± 22 kBq/ml, P < 0.05). Gene expression profiles in BAT identified differentially expressed genes involved in skeletal muscle and connective tissue development, inflammation and MAPK and insulin signaling. These results provide evidence that autocrine effects of resistin attenuate differentiation and activity of BAT and thus may play a role in the pathogenesis of insulin resistance in the rat. PMID:27113533

  1. Leptin and cancer: Pathogenesis and modulation

    PubMed Central

    Dutta, Deep; Ghosh, Sujoy; Pandit, Kaushik; Mukhopadhyay, Pradip; Chowdhury, Subhankar

    2012-01-01

    Leptin, a product of Ob gene from adipocytes regulates appetite, energy expenditure and body mass composition by decreasing orexigenic and increasing anorexigenic neuropeptide release from hypothalamus. Research over the past few years have suggested leptin/leptin receptor dysregulation to have a role in the development of a large variety of malignancies like breast ca, thyroid ca, endometrial ca and gastrointestinal malignancies, predominantly through JAK/STAT pathway which modulates PI3K/AKT3 signaling, ERK1/2 signaling, expression of antiapoptotic proteins (like XIAP), systemic inflammation (TNF-α, IL6), angiogenic factors (VEGF) and hypoxia inducible factor-1a (HIF-1a) expression. In this review, the current understanding of leptin's role in carcinogenesis has been elaborated. Also a few agents modulating leptin signaling to inhibit cancer cell growth has been described. PMID:23565495

  2. [Leptin and hypothalamus-hypophysis-thyroid axis].

    PubMed

    Riccioni, G; Menna, V; Lambo, M S; Della Vecchia, R; Di Ilio, C; De Lorenzo, A; D'Orazio, N

    2004-01-01

    The leptin system is a major regulator of food intake and metabolic rate. The leptin, an adipose tissue hormone whose plasma levels reflect energy stores, plays an important rule in the pathogenesis of such eating disorders like bulimia and anorexia. Thyroid hormones are major regulators of energy homeostasis. It is possible that leptin and thyroid hormone exert their actions on thermogenesis and energy metabolism via the same common effector patways. Leptin influences feedback regulation of the hypotalamic TRH-secreting neurons by thyroid hormone. Low serum levels of thyroid hormones reflect a dysfunction of the hypotalamic-pituitary-thyroid (HPT) and hypotalamic-pituitary-adrenal (HPA) axis in patients with nervosa anorexia. Neuroendocrine effects of leptin include effects on the HPT and HPA axis. The aim of this work is to evaluated the interactions between leptina and HPT axis on the basis of recent published works and reviews in literature. PMID:15147079

  3. Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation.

    PubMed

    Deshmukh, Sachin K; Srivastava, Sanjeev K; Bhardwaj, Arun; Singh, Ajay P; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L; Dal Zotto, Valeria; Carter, James E; Singh, Seema

    2015-05-10

    African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity. PMID:25868978

  4. Beneficial effect of combination therapy using an angiotensin-converting enzyme inhibitor plus verapamil on circulating resistin levels in hypertensive patients with type 2 diabetes

    PubMed Central

    Rubio-Guerra, Alberto F; Vargas-Robles, Hilda; Lozano Nuevo, Jose J; Elizalde-Barrera, Cesar I; Huerta-Ramirez, Saul; Escalante-Acosta, Bruno A

    2012-01-01

    BACKGROUND: Resistin levels are strongly correlated with insulin resistance and vascular inflammation. Type 2 diabetic and hypertensive patients have higher circulating levels of resistin, which is associated with endothelial dysfunction. OBJECTIVE: To compare the effect of trandolapril (T) and its fixed-dose combination with verapamil (FDTV) on resistin levels in hypertensive, type-2 diabetic patients. METHODS: Forty type-2 diabetic patients with never-treated hypertension were randomly assigned to two groups. One group received FDTV 2 mg/180 mg once per day; the other group received T 2 mg once per day. Study drugs were administered for three months in both groups. Resistin levels were measured using ELISA at the beginning of the study and at study end. Patients were evaluated monthly for blood pressure, fasting serum glucose levels and adverse events. Statistical analysis was performed using ANOVA. RESULTS: All patients experienced a significant reduction in blood pressure. Both therapeutic regimens reduced resistin levels; however, FDTV treatment resulted in a greater decrease in resistin levels (mean [± SD] 25.5±13 ng/mL to 17.2±10 ng/mL) when compared with T treatment (22.4±12 ng/mL to 18.5±8 ng/mL) (P<0.05). None of the patients experienced an adverse event. CONCLUSION: Results showed that FDTV resulted in a greater reduction in resistin levels than T treatment alone. PMID:23592936

  5. Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation

    PubMed Central

    Bhardwaj, Arun; Singh, Ajay P.; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L.; Zotto, Valeria Dal; Carter, James E.; Singh, Seema

    2015-01-01

    African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity. PMID:25868978

  6. 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...

  7. Adiponectin: an adipokine with protective features against metabolic syndrome

    PubMed Central

    Esfahani, Maryam; Movahedian, Ahmad; Baranchi, Mostafa; Goodarzi, Mohammad Taghi

    2015-01-01

    Metabolic syndrome (MetS) as a collection of obesity-associated disorders is associated with inflammation, oxidative stress, pro-thrombotic state, elevated risk of developing cardiovascular disease and type 2 diabetes. Adiponectin is one of the most abundant peptide hormones derived from adipose tissue. This protein plays a major role in glucose and lipid metabolism and prevents development of vascular changes. Anti-oxidative and anti-inflammatory effects are the other features of adiponectin. Hypoadiponectinemia is associated with hypertension and pro-thrombotic state. In this review, we discuss the crucial role of adiponectin in prevention of metabolic syndrome considering its effects on the components of this syndrome. Pharmacological interventions and lifestyle modification may increase plasma adiponectin level or tissue sensitivity which seems to be a promising target for prevention and therapeutic approaches of MetS and related diseases. PMID:26124928

  8. Adiponectin, driver or passenger on the road to insulin sensitivity?

    PubMed Central

    Ye, Risheng; Scherer, Philipp E.

    2013-01-01

    Almost 20 years have passed since the first laboratory evidence emerged that an abundant message encoding a protein with homology to the C1q superfamily is highly specifically expressed in adipocytes. At this stage, we refer to this protein as adiponectin. Despite more than 10,000 reports in the literature since its initial description, we seem to have written only the first chapter in the textbook on adiponectin physiology. With every new aspect we learn about adiponectin, a host of new questions arise with respect to the underlying molecular mechanisms. Here, we aim to summarize recent findings in the field and bring the rodent studies that suggest a causal relationship between adiponectin levels in plasma and systemic insulin sensitivity in perspective with the currently available data on the clinical side. PMID:24049728

  9. Resistin-Like Molecule-β in Scleroderma-Associated Pulmonary Hypertension

    PubMed Central

    Angelini, Daniel J.; Su, Qingning; Yamaji-Kegan, Kazuyo; Fan, Chunling; Teng, Xingwu; Hassoun, Paul M.; Yang, Stephen C.; Champion, Hunter C.; Tuder, Rubin M.; Johns, Roger A.

    2009-01-01

    Scleroderma is a systemic, mixed connective tissue disease that can impact the lungs through pulmonary fibrosis, vascular remodeling, and the development of pulmonary hypertension and right heart failure. Currently, little is known about the molecular mechanisms that drive this condition, but we have recently identified a novel gene product that is up-regulated in a murine model of hypoxia-induced pulmonary hypertension. This molecule, known as hypoxia-induced mitogenic factor (HIMF), is a member of the newly described resistin gene family. We have demonstrated that HIMF has mitogenic, angiogenic, vasoconstrictive, inflammatory, and chemokine-like properties, all of which are associated with vascular remodeling in the lung. Here, we demonstrate that the human homolog of HIMF, resistin-like molecule (RELM)-β, is expressed in the lung tissue of patients with scleroderma-associated pulmonary hypertension and is up-regulated compared with normal control subjects. Immunofluorescence colocalization revealed that RELM-β is expressed in the endothelium and vascular smooth muscle of remodeled vessels, as well as in plexiform lesions, macrophages, T cells, and myofibroblast-like cells. We also show that addition of recombinant RELM-β induces proliferation and activation of ERK1/2 in primary cultured human pulmonary endothelial and smooth muscle cells. These results suggest that RELM-β may be involved in the development of scleroderma-associated pulmonary hypertension. PMID:19251945

  10. Association between circulating adiponectin levels and polycystic ovarian syndrome

    PubMed Central

    2014-01-01

    Background Low adiponectin levels in polycystic ovarian syndrome (PCOS) have been largely attributed to obesity which is common among these patients. In addition, evidence also suggests that low adiponectin in PCOS may be related to insulin resistance (IR) in these women. However, studies on the role of adiponectin in younger and lean patients are limited. Therefore, the aim of the present study was to examine the association of adiponectin levels in young and lean women with PCOS. Methods A case–control study was conducted at the Dow University of Health Sciences, Karachi, Pakistan. Cases were 75 patients of PCOS with Body Mass Index (BMI) &23 aged 16–35 years and 75 healthy age and BMI matched controls were selected from family and friends of the cases. Demographic details, family history and past medical history were obtained through interview by a physician. Anthropometric measurements included weight and height of the participants. Fasting glucose, total cholesterol, high-density lipoprotein (HDL), insulin, adiponectin, and androgen levels were determined. IR was calculated using homeostasis model assessment for insulin resistance (HOMA-IR). Logistic regression models were used to assess the association between adiponectin and PCOS after adjusting for co-variates. Results On multivariable analysis, PCOS cases were 3.2 times more likely to have low adiponectin level (OR = 3.2, 95% CI 1.49-6.90, p-value 0.003) compared to the controls after adjustment for age, BMI, family history, marital status, total cholesterol, HDL level and IR. Females with a family history of PCOS were significantly more likely to have lower adiponectin (OR = 3.32, 95% CI 1.27-8.67, p-value 0.014) compared to those who did not have a family history of PCOS. The associations of IR and family history with low adiponectin level also remained statistically significant after adjustments for covariates. Conclusion Serum adiponectin levels are independently associated with PCOS and

  11. Adiponectin-SOGA Dissociation in Type 1 Diabetes

    PubMed Central

    Snell-Bergeon, Janet K.; Maahs, David M.; Bergman, Bryan C.; Lamarche, Marie; Iberkleid, Laura; AbdelBaky, Omar; Tisch, Roland; Scherer, Philipp E.; Marliss, Errol B.

    2015-01-01

    Context: Circulating adiponectin is elevated in human type 1 diabetes (T1D) and nonobese diabetic (NOD) mice without the expected indications of adiponectin action, consistent with tissue resistance. Objective: Adiponectin stimulates hepatocyte production of the suppressor of glucose from autophagy (SOGA), a protein that inhibits glucose production. We postulated that due to tissue resistance, the elevation of adiponectin in T1D should fail to increase the levels of a surrogate marker for liver SOGA, the circulating C-terminal SOGA fragment. Main Outcome Measures: Liver and plasma SOGA were measured in NOD mice (n = 12) by Western blot. Serum adiponectin and SOGA were measured in T1D and control (Ctrl) participants undergoing a three-stage insulin clamp for the Coronary Artery Calcification in T1D study (n = 20). Glucose turnover was measured using 6,6[2H2]glucose (n = 12). Results: In diabetic NOD mice, the 13%–29% decrease of liver SOGA (P = .003) and the 30%–37% reduction of circulating SOGA (P < .001) were correlated (r = 0.826; P = .001). In T1D serum, adiponectin was 50%–60% higher than Ctrl, SOGA was 30%–50% lower and insulin was 3-fold higher (P < .05). At the low insulin infusion rate (4 mU/m2·min), the resulting glucose appearance correlated negatively with adiponectin in T1D (r = −0.985, P = .002) and SOGA in Ctrl and T1D (r = −0.837, P = .001). Glucose disappearance correlated with adiponectin in Ctrl (r = −0.757, P = .049) and SOGA in Ctrl and T1D (r = −0.709, P = .010). At 40 mU/m2·min, the lowered glucose appearance was similar in Ctrl and T1D. Glucose disappearance increased only in Ctrl (P = .005), requiring greater glucose infusion to maintain euglycemia (8.58 ± 1.29 vs 3.09 ± 0.87 mg/kg·min; P = .009). Conclusions: The correlation between liver and plasma SOGA in NOD mice supports the use of the latter as surrogate marker for liver concentration. Reduced SOGA in diabetic NOD mice suggests resistance to adiponectin. The

  12. Leptin and its receptor in hematologic malignancies

    PubMed Central

    Han, Tian-Jie; Wang, Xin

    2015-01-01

    Leptin is an adipocyte-derived cytokine coded by the obese gene, not only regulates metabolism, but also participates in hematopoiesis. Aberrant leptin levels in patients with hematologic malignancies were observed and associates with clinical characters, such as body mass index (BMI), gender, blast cell percentage. Leptin concentrations alter while diseases progress or remission. Leptin receptor is expressed in hematopoietic CD34+ stem cells, erythrocytes, lymphocytes, blast cells and samples in leukemia and lymphoma patients. The adipokine stimulates cell proliferation, cytokine secretion and protects malignant cells from apoptosis through Janus kinase-signal transducer and activator of transcription (JAK-STAT), mitogen-activated protein kinase and extracellular signal activated kinase 1/2 (MAPK/ERK1/2), or 3 kinase (PI3K) signaling pathways. These findings indicate leptin signaling possibility take part in occurrence, progression and prognosis of hematologic malignancies. This article reviews leptin/leptin receptor expression and the correlations with clinical characters, treatment and prognosis in myeloid and lymphoid neoplasms. PMID:26884894

  13. 20 years of leptin: role of leptin in human reproductive disorders.

    PubMed

    Chou, Sharon H; Mantzoros, Christos

    2014-10-01

    Leptin, as a key hormone in energy homeostasis, regulates neuroendocrine function, including reproduction. It has a permissive role in the initiation of puberty and maintenance of the hypothalamic-pituitary-gonadal axis. This is notable in patients with either congenital or acquired leptin deficiency from a state of chronic energy insufficiency. Hypothalamic amenorrhea is the best-studied, with clinical trials confirming a causative role of leptin in hypogonadotropic hypogonadism. Implications of leptin deficiency have also emerged in the pathophysiology of hypogonadism in type 1 diabetes. At the other end of the spectrum, hyperleptinemia may play a role in hypogonadism associated with obesity, polycystic ovarian syndrome, and type 2 diabetes. In these conditions of energy excess, mechanisms of reproductive dysfunction include central leptin resistance as well as direct effects at the gonadal level. Thus, reproductive dysfunction due to energy imbalance at both ends can be linked to leptin. PMID:25056118

  14. Plasma Adiponectin Levels in Elderly Patients with Prediabetes

    PubMed Central

    Kong, Si Eun; Kang, Yea Eun; Joung, Kyong Hye; Lee, Ju Hee; Kim, Hyun Jin

    2015-01-01

    Background The significance of adiponectin levels in elderly individuals with prediabetes has yet to be determined. Thus, the present study was performed to evaluate the relationships between adiponectin levels and anthropometric variables, body composition parameters, insulin sensitivity, and lipid profiles in elderly prediabetic patients. Methods The present study included 120 subjects with prediabetes who were >65 years of age and were selected from among 1,993 subjects enrolled in the Korea Rural Genomic Cohort Study. All subjects underwent a 75 g oral glucose tolerance test and tests for measurement of insulin sensitivity. All diagnoses of prediabetes satisfied the criteria of the American Diabetes Association. Results Plasma adiponectin levels were lower in elderly prediabetic subjects than elderly subjects with normal glucose tolerance (P<0.01) as well as in elderly prediabetic patients with metabolic syndrome (MetS) than in those without MetS (P<0.02). When the subjects were categorized into two groups according to plasma adiponectin levels, the waist-to-hip ratio and 2-hour insulin levels were significantly lower in individuals with high plasma adiponectin levels than in those with low plasma adiponectin levels. Additionally, the plasma adiponectin levels of elderly prediabetic subject were inversely correlated with body mass index (BMI), waist circumference (WC), waist-to-hip ratio, visceral fat, visceral fat ratio, and 2-hour insulin levels. Conclusion The present findings demonstrated that the major factors correlated with adiponectin levels in elderly prediabetic subjects were BMI, WC, waist-to-hip ratio, visceral fat, visceral fat ratio, and 2-hour insulin levels. PMID:26248857

  15. Adiponectin enhances the responsiveness of the olfactory system.

    PubMed

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

    2013-01-01

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

  16. Adiponectin Enhances the Responsiveness of the Olfactory System

    PubMed Central

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

    2013-01-01

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

  17. Allelic variation in porcine resistin (RETN) gene is associated with fatness traits in a Wild Boar x Meishan reference family

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cloning and comparative sequencing of the porcine resistin (RETN) gene and 5’ flanking region, located at 64 cM on SSC2, revealed 9 SNPs and 2 indels. A European Wild Boar x Meishan family encompassing 335 F2 animals measured for 46 traits including growth, fat deposition and muscle accretion was sc...

  18. Umbilical cord leptin predicts neonatal bone mass.

    PubMed

    Javaid, M K; Godfrey, K M; Taylor, P; Robinson, S M; Crozier, S R; Dennison, E M; Robinson, J S; Breier, B R; Arden, N K; Cooper, C

    2005-05-01

    Evidence is accumulating that the risk of osteoporosis in later life may be determined in part by environmental influences on bone development during intrauterine and early postnatal life. A potential role for fetal leptin in mediating these effects is suggested by animal studies showing that leptin influences prenatal osteoblast growth and development, and that fetal leptin concentrations are altered by changes in maternal nutrition. In a group of term human infants we reported previously that maternal birthweight, smoking, fat mass, and exercise during late pregnancy independently predict neonatal bone mass. To investigate the potential role of leptin in mediating these effects, we now relate leptin concentrations in umbilical venous serum to neonatal bone mass and body composition in 117 infants. There were strong positive associations between umbilical venous leptin concentration and each of whole body bone mineral contents (BMC) (r = 0.42, P < or = 0.001) and estimated volumetric bone density (r = 0.21, P = 0.02); whole body lean mass (r = 0.21, P < or = 0.024); and whole body fat mass (r = 0.60, P < 0.001). The associations with neonatal BMC and fat mass, but not with lean mass, were independent of associations that we have reported previously between cord serum insulin-like growth factor 1 (IGF-1) concentrations and neonatal body composition. Among the maternal determinants of neonatal bone mass, cord leptin explained the relationship with maternal fat stores, but not those with the mother's own birthweight, smoking, or physical activity. We conclude that umbilical venous leptin predicts both the size of the neonatal skeleton and its estimated volumetric mineral density. In addition, among previously documented maternal determinants of neonatal bone mass in healthy pregnancies, maternal fat stores may mediate their effect on fetal bone accrual through variation in fetal leptin concentrations. PMID:15864467

  19. Leptin as well as Free Leptin Receptor Is Associated with Polycystic Ovary Syndrome in Young Women

    PubMed Central

    Rizk, Nasser M.; Sharif, Elham

    2015-01-01

    Background and Aim. Leptin has two forms in the circulation: free and bound forms. The soluble leptin receptor (sOB-R) circulates in the blood and can bind to leptin. The aim of this study is to assess the concentrations of the leptin and the sOB-R in PCOS and its relation to adiposity, insulin resistance, and androgens. Methods. A cross-sectional study included 78 female students aged 17–25 years. Fasting serum leptin and sOB-R concentrations were measured. The anthropometric variables and the hormonal profile such as insulin, female and male sex hormones, and prolactin were assessed. Results. In PCOS, leptin level (ng/ml) and free leptin index (FLI) increased significantly while sOB-R (ng/ml) significantly decreased compared to control subjects. In age-matched subjects, obese PCOS had increased leptin level in ng/ml (median level with interquartile levels) of 45.67 (41.98–48.04) and decreased sOB-R in ng/ml 11.47 (7.59–16.44) compared to lean PCOS 16.97 (10.60–45.55) for leptin and 16.62 (11.61–17.96) for sOB-R with p values 0.013 and 0.042, respectively. However, body mass index (BMI) is significantly correlated with leptin and s-OBR, while no significant correlations with parameters of insulin resistance were detected. Conclusion. PCOS is associated with hyperleptinemia and increased free leptin index. Decreased sOB-R could be a compensatory mechanism for the defective action of leptin. PMID:26180527

  20. Phocid seal leptin: tertiary structure and hydrophobic receptor binding site preservation during distinct leptin gene evolution.

    PubMed

    Hammond, John A; Hauton, Chris; Bennett, Kimberley A; Hall, Ailsa J

    2012-01-01

    The cytokine hormone leptin is a key signalling molecule in many pathways that control physiological functions. Although leptin demonstrates structural conservation in mammals, there is evidence of positive selection in primates, lagomorphs and chiropterans. We previously reported that the leptin genes of the grey and harbour seals (phocids) have significantly diverged from other mammals. Therefore we further investigated the diversification of leptin in phocids, other marine mammals and terrestrial taxa by sequencing the leptin genes of representative species. Phylogenetic reconstruction revealed that leptin diversification was pronounced within the phocid seals with a high dN/dS ratio of 2.8, indicating positive selection. We found significant evidence of positive selection along the branch leading to the phocids, within the phocid clade, but not over the dataset as a whole. Structural predictions indicate that the individual residues under selection are away from the leptin receptor (LEPR) binding site. Predictions of the surface electrostatic potential indicate that phocid seal leptin is notably different to other mammalian leptins, including the otariids. Cloning the grey seal leptin binding domain of LEPR confirmed that this was structurally conserved. These data, viewed in toto, support a hypothesis that phocid leptin divergence is unlikely to have arisen by random mutation. Based upon these phylogenetic and structural assessments, and considering the comparative physiology and varying life histories among species, we postulate that the unique phocid diving behaviour has produced this selection pressure. The Phocidae includes some of the deepest diving species, yet have the least modified lung structure to cope with pressure and volume changes experienced at depth. Therefore, greater surfactant production is required to facilitate rapid lung re-inflation upon surfacing, while maintaining patent airways. We suggest that this additional surfactant requirement

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

    SciTech Connect

    Zappala, Giovanna; Rechler, Matthew M.

    2009-05-15

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

  2. Adiponectin as a Biomarker of Osteoporosis in Postmenopausal Women: Controversies

    PubMed Central

    Dobek, Aleksandra; Garczynski, Wojciech; Chlubek, Dariusz

    2014-01-01

    The literature reports indicating a link between plasma levels of adiponectin and body fat, bone mineral density, sex hormones, and peri- and postmenopausal changes, draw attention to the possible use of adiponectin as an indicator of osteoporotic changes, suggesting that adiponectin may also modulate bone metabolism. In this study, we attempted to analyze the available in vitro and in vivo results which could verify this hypothesis. Although several studies have shown that adiponectin has an adverse effect on bone mass, mainly by intensifying resorption, this peptide has also been demonstrated to increase the proliferation and differentiation of osteoblasts, inhibit the activity of osteoclasts, and reduce bone resorption. There are still many ambiguities; for example, it can be assumed that concentrations of adiponectin in plasma do not satisfactorily reflect its production by adipose tissue, as well as conflicting in vitro and in vivo results. It seems that the potential benefit in the treatment of patients with osteoporosis associated with the pharmacological regulation of adiponectin is controversial. PMID:24591772

  3. Leptin replacement alters brain response to food cues in genetically leptin-deficient adults

    PubMed Central

    Baicy, Kate; London, Edythe D.; Monterosso, John; Wong, Ma-Li; Delibasi, Tuncay; Sharma, Anil; Licinio, Julio

    2007-01-01

    A missense mutation in the ob gene causes leptin deficiency and morbid obesity. Leptin replacement to three adults with this mutation normalized body weight and eating behavior. Because the neural circuits mediating these changes were unknown, we paired functional magnetic resonance imaging (fMRI) with presentation of food cues to these subjects. During viewing of food-related stimuli, leptin replacement reduced brain activation in regions linked to hunger (insula, parietal and temporal cortex) while enhancing activation in regions linked to inhibition and satiety (prefrontal cortex). Leptin appears to modulate feeding behavior through these circuits, suggesting therapeutic targets for human obesity. PMID:17986612

  4. The Relationship Between Gene Polymorphism of Leptin and Leptin Receptor and Growth Hormone Deficiency.

    PubMed

    He, Jinshui; Fang, Yanling; Lin, Xinfu; Zhou, Huowang; Zhu, Shaobo; Zhang, Yugui; Yang, Huicong; Ye, Xiaoling

    2016-01-01

    BACKGROUND Growth hormone deficiency (GHD) is a major cause of congenital short stature. GHD patients have significantly decreased serum leptin levels, which are regulated by gene polymorphism of leptin and leptin receptor. This study thus investigated the relationship between gene polymorphism and susceptibility to GHD. MATERIAL AND METHODS A case-control study was performed using 180 GHD children in addition to 160 healthy controls. After the extraction of whole genomic DNA, the genotypes of leptin and leptin receptor gene loci were analyzed by sequencing for single-nucleotide polymorphism. RESULTS The frequency distribution of all alleles identified in leptin gene (loci rs7799039) and leptin receptor gene (loci rs1137100 and rs1137101) fit Hardy-Weinberg equilibrium. There was a significant difference in allele frequency at loci rs7799039 or rs1137101, as individuals with heterozygous GA allele had lower (rs7799039) or higher (rs1137101) GHD risk. No significant difference in allele frequency was discovered at loci rs1137100 (p>0.05), which was unrelated to GHD susceptibility. CONCLUSIONS Gene polymorphism of leptin (loci rs7799039) and leptin receptor (loci rs1137101) are correlated with GHD susceptibility. PMID:26915772

  5. The Relationship Between Gene Polymorphism of Leptin and Leptin Receptor and Growth Hormone Deficiency

    PubMed Central

    He, Jinshui; Fang, Yanling; Lin, Xinfu; Zhou, Huowang; Zhu, Shaobo; Zhang, Yugui; Yang, Huicong; Ye, Xiaoling

    2016-01-01

    Backgrounds Growth hormone deficiency (GHD) is a major cause of congenital short stature. GHD patients have significantly decreased serum leptin levels, which are regulated by gene polymorphism of leptin and leptin receptor. This study thus investigated the relationship between gene polymorphism and susceptibility to GHD. Material/Methods A case-control study was performed using 180 GHD children in addition to 160 healthy controls. After the extraction of whole genomic DNA, the genotypes of leptin and leptin receptor gene loci were analyzed by sequencing for single-nucleotide polymorphism. Results The frequency distribution of all alleles identified in leptin gene (loci rs7799039) and leptin receptor gene (loci rs1137100 and rs1137101) fit Hardy-Weinberg equilibrium. There was a significant difference in allele frequency at loci rs7799039 or rs1137101, as individuals with heterozygous GA allele had lower (rs7799039) or higher (rs1137101) GHD risk. No significant difference in allele frequency was discovered at loci rs1137100 (p>0.05), which was unrelated to GHD susceptibility. Conclusions Gene polymorphism of leptin (loci rs7799039) and leptin receptor (loci rs1137101) are correlated with GHD susceptibility. PMID:26915772

  6. Genetic variants in leptin: Determinants of obesity and leptin levels in South Indian population

    PubMed Central

    Dasgupta, Shruti; Salman, Mohammed; Siddalingaiah, Lokesh B; Lakshmi, GL; Xaviour, D; Sreenath, Jwalapuram

    2014-01-01

    The revelation of leptin action mechanisms has led to various attempts to establish the association of polymorphisms in the leptin gene with obesity-related phenotypes. But, outcomes have been contradicting, which made the information on the role of the leptin gene in regulating the mechanism of pathophysiology of obesity inexplicable. Moreover, none of the studies are known to have similar implications on the Indian population. To address such contradictions, our study aims to evaluate the association of leptin gene polymorphism with obesity and leptin levels in a South Indian Population. A total of 304 cases (BMI≥27.5) and 309 controls (BMI≤23) from local inhabitants of Mysore, Karnataka were recruited for the study. The leptin gene variants rs7799039, rs2167270 and rs4731426 independently, as well as in 4 haplotype combinations, were found to be significantly associated with the risk of obesity. An increasing trend in BMI and leptin levels was observed with every addition of A and C minor alleles of exonic variant (rs2167270) and intronic variant (rs4731426) respectively. However, only AA genotype of SNP rs7799039 was positively associated with BMI. None of the SNPs were associated with fat percentage and waist to hip ratio. On a whole, this data suggests that the common polymorphisms in the leptin gene are strong predictors of obesity and leptin levels in South Indians. PMID:26167411

  7. Variants in the Adiponectin Gene and Serum Adiponectin: The Coronary Artery Development in Young Adults (CARDIA) Study

    PubMed Central

    Wassel, Christina L.; Pankow, James S.; Jacobs, David R.; Steffes, Michael W.; Li, Na; Schreiner, Pamela J.

    2016-01-01

    Circulating adiponectin is involved in the atherosclerotic process and has been associated with cardiovascular disease as well as obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. The adiponectin gene (ADIPOQ) encodes the circulating protein adiponectin and affects its expression. Only a small proportion of all known ADIPOQ polymorphisms have been investigated in relation to circulating adiponectin concentrations. Using data from 3,355 African-American and white men and women aged 33–45 at the year 15 examination from the Coronary Artery Development in Young Adults (CARDIA) Study the association between 10 single-nucleotide polymorphisms (SNPs) within ADIPOQ and serum adiponectin was examined using linear regression. SNPs were chosen based on a tagSNP approach. Models were stratified by self-reported race to control for population stratification, and Bonferroni corrected for multiple comparisons. ADIPOQ SNPs rs17300539 (P < 0.0001), rs182052 (P = 0.0013), rs822393 (P = 0.0005), rs9882205 (P = 0.0001), and rs3774261 (P = 0.0001) were strongly associated with serum adiponectin concentrations in whites. In general, there was a dose–response relationship of adjusted mean adiponectin concentrations across genotypes. Only one SNP, rs17300539 was marginally associated with serum adiponectin concentrations (P = 0.0087) in African Americans. Significant interactions were found between waist and rs182052 (P = 0.0029) and between rs9882505 and smoking (P = 0.001) in whites. Many ADIPOQ SNPs have not yet been examined, and additional studies are needed to determine whether these may be functional variants. PMID:20395949

  8. Resistin gene polymorphisms are associated with acne and serum lipid levels, providing a potential nexus between lipid metabolism and inflammation.

    PubMed

    Younis, Sidra; Blumenberg, Miroslav; Javed, Qamar

    2016-05-01

    Acne vu lgaris is a multifactorial inflammatory skin disease causing social stigma and psychological effect on patients. We hypothesized that the genes that can affect both lipid metabolism and inflammation may be central for acne formation and present targets for treatment. Pro-inflammatory adipokine resistin, one such likely target, activates NFkB and JNK pathways inducing TLR-2, IL-1, IL-6, and TNFα genes. The polymorphisms in promoter and intron region of the resistin gene affect its expression levels. Therefore, we explored the association of resistin polymorphisms (RETN +299G > A and -420C > G) with pathogenesis of acne vulgaris. We used PCR-RFLP method to genotype at the two single nucleotide polymorphisms at RETN promoter in 530 acne patients vs. 550 age- and sex-matched control subjects. We also measured serum lipid levels in acne patients and associated these with RETN genotypes. We found that the RETN gene polymorphisms are strongly associated with acne vulgaris and the severity of acne symptoms. In females the variant allele frequencies of both SNPs are statistically higher in patients than in controls; in males frequency distribution does not reach significance. The haplotype containing both variant alleles is significantly more common in patients than in controls. We find no association of RETN SNPs with the acne types. Importantly, we found that the levels of HDL-C were significantly decreased in variant genotype of RETN. Our results show that the RETN polymorphisms expected to boost resistin expression increase the risk of developing acne. We suggest that resistin may provide an attractive target for treatment. PMID:26858108

  9. The role of leptin in regulating bone metabolism

    PubMed Central

    Upadhyay, Jagriti; Farr, Olivia M.; Mantzoros, Christos S.

    2015-01-01

    Leptin was initially best known for its role in energy homeostasis and regulation of energy expenditure. In the past few years we have realized that leptin also plays a major role in neuroendocrine regulation and bone metabolism. Here, we review the literature on indirect and direct pathways through which leptin acts to influence bone metabolism and discuss bone abnormalities related to leptin deficiency in both animal and human studies. The clinical utility of leptin in leptin deficient individuals and its potential to improve metabolic bone disease are also discussed. We are beginning to understand the critical role leptin plays in bone metabolism; future randomized studies are needed to fully assess the potential and risk – benefit of leptin's use in metabolic bone disease particularly in leptin deficient individuals. PMID:25497343

  10. Vascular smooth muscle cell-derived adiponectin: a paracrine regulator of contractile phenotype.

    PubMed

    Ding, Min; Carrão, Ana Catarina; Wagner, Robert J; Xie, Yi; Jin, Yu; Rzucidlo, Eva M; Yu, Jun; Li, Wei; Tellides, George; Hwa, John; Aprahamian, Tamar R; Martin, Kathleen A

    2012-02-01

    Adiponectin is a cardioprotective adipokine derived predominantly from visceral fat. We recently demonstrated that exogenous adiponectin induces vascular smooth muscle cell (VSMC) differentiation via repression of mTORC1 and FoxO4. Here we report for the first time that VSMC express and secrete adiponectin, which acts in an autocrine and paracrine manner to regulate VSMC contractile phenotype. Adiponectin was found to be expressed in human coronary artery and mouse aortic VSMC. Importantly, siRNA knock-down of endogenous adiponectin in VSMC significantly reduced the expression of VSMC contractile proteins. Contractile protein deficiency was also observed in primary VSMC isolated from Adiponectin(-/-) mice. This deficiency could be rescued by culturing Adiponectin(-/-) VSMC in conditioned media from wild type (WT) VSMC. Moreover, the paracrine effect of VSMC-derived adiponectin was confirmed as adiponectin neutralizing antibody blocked the rescue. Overexpressed adiponectin also exerted paracrine effects on neighboring untransfected VSMC, which was also blocked by adiponectin neutralizing antibody. Interestingly, adiponectin expression was inducible by the PPARγ agonist rosiglitazone. Our data support an important role for VSMC-derived adiponectin in maintaining VSMC contractile phenotype, contributing to critical cardioprotective functions in the vascular wall. This article is part of a Special Issue entitled "Local Signaling in Myocytes". PMID:21952104

  11. Mechanisms mediating renal sympathetic nerve activation in obesity-related hypertension.

    PubMed

    Chen, W; Leo, S; Weng, C; Yang, X; Wu, Y; Tang, X

    2015-04-01

    Excessive renal sympathetic nerve activation may be one of the mechanisms underlying obesity-related hypertension. Impaired baroreflex sensitivity, adipokine disorders-such as leptin, adiponectin, and resistin-activation of the renin-angiotensin system, hyperinsulinemia, insulin resistance, and renal sodium retention present in obesity increase renal sympathetic nerve activity, thus contributing to the development of hypertension. Renal sympathetic denervation reduces both renal sympathetic activity and blood pressure in patients with obesity-related hypertension. PMID:24609799

  12. Genetics Home Reference: leptin receptor deficiency

    MedlinePlus

    ... leptin receptor gene causes obesity and pituitary dysfunction. Nature. 1998 Mar 26;392(6674):398-401. Citation ... and human weight regulation: lessons from experiments of nature. Ann Acad Med Singapore. 2009 Jan;38(1): ...

  13. Assessment of ghrelin and leptin receptor levels in postmenopausal women who received oral or transdermal menopausal hormonal therapy*

    PubMed Central

    Ruszkowska, Barbara; Sokup, Alina; Kulwas, Arleta; Socha, Maciej W.; Góralczyk, Krzysztof; Góralczyk, Barbara; Rość, Danuta

    2012-01-01

    Objective: In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghrelin, total ghrelin, leptin receptor, lipoprotein(a) (Lp(a)), and plasminogen activator inhibitor type 1 (PAI-1) in postmenopausal women who received oral or transdermal menopausal hormonal therapy (MHT). Methods: The study involved 76 healthy women: 46 women aged from 44 to 58 years who received oral (26) or transdermal (20) MHT; the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT. The plasma concentrations of total ghrelin, the active form of ghrelin, Lp(a), and PAI-1:Ag were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of the leptin receptor was measured by enzyme immunometric assay (EIA). Results: We observed a significantly higher concentration of total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT. We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group. A higher concentration of PAI-1:Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group. The differences were statistically significant. Additionally, we found a significant negative correlation between the concentrations of total ghrelin and PAI-1:Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT. Conclusions: The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT. This indicates a beneficial effect of the transdermal route of MHT. However, transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAI-1:Ag, which in turn, can lead to

  14. Similar Adiponectin Levels in Obese Normotensive and Obese Hypertensive Men and No Vasorelaxant Effect of Adiponectin on Human Arteries.

    PubMed

    Dreier, Rasmus; Asferg, Camilla; Berg, Jais O; Andersen, Ulrik B; Flyvbjerg, Allan; Frystyk, Jan; Linneberg, Allan; Jeppesen, Jørgen L; Edvinsson, Lars; Skovsted, Gry F

    2016-02-01

    Obesity is a strong risk factor for hypertension, but the mechanism linking obesity to hypertension is not fully elucidated. In obesity, circulating concentrations of adiponectin are decreased and hypoadiponectinaemia has in some but not all studies been associated with increased risk of hypertension. Due to this inconsistency, we decided to study adiponectin from two aspects in a cross-sectional in vivo study and in an experimental in vitro study. In the cross-sectional study, 103 men with body mass index (BMI) ≥ 30.0 kg/m(2) were studied; 63 had 24-hr ambulatory blood pressure (ABP) ≥ 130/80 mmHg (ObeseHT) and 40 had 24-hr ABP < 130/80 mmHg (ObeseNT). As controls, we studied 27 men with BMI between 20.0 and 24.9 kg/m(2) and 24-hr ABP < 130/80 mmHg (LeanNT). Serum concentrations of adiponectin and body composition using dual-energy X-ray absorptiometry scanning were determined. In vitro, the direct vasomotor response of adiponectin was tested on subcutaneous resistance arteries from human abdominal adipose tissue. The two obese groups had lower adiponectin concentrations compared with LeanNT (p < 0.01) [median (interquartile range)]: ObeseHT 6.5 (5.1-8.3) mg/L; ObeseNT 6.6 (5.2-7.8) mg/L; and LeanNT 9.4 (6.7-12.4) mg/L, with no significant difference in adiponectin concentrations (or body composition) between ObeseHT and ObeseNT (p = 0.67). In vitro, adiponectin did not have any direct vasodilatory effect and adiponectin did not affect angiotensin II-stimulated vasoconstriction. In conclusion, obese hypertensive men have similar serum concentrations of adiponectin as obese normotensive men. In combination with the in vitro data, these findings question a pathogenic role of adiponectin in human hypertension. PMID:26272341

  15. Leptin and endocrine parameters in marathon runners.

    PubMed

    Bobbert, T; Mai, K; Brechtel, L; Schulte, H M; Weger, B; Pfeiffer, A F H; Spranger, J; Diederich, S

    2012-03-01

    Endurance training may lead to different hormonal alterations e. g., exercised induced hypothalamic ovarian/testicular dysfunction. The aim of this study was to reveal new connections between physical exercise, leptin and hormonal responses. 36 male participants of the Berlin-Marathon had their blood samples taken 2 days before the marathon. Hormones of the hypothalamic-pituitary axis and leptin were correlated with the training status and the achieved marathon time. Leptin correlated with the achieved marathon time after being adjusted for age and BMI (r=0.607, p<0.001) and was lowest in the best trained runners. Additionally, when the group was divided into quartiles of their achieved marathon time, significantly increased cortisol, fT4, cortisol/DHEAS ratio and decreased IGF-1 levels were observed in the slowest group. In the better trained group, a decrease of testosterone/DHT ratio and an increase of testosterone/cortisol ratio were observed. Our study supports the thesis of a linear relationship between physical fitness and leptin variations in the physiological range. We found an increased anabolic hormonal response in well trained marathon runners and hormonal reactions of increased stress in less trained runners. As the stress-induced neuroendocrine adaptations in our study group are associated with more higher leptin values, the pathophysiological role of decreased leptin values seems to be limited to overtrained athletes. PMID:22261828

  16. Resistin gene variation is associated with systemic inflammation but not plasma adipokine levels, metabolic syndrome or coronary atherosclerosis in nondiabetic Caucasians

    PubMed Central

    Qasim, Atif N.; Metkus, Thomas S.; Tadesse, Mahlet; Lehrke, Michael; Restine, Stephanie; Wolfe, Megan L.; Hannenhalli, Sridhar; Cappola, Thomas; Rader, Daniel J.; Reilly, Muredach P.

    2011-01-01

    Summary Objective Resistin causes insulin resistance and diabetes in mice whereas in humans it is linked to inflammation and atherosclerosis. Few human genetic studies of resistin in inflammation and atherosclerosis have been performed. We hypothesized that the −420C>G putative gain-of-function resistin variant would be associated with inflammatory markers and atherosclerosis but not with metabolic syndrome or adipokines in humans. Design and methods We examined the association of three resistin polymorphisms, −852A>G, −420C>G and +157C>T, and related haplotypes with plasma resistin, cytokines, C-reactive protein (CRP), adipokines, plasma lipoproteins, metabolic syndrome and coronary artery calcification (CAC) in nondiabetic Caucasians (n = 851). Results Resistin levels were higher, dose-dependently, with the −420G allele (CC 5·9 ± 2·7 ng/ml, GC 6·5 ± 4·0 ng/ml and GG 7·2 ± 4·8 ng/ml, trend P = 0·04) after age and gender adjustment [fold higher for GC + GG vs. CC; 1·07 (1·00–1·15), P < 0·05)]. The −852A>G single nucleotide polymorphism (SNP) was associated with higher soluble tumour necrosis factor-receptor 2 (sol-TNFR2) levels in fully adjusted models [1·06 (95% CI 1·01–1·11), P = 0·01)]. The estimated resistin haplotype (GGT) was associated with sol-TNFR2 (P = 0·04) and the AGT haplotype was related to CRP (P = 0·04) in the fully adjusted models. Resistin SNPs and haplotypes were not associated with body mass index (BMI), fasting glucose, insulin resistance, metabolic syndrome, adipokines or CAC scores. Conclusions Despite modest associations with plasma resistin and inflammatory biomarkers, resistin 5′ variants were not associated with metabolic parameters or coronary calcification. This suggests that resistin is an inflammatory cytokine in humans but has little influence on adiposity, metabolic syndrome or atherosclerosis. PMID:18710472

  17. 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.

  18. Adiponectin Action: A Combination of Endocrine and Autocrine/Paracrine Effects

    PubMed Central

    Dadson, Keith; Liu, Ying; Sweeney, Gary

    2011-01-01

    The widespread physiological actions of adiponectin have now been well characterized as clinical studies and works in animal models have established strong correlations between circulating adiponectin level and various disease-related outcomes. Thus, conventional thinking attributes many of adiponectin’s beneficial effects to endocrine actions of adipose-derived adiponectin. However, it is now clear that several tissues can themselves produce adiponectin and there is growing evidence that locally produced adiponectin can mediate functionally important autocrine or paracrine effects. In this review article we discuss regulation of adiponectin production, its mechanism of action via receptor isoforms and signaling pathways, and its principal physiological effects (i.e., metabolic and cardiovascular). The role of endocrine actions of adiponectin and changes in local production of adiponectin or its receptors in whole body physiology is discussed. PMID:22649379

  19. Lung tumor-associated dendritic cell-derived resistin promoted cancer progression by increasing Wolf-Hirschhorn syndrome candidate 1/Twist pathway.

    PubMed

    Kuo, Chih-Hsin; Chen, Kuei-Fang; Chou, Shah-Hwa; Huang, Ya-Fang; Wu, Cheng-Ying; Cheng, Da-En; Chen, Yu-Wen; Yang, Chih-Jen; Hung, Jen-Yu; Huang, Ming-Shyan

    2013-11-01

    The interaction between tumors and their microenvironments leads to a vicious cycle, which strengthens both immune suppression and cancer progression. The present study demonstrates for the first time that tumor-associated dendritic cells (TADCs) are a source of resistin, which is responsible for increasing lung cancer epithelial-to-mesenchymal transition. In addition, large amounts of resistin in the condition medium (CM) of TADCs increase cell migration and invasion, as well as the osteolytic bone metastatic properties of lung cancer cells. Neutralization of resistin from TADC-CM prevents the advanced malignancy-inducing features of TADC-CM. Significantly elevated levels of resistin have been observed in mice transplanted with lung cancer cells, tumor-infiltrating CD11c(+) DCs in human lung cancer samples and lung cancer patients' sera. Induction of lung cancer progression by TADC-derived resistin is associated with increased expression of Wolf-Hirschhorn syndrome candidate 1 (WHSC1), a histone methyltransferase. Resistin-induced WHSC1 increases the dimethylation of histone 3 at lysine 36 and decreases the trimethylation of histone 3 at lysine 27 on the promoter of Twist, resulting in an enhancement of the expression of Twist. Knockdown of WHSC1 by small interfering RNA transfection significantly decreases resistin-mediated cancer progression by decreasing the upregulation of Twist, suggesting that WHSC1 plays a critical role in the regulation of Twist by epigenetic modification. Furthermore, mice that received antiresistin antibodies showed a decreased incidence of cancer development and metastasis. These findings suggest that TADC-derived resistin may be a novel candidate in promoting the development of lung cancer. PMID:23955539

  20. Evaluation of Adipokines, Inflammatory Markers, and Sex Hormones in Simple and Complex Breast Cysts' Fluid

    PubMed Central

    Madej, Paweł; Franik, Grzegorz; Kurpas, Piotr; Olszanecka-Glinianowicz, Magdalena

    2016-01-01

    Objective. The aim of the study was to analyze the association between levels of adipokines in the breast cyst fluid and in the circulation in relation to the type of cysts. Material and Measurements. A cross-sectional study involved 86 women with breast cysts (42 with simple cysts and 44 with complex cysts). Plasma and breast cyst fluid leptin, adiponectin, visfatin/NAMPT, resistin, TNF-α, and IL-6 levels, in addition to serum levels of estradiol, progesterone and prolactin, and anthropometric parameters and body composition (by bioimpedance method), were measured. Results. The levels of leptin, adiponectin, and resistin were significantly lower in breast cyst fluid than in plasma regardless of the cyst type. Contrarily, the levels of visfatin/NAMPT and TNF-α were significantly increased, and IL-6 levels were similar in the breast cyst fluid and plasma in both study groups. There was no correlation between corresponding levels of leptin, adiponectin, resistin, visfatin/NAMPT, TNF-α, and IL-6 in breast cyst fluid and plasma. Conclusions. Higher levels of visfatin/NAMPT and TNF-α in the fluid from simple and complex breast cysts than in plasma suggest that their local production is related to inflammation. PMID:27293305

  1. Milk leptin in sows and blood leptin and growth of their offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Twenty-one mixed parity (average 2.4 ± 0.49) crossbred sows and their offspring were used to determine if sow milk leptin at farrowing was related to neonatal serum leptin and pig growth to weaning. During farrowing, pigs were randomly allotted to suckled (n=99) or unsuckled (n = 89) groups with uns...

  2. Implications of leptin in neuroendocrine regulation of male reproduction.

    PubMed

    Landry, David; Cloutier, Frank; Martin, Luc J

    2013-03-01

    Obesity is a major health problem contributing to increased subfertility in males, as well as increased morbidity for diseases related to a decline in testosterone production with aging. Leptin is a hormone produced by adipose tissue whose production increases with the amount of body fat. Several studies have supported a relationship between increased leptin production and regulation of reproductive function. Indeed, leptin acts at all levels of the hypothalamus-pituitary-gonadal (HPG) axis in males. However, most of the obese individuals become insensitive to increased endogenous leptin production and develop a functional leptin resistance. This deregulation of leptin signaling might result in abnormal endocrine and reproductive functions. Altered leptin dynamics may contribute to male infertility in different ways, leading to hypogonadism. These include leptin resistance or leptin insufficiency at the hypothalamus and leptin modulation of testicular physiology. In this review, we address the mechanisms of action of leptin at different levels of the HPG axis. Moreover, the influences of leptin on steroidogenesis and spermatogenesis, as well as seasonal variations of leptin's action on male reproduction are discussed. PMID:23522066

  3. Resistin, visfatin and insulin sensitivity in selected phases of annual training cycle of triathletes.

    PubMed

    Sliwicka, Ewa; Pilaczyńska-Szcześniak, L; Nowak, A; Zieliński, J

    2012-03-01

    The purpose of the study was to examine the effects of sport training on carbohydrate metabolic indices and adipokines concentrations in young male triathletes (n=10). Athletes performed the incremental running test in two periods of the training cycle: in the transitory and preparatory phases. In both analyzed terms, physical exercise was reflected by a significant increase in lactate (p≤0.01), insulin (p≤0.01), visfatin concentrations (p≤0.01, p<0.05, respectively) and only during transitory phase in glucose (p≤0.01) and resistin concentrations (p<0.05). Significant inter-period differences were noted in the pre-exercise insulin (p≤0.01) and also in pre- and post-exercise visfatin concentrations (p<0.05). Additionally, the differences (Δ) between post- and pre-exercise values of glucose (p<0.05) and visfatin (p≤0.01) significantly decreased in the preparatory phase comparing to the transitory phase. The inverse correlations between pre-exercise concentrations of visfatin and peak oxygen uptake (p<0.05) in the transitory phase and between post- and pre-exercise differences (Δ) of visfatin and lactate concentrations (p<0.05) in the preparatory phase were noted. During preparatory phase, pre-exercise visfatin concentrations inversely correlated with pre-exercise resistin, insulin and glucose levels (p<0.05). In conclusion, systematic training in elite triathletes modulates basal adipokine concentrations only to a small extent, however, influences on these molecules response on the acute exercise. PMID:22425808

  4. Carboxylated and intact osteocalcin predict adiponectin concentration in hemodialyzed patients.

    PubMed

    Kuźniewski, Marek; Fedak, Danuta; Dumnicka, Paulina; Kapusta, Maria; Stępień, Ewa; Chowaniec, Eve; Krzanowska, Katarzyna; Krzanowski, Marcin; Chmiel, Grzegorz; Solnica, Bogdan; Sułowicz, Władysław

    2016-01-01

    Purpose Disrupted bone metabolism in patients with chronic kidney disease (CKD) is associated with elevated concentrations of biochemical bone markers. Recently, animal studies show the role of osteocalcin in energy metabolism, which is partially confirmed in humans. The aim of our study was to evaluate the relationships between serum concentrations of bone markers and indices of energy metabolism in CKD patients on maintenance hemodialysis; in particular, the relationship between various forms of osteocalcin and adiponectin. Patients and methods The cross-sectional study included 155 hemodialyzed stage 5 CKD patients. Serum concentrations of glucose, insulin, adiponectin, bone alkaline phosphatase (bALP), tartrate resistant acid phosphatase (TRAP), carboxylated (cOC), undercarboxylated (ucOC), and intact osteocalcin (OC) were determined. Results In total cohort, bALP, TRAP, cOC, and ucOC negatively correlated with BMI. All analyzed bone markers positively correlated with adiponectin in total cohort and in men. In multiple linear regression analysis including all patients, log(cOC) and log(intact OC) were the only bone markers that predicted log(adiponectin) (beta = 0.22; p = 0.016 and beta = 0.26; p = 0.010) independently of sex, dialysis vintage, CRP, insulin, iPTH concentrations, BMI, and age. Conclusions Our data confirm the positive association between cOC, intact OC, and adiponectin concentrations in CKD patients on maintenance hemodialysis. PMID:26822199

  5. Total and High Molecular Weight Adiponectin Levels and Prediction of Cardiovascular Risk in Diabetic Patients

    PubMed Central

    Horáková, Dagmar; Azeem, Kateřina; Benešová, Radka; Pastucha, Dalibor; Horák, Vladimír; Dumbrovská, Lenka; Martínek, Arnošt; Novotný, Dalibor; Hobzová, Milada; Galuszková, Dana; Janout, Vladimír; Doněvská, Sandra; Vrbková, Jana; Kollárová, Helena

    2015-01-01

    The study aimed at assessing the potential use of lower total and HMW adiponectin levels for predicting cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). Concentrations of total adiponectin or high molecular weight (HMW) adiponectin decrease in association with the development of metabolic dysfunction such as obesity, insulin resistance, or T2DM. Increased adiponectin levels are associated with a lower risk for coronary heart disease. A total of 551 individuals were assessed. The first group comprised metabolically healthy participants (143 females, and 126 males) and the second group were T2DM patients (164 females, and 118 males). Both total adiponectin and HMW adiponectin in diabetic patients were significantly lower when compared with the group of metabolically healthy individuals. There was a weak monotonic correlation between HMW adiponectin levels and triglycerides levels. Binary logistic regression analysis, gender adjusted, showed a higher cardiovascular risk in diabetic persons when both total adiponectin (OR = 1.700) and HMW adiponectin (OR = 2.785) levels were decreased. A decrease in total adiponectin levels as well as a decrease in its HMW adiponectin is associated with a higher cardiovascular risk in individuals with T2DM. This association suggests that adiponectin levels may be potentially used as an epidemiological marker for cardiovascular risk in diabetic patients. PMID:26074960

  6. Vagal hyperactivity due to ventromedial hypothalamic lesions increases adiponectin production and release.

    PubMed

    Suzuki, Yoko; Shimizu, Hiroyuki; Ishizuka, Noriko; Kubota, Naoto; Kubota, Tetsuya; Senoo, Akira; Kageyama, Haruaki; Osaka, Toshimasa; Hirako, Satoshi; Kim, Hyoun-Ju; Matsumoto, Akiyo; Shioda, Seiji; Mori, Masatomo; Kadowaki, Takashi; Inoue, Shuji

    2014-05-01

    In obese humans and animals, adiponectin production and release in adipose tissue are downregulated by feedback inhibition, resulting in decreased serum adiponectin. We investigated adiponectin production and release in ventromedial hypothalamic (VMH)-lesioned animals. VMH-lesioned mice showed significant increases in food intake and body weight gain, with hyperinsulinemia and hyperleptinemia at 1 and 4 weeks after VMH-lesioning. Serum adiponectin was elevated in VMH-lesioned mice at 1 and 4 weeks, despite adipocyte hypertrophy in subcutaneous and visceral adipose tissues and increased body fat. Adiponectin production and mRNA were also increased in both adipose tissues in VMH-lesioned mice at 1 week. These results were replicated in VMH-lesioned rats at 1 week. Daily atropine administration for 5 days or subdiaphragmatic vagotomy completely reversed the body weight gain and eliminated the increased adiponectin production and release in these rats, with reversal to a normal serum adiponectin level. Parasympathetic nerve activation by carbachol infusion for 5 days in rats increased serum adiponectin, with increased adiponectin production in visceral and subcutaneous adipose tissues without changes of body weight. These results demonstrate that activation of the parasympathetic nerve by VMH lesions stimulates production of adiponectin in visceral and subcutaneous adipose tissues and adiponectin release, resulting in elevated serum adiponectin. PMID:24487025

  7. 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 ...

  8. Circulating High-Molecular-Weight (HMW) Adiponectin Level Is Related with Breast Cancer Risk Better than Total Adiponectin: A Case-Control Study

    PubMed Central

    Guo, Ming-ming; Duan, Xue-ning; Cui, Shu-de; Tian, Fu-guo; Cao, Xu-chen; Geng, Cui-zhi; Fan, Zhi-min; Wang, Xiang; Wang, Shu; Jiang, Hong-chuan; Zhang, Jian-guo; Jin, Feng; Tang, Jin-hai; Liang, Hong; Yang, Zhen-lin; Wang, Hai-bo; Wang, Qi-tang; Li, Guo-lou; Li, Liang; Zhu, Shi-guang; Zuo, Wen-shu; Liu, Li-yuan; Wang, Lu; Ma, Dan-dan; Liu, Shu-chen; Xiang, Yu-juan; Liu, Lu; Ye, Chun-miao; Zhou, Wen-zhong; Wang, Fei; Yu, Li-xiang; Ma, Zhong-bing; Yu, Zhi-gang

    2015-01-01

    The level of total adiponectin, a mixture of different adiponectin forms, has been reported associated with breast cancer risk with inconsistent results. Whether the different forms play different roles in breast cancer risk prediction is unclear. To examine this, we measured total and high molecular weight (HMW) adiponectin in a case-control study (1167 sets). Higher circulating HMW adiponectin was negatively associated with breast cancer risk after adjusting for menopausal status and family history of breast cancer (P=0.024). We analyzed the relationship between adiponectin and breast cancer risk in 6 subgroups. Higher circulating HMW adiponectin was also negatively associated with breast cancer risk (P=0.020, 0.014, 0.035) in the subgroups of postmenopausal women, negative family history of breast cancer, BMI>=24.0. Total adiponectin was positively associated with breast cancer (P=0.028) in the subgroup of BMI<=24.0. Higher HMW/total adiponectin ratio was negatively associated with breast cancer (P=0.019) in the subgroup of postmenopausal women. Interestingly, in the subgroup of women with family history of breast cancer, higher circulating total and HMW adiponectin were positively associated with breast cancer risk (P=0.034, 0.0116). This study showed different forms of circulating adiponectin levels might play different roles in breast cancer risk. A higher circulating HMW adiponectin is associated with a decreased breast cancer risk, especially in postmenopausal, without family history of breast cancer or BMI>=24.0 subgroups, whereas higher circulating HMW adiponectin levels is a risk factor in women with a family history of breast cancer. Further investigation of different forms of adiponectin on breast cancer risk is needed. PMID:26070203

  9. Survivin upregulation, dependent on leptin-EGFR-Notch1 axis, is essential for leptin induced migration of breast carcinoma cells

    PubMed Central

    Knight, Brandi B.; Oprea-Ilies, Gabriela M.; Nagalingam, Arumugam; Yang, Lily; Cohen, Cynthia; Saxena, Neeraj K.; Sharma, Dipali

    2012-01-01

    Obese breast cancer patients exhibit a higher risk for larger tumor burden and increased metastasis. Molecular effects of obesity on carcinogenesis are mediated by autocrine and paracrine effects of adipocytokine leptin. Leptin participates in tumor progression and metastasis of human breast. We show that leptin induces clonogenicity and migration potential of breast cancer cells. We found that survivin expression is induced in response to leptin. In this study, we examine the role and leptin-mediated regulation of survivin. Leptin treatment leads to survivin upregulation, due in part to the activation of Notch1 and release of transcriptionally active Notch1-intracellular-domain (NICD). ChIP analysis show that NICD gets recruited to survivin promoter at CSL-binding-site in response to leptin treatment. Inhibition of Notch1 activity inhibits leptin-induced survivin upregulation. Leptin-induced transactivation of EGFR is involved in leptin-mediated Notch1 and survivin upregulation showing a novel upstream role of leptin-EGFR-Notch1 axis. We further show that leptin-induced migration of breast cancer cells requires survivin, as overexpression of survivin further increases, whereas silencing survivin abrogates leptin-induced migration. Using a pharmacological approach to inhibit survivin, we show that 3-hydroxy-3-methylglutaryl-coenzyme-A-reductase inhibitors (HRIs), lovastatin, can effectively inhibit leptin-induced survivin expression and migration. Importantly, leptin increased breast tumor growth in nude mice. These data show a novel role for survivin in leptin-induced migration and put forth pharmacological survivin inhibition as a potential novel therapeutic target. This conclusion is supported by in vivo data showing overexpression of leptin and survivin in epithelial cells of high grade ductal carcinoma in situ and high grade invasive carcinoma. PMID:21555376

  10. Leptin regulates bone formation via the sympathetic nervous system

    NASA Technical Reports Server (NTRS)

    Takeda, Shu; Elefteriou, Florent; Levasseur, Regis; Liu, Xiuyun; Zhao, Liping; Parker, Keith L.; Armstrong, Dawna; Ducy, Patricia; Karsenty, Gerard

    2002-01-01

    We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

  11. Promotion of melanoma growth by the metabolic hormone leptin.

    PubMed

    Ellerhorst, Julie A; Diwan, A H; Dang, Shyam M; Uffort, Deon G; Johnson, Marilyn K; Cooke, Carolyn P; Grimm, Elizabeth A

    2010-04-01

    We have previously shown that melanoma cells proliferate in response to the metabolic hormones TRH and TSH. The objective of the present study was to test the hypothesis that a third metabolic hormone, leptin, serves as a growth factor for melanoma. Using western blotting, indirect immunofluorescence, and RT-PCR, leptin receptors were found to be expressed by human melanoma cells. In contrast, cultured melanocytes expressed message for the receptor without detectable protein. Melanoma cells responded to treatment with leptin by activating the MAPK pathway and proliferating. Melanoma cells but not melanocytes, also expressed leptin protein, creating a potential autocrine loop. Examination of human melanoma tumors by immunohistochemistry revealed that melanomas and nevi expressed leptin at a high frequency. Melanomas also strongly expressed the leptin receptor, whereas nevi expressed this receptor to a much lesser degree. We conclude that leptin is a melanoma growth factor and that a leptin autocrine-loop may contribute to the uncontrolled proliferation of these cells. PMID:20204272

  12. The impact of leptin on perinatal development and psychopathology.

    PubMed

    Valleau, Jeanette C; Sullivan, Elinor L

    2014-11-01

    Leptin has long been associated with metabolism as it is a critical regulator of both food intake and energy expenditure, but recently, leptin dysregulation has been proposed as a mechanism of psychopathology. This review discusses the evidence supporting a role for leptin in mental health disorders and describes potential mechanisms that may underlie this association. Leptin plays a critical role in pregnancy and in fetal growth and development. Leptin's role and profile during development is examined in available human studies, and the validity of applying studies conducted in animal models to the human population are discussed. Rodents experience a postnatal leptin surge, which does not occur in humans or larger animal models. This suggests that further research using large mammal models, which have a leptin profile across pregnancy and development similar to humans, are of high importance. Maternal obesity and hyperleptinemia correlate with increased leptin levels in the umbilical cord, placenta, and fetus. Leptin levels are thought to impact fetal brain development; likely by activating proinflammatory cytokines that are known to impact many of the neurotransmitter systems that regulate behavior. Leptin is likely involved in behavioral regulation as leptin receptors are widely distributed in the brain, and leptin influences cortisol release, the mesoaccumbens dopamine pathway, serotonin synthesis, and hippocampal synaptic plasticity. In humans, both high and low levels of leptin are reported to be associated with psychopathology. This inconsistency is likely due to differences in the metabolic state of the study populations. Leptin resistance, which occurs in the obese state, may explain how both high and low levels of leptin are associated with psychopathology, as well as the comorbidity of obesity with numerous mental illnesses. Leptin resistance is likely to influence disorders such as depression and anxiety where high leptin levels have been correlated

  13. Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding.

    PubMed

    Kim, Jae Geun; Suyama, Shigetomo; Koch, Marco; Jin, Sungho; Argente-Arizon, Pilar; Argente, Jesús; Liu, Zhong-Wu; Zimmer, Marcelo R; Jeong, Jin Kwon; Szigeti-Buck, Klara; Gao, Yuanqing; Garcia-Caceres, Cristina; Yi, Chun-Xia; Salmaso, Natalina; Vaccarino, Flora M; Chowen, Julie; Diano, Sabrina; Dietrich, Marcelo O; Tschöp, Matthias H; Horvath, Tamas L

    2014-07-01

    We found that leptin receptors were expressed in hypothalamic astrocytes and that their conditional deletion led to altered glial morphology and synaptic inputs onto hypothalamic neurons involved in feeding control. Leptin-regulated feeding was diminished, whereas feeding after fasting or ghrelin administration was elevated in mice with astrocyte-specific leptin receptor deficiency. These data reveal an active role of glial cells in hypothalamic synaptic remodeling and control of feeding by leptin. PMID:24880214

  14. Inhibition of adipogenesis and leptin production in 3T3-L1 adipocytes by a derivative of meridianin C

    SciTech Connect

    Park, Yu-Kyoung; Lee, Tae-Yoon; Choi, Jong-Soon; Hong, Victor Sukbong; Lee, Jinho; Park, Jong-Wook; Jang, Byeong-Churl

    2014-10-03

    Highlights: • Compound 7b, a meridianin C derivative, inhibits adipogenesis. • Compound 7b inhibits C/EBP-α, PPAR-γ, FAS, STAT-3, and STAT-5 in 3T3-L1 adipocytes. • Compound 7b inhibits leptin, but not adiponectin, expression in 3T3-L1 adipocytes. • Compound 7b thus may have therapeutic potential against obesity. - Abstract: Meridianin C, a marine alkaloid, is a potent protein kinase inhibitor and has anti-cancer activity. We have recently developed a series of meridianin C derivatives (compound 7a–7j) and reported their proviral integration Moloney Murine Leukemia Virus (pim) kinases’ inhibitory and anti-proliferative effects on human leukemia cells. Here we investigated the effect of these meridianin C derivatives on adipogenesis. Strikingly, among the derivatives tested, compound 7b most strongly inhibited lipid accumulation during the differentiation of 3T3-L1 preadipocytes into adipocytes. However, meridianin C treatment was largely cytotoxic to 3T3-L1 adipocytes. On mechanistic levels, compound 7b reduced not only the expressions of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), and fatty acid synthase (FAS) but also the phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) and STAT-5 during adipocyte differentiation. Moreover, compound 7b repressed leptin, but not adiponectin, expression during adipocyte differentiation. Collectively, these findings demonstrate that a meridianin C derivative inhibits adipogenesis by down-regulating expressions and/or phosphorylations of C/EBP-α, PPAR-γ, FAS, STAT-3 and STAT-5.

  15. Development of second generation peptides modulating cellular adiponectin receptor responses

    NASA Astrophysics Data System (ADS)

    Otvos, Laszlo; Knappe, Daniel; Hoffmann, Ralf; Kovalszky, Ilona; Olah, Julia; Hewitson, Tim; Stawikowska, Roma; Stawikowski, Maciej; Cudic, Predrag; Lin, Feng; Wade, John; Surmacz, Eva; Lovas, Sandor

    2014-10-01

    The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC). In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML) cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399). The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM - low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400) was designed that counteracted 10-1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400) at similar concentrations will be an important target validation tool to study adiponectin functions.

  16. Development of second generation peptides modulating cellular adiponectin receptor responses

    PubMed Central

    Otvos, Laszlo; Knappe, Daniel; Hoffmann, Ralf; Kovalszky, Ilona; Olah, Julia; Hewitson, Tim D.; Stawikowska, Roma; Stawikowski, Maciej; Cudic, Predrag; Lin, Feng; Wade, John D.; Surmacz, Eva; Lovas, Sandor

    2014-01-01

    The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC). In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML) cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399). The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM—low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400) was designed that counteracted 10–1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400) at similar concentrations will be an important target validation tool to study adiponectin functions. PMID:25368867

  17. Strategies for the delivery of leptin to the CNS.

    PubMed

    Banks, William A; Lebel, Carl R

    2002-06-01

    Leptin is the major regulator of body fat. It is a 16 kD protein released by fat cells into the blood and crosses the blood-brain barrier (BBB) to interact with its receptors at the arcuate nucleus to affect feeding, thermogenesis, and other functions. Within normal and obese body weight ranges, serum and cerebrospinal fluid (CSF) levels of leptin directly correlate with body mass index and adiposity. In animals, leptin at high levels exerts effects on appetite and at low levels informs the brain when fat reserves are adequate to switch behavioral, endocrine, and immune functions from starvation mode. Leptin offers a unique therapeutic opportunity for conditions related to body weight control, such as reversal of obesity and anorexia, and as an indirect treatment for diseases related to being over- or under-weight, such as insulin resistant diabetes and the endocrine changes accompanying starvation. In humans and in many rodent models, obesity may be a consequence of leptin resistance. More specifically, resistance likely results from an impaired transport of leptin across the BBB. Peripheral administration of native leptin results in weight reduction in moderately obese individuals and weight loss and reversal of insulin resistance and dyslipidemia in individuals with low leptin levels. The peripheral pharmacokinetic and BBB transport characteristics of native leptin suggests strategies for improving the therapeutic profile of leptin. These strategies include the development of longer lasting and more permeable analogs, development of antagonists, enhancing the activity of the leptin transporter, and delivering leptin by intrathecal administration. PMID:12164378

  18. Obesity-related hypertension: is there a role for selective leptin resistance?

    PubMed

    Correia, Marcelo L G; Haynes, William G

    2004-06-01

    Obesity is a risk factor for cardiovascular diseases, in particular for hypertension. Serum leptin levels and sympathetic nerve activity are both increased in obesity. Leptin has been demonstrated to increase sympathetic nerve activity. Thus, leptin-dependent sympathoactivation might contribute to obesity-related hypertension. However, leptin resistance occurs in obesity. One possibility is that leptin resistance is selective to the metabolic effects of leptin, sparing its sympathoexcitatory actions. In this article, we review experimental evidence supporting the novel concept of selective leptin resistance. We also discuss the sympathetic actions of leptin that are relevant to blood pressure modulation and potential mechanisms of leptin resistance. Disruption of leptin intracellular signaling pathways and resistance of specific leptin-responsive neural networks provide theoretic models of selective leptin resistance. However, most information about leptin-sympathetic actions and leptin-resistance mechanisms derive from in vitro and animal studies. Future research in humans is widely awaited. PMID:15128477

  19. Hypothalamic PKA regulates leptin sensitivity and adiposity

    PubMed Central

    Yang, Linghai; McKnight, G. Stanley

    2015-01-01

    Mice lacking the RIIβ regulatory subunit of cyclic AMP-dependent protein kinase A (PKA) display reduced adiposity and resistance to diet-induced obesity. Here we show that RIIβ knockout (KO) mice have enhanced sensitivity to leptin's effects on both feeding and energy metabolism. After administration of a low dose of leptin, the duration of hypothalamic JAK/STAT3 signalling is increased, resulting in enhanced POMC mRNA induction. Consistent with the extended JAK/STAT3 activation, we find that the negative feedback regulator of leptin receptor signalling, Socs3, is inhibited in the hypothalamus of RIIβ KO mice. During fasting, RIIβ–PKA is activated and this correlates with an increase in CREB phosphorylation. The increase in CREB phosphorylation is absent in the fasted RIIβ KO hypothalamus. Selective inhibition of PKA activity in AgRP neurons partially recapitulates the leanness and resistance to diet-induced obesity of RIIβ KO mice. Our findings suggest that RIIβ–PKA modulates the duration of leptin receptor signalling and therefore the magnitude of the catabolic response to leptin. PMID:26381935

  20. Renaissance of leptin for obesity therapy.

    PubMed

    Quarta, Carmelo; Sánchez-Garrido, Miguel A; Tschöp, Matthias H; Clemmensen, Christoffer

    2016-05-01

    Diet-induced obesity and its metabolic comorbidities constitute an overwhelming health crisis and there is an urgent need for safe and effective pharmacological interventions. Being largely shelved for decades, scientists are now revisiting the anti-obesity virtues of leptin. Whereas it remains evident that leptin as a stand-alone therapy is not an effective approach, the potential for employing sensitising pharmacology to unleash the weight-lowering properties of leptin has injected new hope into the field. Fascinatingly, these leptin-sensitising agents seem to act via distinct metabolic pathways and may thus, in parallel with their clinical development, serve as important research tools to progress our understanding of the molecular, physiological and behavioural pathways underlying energy homeostasis and obesity pathophysiology. This review summarises a presentation given at the 'Is leptin coming back?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Thomas Meek and Gregory Morton, DOI: 10.1007/s00125-016-3898-3 , and by Gerald Shulman and colleagues, DOI: 10.1007/s00125-016-3909-4 ) and an overview by the Session Chair, Ulf Smith (DOI: 10.1007/s00125-016-3894-7 ). PMID:26983921

  1. The effect of Morus alba leaves extract and powder on resistin levels and liver transaminase enzymes activities in diabetes.

    PubMed

    Salemi, Z; Barzin Tond, S; Fallah, S; Shojaii, A; Seifi, M

    2016-01-01

    The current study was designed to investigate the changes of the resistin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels of diabetic rats after treatment with Morus alba leaves flavonoid extract (MLE) and Morus alba leaves powder (MLP). Thirty male wistar rats in five groups including control and diabetic groups were included. Diabetic groups consisted of diabetic control, sham and treated group with MLE and MLP. Type 2 diabetes was induced in rats by administration of streptozotocin (STZ) and - nicotinamide. The serum concentrations of resistin and insulin in the study groups were identified by ELISA. ALT and AST activities were assayed by spectrophotometer. For the first time, it was shown that the uptake of MLE and MLP by diabetic rats could significantly decrease the serum fasting blood sugar (FBS), resistin levels and enzymes activity of ALT and AST and increases the concentration of serum insulin significantly (P<0.05). in comparison with the sham group and diabetic control. The results showed that there was no significant difference between the anti-diabetic and inflammatory properties of MLE and MLP. In this study, the possible protective effect of MLE and MLP administration was evaluated against destructive effect of STZ on liver and pancreas function in diabetic rats. The results showed that these effects may play an important role in the regulating of adipokines secretion such as resistin and insulin secretion which are involved in the control of diabetes and obesity. MLE and MLP treatment could be useful agents in combination with other therapies in diabetes improvement. PMID:27262814

  2. Recombinant human FIZZ3/resistin stimulates lipolysis in cultured human adipocytes, mouse adipose explants, and normal mice.

    PubMed

    Ort, Tatiana; Arjona, Anibal A; MacDougall, John R; Nelson, Pam J; Rothenberg, Mark E; Wu, Frank; Eisen, Andrew; Halvorsen, Yuan-Di C

    2005-05-01

    Human FIZZ3 (hFIZZ3) was identified as an ortholog of mouse resistin (mResistin), an adipocyte-specific secreted factor linked to insulin resistance in rodents. Unlike mResistin, hFIZZ3 is expressed in macrophages and monocytes, but is undetectable in adipose tissue. The profound macrophage infiltration of adipose that occurs during obesity suggests that hFIZZ3 may play an important role in adipocyte biology. Using a recombinant protein produced in Escherichia coli, we report here that chronic treatment of cultured human adipocytes with hFIZZ3 results in hypotropic cells with smaller lipid droplets. Recombinant hFIZZ3 facilitates preadipocyte proliferation and stimulates adipocyte triglyceride lipolysis, whereas recombinant mResistin inhibits adipocyte differentiation, with no detectable effect on proliferation or lipolysis. In addition, insulin-stimulated glucose uptake and Akt phosphorylation are not altered in hFIZZ3-treated adipocytes, indicating an intact insulin response. In mouse adipose explants, hFIZZ3 accelerates simultaneously triglyceride lipolysis and fatty acid reesterification, as assessed by measurement of glycerol and fatty acid release. Consistent with the in vitro findings, acute administration of recombinant hFIZZ3 into normal mice caused a significant increase in serum glycerol concentration with no elevation in free fatty acid at 45 min post injection. Taken together, the data suggest that recombinant hFIZZ3 can influence adipose metabolism by regulating preadipocyte cell number, adipocyte lipid content, and energy expenditure via accelerating the fatty acid/triglyceride futile cycle. PMID:15705777

  3. The Impact of Leptin on Perinatal Development and Psychopathology

    PubMed Central

    Valleau, Jeanette C.; Sullivan, Elinor L.

    2014-01-01

    Leptin has long been associated with metabolism as it is a critical regulator of both food intake and energy expenditure, but recently, leptin dysregulation has been proposed as a mechanism of psychopathology. This review discusses the evidence supporting a role for leptin in mental health disorders and describes potential mechanisms that may underlie this association. Leptin plays a critical role in pregnancy and in fetal growth and development. Leptin’s role and profile during development is examined in available human studies and the validity of applying studies conducted in animal models to the human population are discussed. Rodents experience a postnatal leptin surge, which does not occur in humans or larger animal models. This suggests that further research using large mammal models, which have a leptin profile across pregnancy and development similar to humans, are of high importance. Maternal obesity and hyperleptinemia correlate with increased leptin levels in the umbilical cord, placenta, and fetus. Leptin levels are thought to impact fetal brain development; likely by activating proinflammatory cytokines that are known to impact many of the neurotransmitter systems that regulate behavior. Leptin is likely involved in behavioral regulation as leptin receptors are widely distributed in the brain, and leptin influences cortisol release, the mesoaccumbens dopamine pathway, serotonin synthesis, and hippocampal synaptic plasticity. In humans, both high and low levels of leptin are reported to be associated with psychopathology. This inconsistency is likely due to differences in the metabolic state of the study populations. Leptin resistance, which occurs in the obese state, may explain how both high and low levels of leptin are associated with psychopathology, as well as the comorbidity of obesity with numerous mental illnesses. Leptin resistance is likely to influence disorders such as depression and anxiety where both high and low leptin levels have been

  4. PPAR Agonist-Induced Reduction of Mcp1 in Atherosclerotic Plaques of Obese, Insulin-Resistant Mice Depends on Adiponectin-Induced Irak3 Expression

    PubMed Central

    Arnould, Thierry; Tsatsanis, Christos; Holvoet, Paul

    2013-01-01

    Synthetic peroxisome proliferator-activated receptor (PPAR) agonists are used to treat dyslipidemia and insulin resistance. In this study, we examined molecular mechanisms that explain differential effects of a PPARα agonist (fenofibrate) and a PPARγ agonist (rosiglitazone) on macrophages during obesity-induced atherogenesis. Twelve-week-old mice with combined leptin and LDL-receptor deficiency (DKO) were treated with fenofibrate, rosiglitazone or placebo for 12 weeks. Only rosiglitazone improved adipocyte function, restored insulin sensitivity, and inhibited atherosclerosis by decreasing lipid-loaded macrophages. In addition, it increased interleukin-1 receptor-associated kinase-3 (Irak3) and decreased monocyte chemoattractant protein-1 (Mcp1) expressions, indicative of a switch from M1 to M2 macrophages. The differences between fenofibrate and rosiglitazone were independent of Pparγ expression. In bone marrow-derived macrophages (BMDM), we identified the rosiglitazone-associated increase in adiponectin as cause of the increase in Irak3. Interestingly, the deletion of Irak3 in BMDM (IRAK3−/− BMDM) resulted in activation of the canonical NFκB signaling pathway and increased Mcp1 protein secretion. Rosiglitazone could not decrease the elevated Mcp1 secretion in IRAK3−/− BMDM directly and fenofibrate even increased the secretion, possibly due to increased mitochondrial reactive oxygen species production. Furthermore, aortic extracts of high-fat insulin-resistant LDL-receptor deficient mice, with lower adiponectin and Irak3 and higher Mcp1, showed accelerated atherosclerosis. In aggregate, our results emphasize an interaction between PPAR agonist-mediated increase in adiponectin and macrophage-associated Irak3 in the protection against atherosclerosis by PPAR agonists. PMID:23620818

  5. Transcriptional Characterization of Porcine Leptin and Leptin Receptor Genes.

    PubMed

    Pérez-Montarelo, Dafne; Fernández, Almudena; Barragán, Carmen; Noguera, Jose L; Folch, Josep M; Rodríguez, M Carmen; Ovilo, Cristina; Silió, Luis; Fernández, Ana I

    2013-01-01

    The leptin (LEP) and its receptor (LEPR) regulate food intake and energy balance through hypothalamic signaling. However, the LEP-LEPR axis seems to be more complex and its expression regulation has not been well described. In pigs, LEP and LEPR genes have been widely studied due to their relevance. Previous studies reported significant effects of SNPs located in both genes on growth and fatness traits. The aim of this study was to determine the expression profiles of LEP and LEPR across hypothalamic, adipose, hepatic and muscle tissues in Iberian x Landrace backcrossed pigs and to analyze the effects of gene variants on transcript abundance. To our knowledge, non porcine LEPR isoforms have been described rather than LEPRb. A short porcine LEPR isoform (LEPRa), that encodes a protein lacking the intracellular residues responsible of signal transduction, has been identified for the first time. The LEPRb isoform was only quantifiable in hypothalamus while LEPRa appeared widely expressed across tissues, but at higher levels in liver, suggesting that both isoforms would develop different roles. The unique LEP transcript showed expression in backfat and muscle. The effects of gene variants on transcript expression revealed interesting results. The LEPRc.1987C>T polymorphism showed opposite effects on LEPRb and LEPRa hypothalamic expression. In addition, one out of the 16 polymorphisms identified in the LEPR promoter region revealed high differential expression in hepatic LEPRa. These results suggest a LEPR isoform-specific regulation at tissue level. Conversely, non-differential expression of LEP conditional on the analyzed polymorphisms could be detected, indicating that its regulation is likely affected by other mechanisms rather than gene sequence variants. The present study has allowed a transcriptional characterization of LEP and LEPR isoforms on a range of tissues. Their expression patterns seem to indicate that both molecules develop peripheral roles apart from

  6. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels.

    PubMed

    Isidori, A M; Caprio, M; Strollo, F; Moretti, C; Frajese, G; Isidori, A; Fabbri, A

    1999-10-01

    Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8-55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU i.m.) was 30-40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced

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

    PubMed

    Anuradha; Krishna, Amitabh

    2014-09-01

    The aim of present study was to evaluate role of adiponectin in ovarian steroidogenesis during delayed embryonic development of Cynopterus sphinx. This study showed significantly low circulating adiponectin level and a decline in expression of adiponectin receptor 1 (AdipoR1) in the ovary during the period of delayed embryonic development as compared with the normal development. The adiponectin treatment in vivo during the period of delayed development caused significantly increased in circulating progesterone and estradiol levels together with increased expression of AdipoR1 in the ovary. The in vitro study confirmed the stimulatory effect of adiponectin on progesterone synthesis. Both in vivo and in vitro studies showed that the effects of adiponectin on ovarian steroidogenesis were mediated through increased expression of luteinizing hormone-receptor, steroidogenic acute regulatory protein and 3β-hydroxyl steroid dehydrogenase enzyme. The adiponectin treatment may also promote progesterone synthesis by modulating ovarian angiogenesis, cell survival and rate of apoptosis. PMID:24787661

  8. 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

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

    PubMed

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

    2016-01-01

    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

  10. Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels

    PubMed Central

    Kloiber, Stefan; Ripke, Stephan; Kohli, Martin A.; Reppermund, Simone; Salyakina, Daria; Uher, Rudolf; McGuffin, Peter; Perlis, Roy H.; Hamilton, Steven P.; Pütz, Benno; Hennings, Johannes; Brückl, Tanja; Klengel, Torsten; Bettecken, Thomas; Ising, Marcus; Uhr, Manfred; Dose, Tatjana; Unschuld, Paul G.; Zihl, Josef; Binder, Elisabeth; Müller-Myhsok, Bertram; Holsboer, Florian; Lucae, Susanne

    2013-01-01

    Leptin, a peptide hormone from adipose tissue and key player in weight regulation, has been suggested to be involved in sleep and cognition and to exert antidepressant-like effects, presumably via its action on the HPA-axis and hippocampal function. This led us to investigate whether genetic variants in the leptin gene, the level of leptin mRNA-expression and leptin serum concentrations are associated with response to antidepressant treatment. Our sample consisted of inpatients from the Munich Antidepressant Response Signature (MARS) project with weekly Hamilton Depression ratings, divided into two subsamples. In the exploratory sample (n=251) 17 single nucleotide polymorphisms (SNPs) covering the leptin gene region were genotyped. We found significant associations of several SNPs with impaired antidepressant treatment outcome and impaired cognitive performance after correction for multiple testing. The SNP (rs10487506) showing the highest association with treatment response (p=3.9 × 10−5) was analyzed in the replication sample (n=358) and the association could be verified (p=0.021) with response to tricyclic antidepressants. In an additional meta-analysis combining results from the MARS study with data from the Genome-based Therapeutic Drugs for Depression (GENDEP) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies, nominal associations of several polymorphisms in the upstream vicinity of rs10487506 with treatment outcome were detected (p=0.001). In addition, we determined leptin mRNA expression in lymphocytes and leptin serum levels in subsamples of the MARS study. Unfavorable treatment outcome was accompanied with decreased leptin mRNA and leptin serum levels. Our results suggest an involvement of leptin in antidepressant action and cognitive function in depression with genetic polymorphisms in the leptin gene, decreased leptin gene expression and leptin deficiency in serum being risk factors for resistance to antidepressant

  11. Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels.

    PubMed

    Kloiber, Stefan; Ripke, Stephan; Kohli, Martin A; Reppermund, Simone; Salyakina, Daria; Uher, Rudolf; McGuffin, Peter; Perlis, Roy H; Hamilton, Steven P; Pütz, Benno; Hennings, Johannes; Brückl, Tanja; Klengel, Torsten; Bettecken, Thomas; Ising, Marcus; Uhr, Manfred; Dose, Tatjana; Unschuld, Paul G; Zihl, Josef; Binder, Elisabeth; Müller-Myhsok, Bertram; Holsboer, Florian; Lucae, Susanne

    2013-07-01

    Leptin, a peptide hormone from adipose tissue and key player in weight regulation, has been suggested to be involved in sleep and cognition and to exert antidepressant-like effects, presumably via its action on the HPA-axis and hippocampal function. This led us to investigate whether genetic variants in the leptin gene, the level of leptin mRNA-expression and leptin serum concentrations are associated with response to antidepressant treatment. Our sample consisted of inpatients from the Munich Antidepressant Response Signature (MARS) project with weekly Hamilton Depression ratings, divided into two subsamples. In the exploratory sample (n=251) 17 single nucleotide polymorphisms (SNPs) covering the leptin gene region were genotyped. We found significant associations of several SNPs with impaired antidepressant treatment outcome and impaired cognitive performance after correction for multiple testing. The SNP (rs10487506) showing the highest association with treatment response (p=3.9×10(-5)) was analyzed in the replication sample (n=358) and the association could be verified (p=0.021) with response to tricyclic antidepressants. In an additional meta-analysis combining results from the MARS study with data from the Genome-based Therapeutic Drugs for Depression (GENDEP) and the Sequenced Treatment Alternatives to Relieve Depression (STAR(⁎)D) studies, nominal associations of several polymorphisms in the upstream vicinity of rs10487506 with treatment outcome were detected (p=0.001). In addition, we determined leptin mRNA expression in lymphocytes and leptin serum levels in subsamples of the MARS study. Unfavorable treatment outcome was accompanied with decreased leptin mRNA and leptin serum levels. Our results suggest an involvement of leptin in antidepressant action and cognitive function in depression with genetic polymorphisms in the leptin gene, decreased leptin gene expression and leptin deficiency in serum being risk factors for resistance to antidepressant

  12. Expression and immunohistochemical localization of leptin in human periapical granulomas

    PubMed Central

    Martín-González, Jénifer; Carmona-Fernández, Antonio; Pérez-Pérez, Antonio; Sánchez-Jiménez, Flora; Sánchez-Margalet, Víctor

    2015-01-01

    Background Leptin, initially described as an adipocyte-derived hormone to regulate weight control, is expressed in normal and inflamed human dental pulp, being up-regulated during pulp experimental inflammation. Leptin receptor (LER) has been identified in human periapical granulomas. The aim of this study was to analyze and characterize the expression of leptin in human periapical granulomas. Material and Methods Fifteen periapical inflammatory lesions were obtained from extracted human teeth and teeth which underwent periapical surgery. After their morphological categorization as periapical granulomas and gradation of the inflammatory infiltrate, they were examined by immunohistochemistry using human leptin policlonal antibodies. Leptin mRNA expression was also determined by quantitative real-time PCR (qRT-PCR) and the amount of leptin protein was analyzed by immunoblot. Results All periapical lesions exhibited the characteristic of chronic granulomatous inflammatory process with inflammatory infiltrate grade III. Leptin+ cells were detected in 13 periapical granulomas (86.6%). The median number of Leptin+ cells in periapical granulomas was 1.70 (0.00-7.4). Amongst the inflammatory cells in the periapical granulomas, only macrophages were reactive to leptin antibodies. Western blot analysis revealed the presence in all samples of a protein with apparent molecular weight of approximately 16 kDa, corresponding to the estimated molecular weights of leptin. The expression of leptin mRNA was confirmed by qRT-PCR analysis and the size of the amplified fragment (296 bp for leptin and 194 bp for cyclophilin) was assessed by agarose gel electrophoresis. Conclusions For the first time, it has been demonstrated that human periapical granuloma expresses the adipokine leptin. Key words: Apical granuloma, dental pulp, endodontics, leptin, leptin receptor, immune system, immunohistochemistry, periapical inflammatory response. PMID:25662559

  13. Hair cycle control by leptin as a new anagen inducer.

    PubMed

    Sumikawa, Yasuyuki; Inui, Shigeki; Nakajima, Takeshi; Itami, Satoshi

    2014-01-01

    Our purpose is to clarify the physiological role of leptin in hair cycle as leptin reportedly causes activation of Stat3, which is indispensable for hair cycling. While hair follicles in dorsal skin of 5-week-old C57/BL6 mice had progressed to late anagen phase, those in dorsal skin of 5-week-old leptin receptor deficient db/db mice remained in the first telogen and later entered the anagen at postnatal day 40, indicating that deficiency in leptin receptor signalling delayed the second hair cycle progression. Next, we shaved dorsal hairs on wild-type mice at postnatal 7 weeks and injected skin with mouse leptin or a mock. After 20 days, although mock injection showed no effect, hair growth occurred around leptin injection area. Human leptin fragment (aa22-56) had similar effects. Although the hair cycle of ob/ob mice was similar to that of wild-type mice, injection of mouse leptin on ob/ob mice at postnatal 7 weeks induced anagen transition. Immunohistochemically, leptin is expressed in hair follicles from catagen to early anagen in wild-type mice, suggesting that leptin is an anagen inducer in vivo. Phosphorylation of Erk, Jak2 and Stat3 in human keratinocytes was stimulated by leptin and leptin fragment. In addition, RT-PCR and ELISA showed that the production of leptin by human dermal papilla cells increased under hypoxic condition, suggesting that hypoxia in catagen/telogen phase promotes leptin production, preparing for entry into the next anagen. In conclusion, leptin, a well-known adipokine, acts as an anagen inducer and represents a new player in hair biology. PMID:24237265

  14. Role of leptin in female reproduction.

    PubMed

    Pérez-Pérez, Antonio; Sánchez-Jiménez, Flora; Maymó, Julieta; Dueñas, José L; Varone, Cecilia; Sánchez-Margalet, Víctor

    2015-01-01

    Reproductive function is dependent on energy resources. The role of weight, body composition, fat distribution and the effect of diet have been largely investigated in experimental female animals as well as in women. Any alteration in diet and/or weight may induce abnormalities in timing of sexual maturation and fertility. However, the cellular mechanisms involved in the fine coordination of energy balance and reproduction are largely unknown. The brain and hypothalamic structures receive endocrine and/or metabolic signals providing information on the nutritional status and the degree of fat stores. Adipose tissue acts both as a store of energy and as an active endocrine organ, secreting a large number of biologically important molecules termed adipokines. Adipokines have been shown to be involved in regulation of the reproductive functions. The first adipokine described was leptin. Extensive research over the last 10 years has shown that leptin is not only an adipose tissue-derived messenger of the amount of energy stores to the brain, but also a crucial hormone/cytokine for a number of diverse physiological processes, such as inflammation, angiogenesis, hematopoiesis, immune function, and most importantly, reproduction. Leptin plays an integral role in the normal physiology of the reproductive system with complex interactions at all levels of the hypothalamic-pituitary gonadal (HPG) axis. In addition, leptin is also produced by placenta, where it plays an important autocrine function. Observational studies have demonstrated that states of leptin excess, deficiency, or resistance can be associated with abnormal reproductive function. This review focuses on the leptin action in female reproduction. PMID:25014521

  15. Adiponectin downregulation is associated with volume overload-induced myocyte dysfunction in rats

    PubMed Central

    Wang, Li-li; Miller, Dori; Wanders, Desiree; Nanayakkara, Gayani; Amin, Rajesh; Judd, Robert; Morrison, Edward E; Zhong, Ju-ming

    2016-01-01

    Aim: Adiponectin has been reported to exert protective effects during pathological ventricular remodeling, but the role of adiponectin in volume overload-induced heart failure remains unclear. In this study we investigated the effect of adiponectin on cardiac myocyte contractile dysfunction following volume overload in rats. Methods: Volume overload was surgically induced in rats by infrarenal aorta-vena cava fistula. The rats were intravenously administered adenoviral adiponectin at 2-, 6- and 9-weeks following fistula. The protein expression of adiponectin, adiponectin receptors (AdipoR1/R2 and T-cadherin) and AMPK activity were measured using Western blot analyses. Isolated ventricular myocytes were prepared at 12 weeks post-fistula to examine the contractile performance of myocytes and intracellular Ca2+ transient. Results: A-V fistula resulted in significant reductions in serum and myocardial adiponectin levels, myocardial adiponectin receptor (AdipoR1/R2 and T-cadherin) levels, as well as myocardial AMPK activity. Consistent with these changes, the isolated myocytes exhibited significant depression in cell shortening and intracellular Ca2+ transient. Administration of adenoviral adiponectin significantly increased serum adiponectin levels and prevented myocyte contractile dysfunction in fistula rats. Furthermore, pretreatment of isolated myocytes with recombinant adiponectin (2.5 μg/mL) significantly improved their contractile performance in fistula rats, but had no effects in control or adenoviral adiponectin-administered rats. Conclusion: These results demonstrate a positive correlation between adiponectin downregulation and volume overload-induced ventricular remodeling. Adiponectin plays a protective role in volume overload-induced heart failure. PMID:26616727

  16. 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. PMID:23261955

  17. Resistin-induced stromal cell-derived factor-1 expression through Toll-like receptor 4 and activation of p38 MAPK/ NFκB signaling pathway in gastric cancer cells

    PubMed Central

    2014-01-01

    Background Stromal cell-derived factor-1 (SDF-1) (CXC chemokine ligand-12)/CXC chemokine receptor 4 (CXCR4) is involved in the carcinogenesis of human gastric cancer, where it stimulates angiogenesis and favors metastasis of tumor cells to distant organs. In addition, resistin is suggested to be an important link between obesity and the development of gastric cancer. Resistin has identified as an important player in inflammatory responses, and emerged as a mediator in inflammation-associated cancer. A limited number of studies have investigated the association of resistin and SDF-1 with gastric cancer. Herein, we investigated the molecular mechanisms by which resistin influences the expression of SDF-1 in gastric carcinoma cells. Results Human gastric cancer cell lines were exposed to doses of resistin; SDF-1 expression and secretion levels were then determined. Real-time polymerase chain reaction and western blotting analyses were performed to clarify molecular changes. Inhibition of Toll-like receptor 4 (TLR4) by a competitive antagonist inhibited resistin-induced SDF-1 expression. Pharmacological inhibitors and small interfering RNA (siRNA) demonstrated that activation of the p38 mitogen-activated protein kinase (MAPK) pathway is critical for resistin-induced SDF-1 expression mediated by TLR4. The promoter activity and transcription factor enzyme-linked immunosorbent assay revealed that resistin induced expression of SDF-1 mediated by NF-κB in gastric cancer cells. Inhibition of p38 MARK activation blocked the SDF-1-induced expression and the SDF-1 promoter activity in the cancer gastric cells. Chromatin immunoprecipitation assay revealed that inhibition of p38 MARK activation also blocked the resistin-increased NF-κB-DNA-binding activity. Conclusions Resistin-induced SDF-1 upregulation by activation of TLR4, p38 MARK and NF-κB may explain a new role of resistin in the link of obesity and gastric cancer. PMID:24929539

  18. 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

  19. Comparative endocrinology of leptin: Assessing function in a phylogenetic context

    PubMed Central

    Londraville, Richard L.; Macotela, Yazmin; Duff, Robert J.; Easterling, Marietta R.; Liu, Qin; Crespi, Erica J.

    2014-01-01

    As we approach the end of two decades of leptin research, the comparative biology of leptin is just beginning. We now have several leptin orthologs described from nearly every major clade among vertebrates, and are moving beyond gene descriptions to functional studies. Even at this early stage, it is clear that non-mammals display clear functional similarities and differences with their better-studied mammalian counterparts. This review assesses what we know about leptin function in mammals and non-mammals, and gives examples of how these data can inform leptin biology in humans. PMID:24525452

  20. Duplicated Leptin Receptors in Two Species of Eel Bring New Insights into the Evolution of the Leptin System in Vertebrates

    PubMed Central

    Morini, Marina; Pasquier, Jérémy; Dirks, Ron; van den Thillart, Guido; Tomkiewicz, Jonna; Rousseau, Karine; Dufour, Sylvie; Lafont, Anne-Gaëlle

    2015-01-01

    Since its discovery in mammals as a key-hormone in reproduction and metabolism, leptin has been identified in an increasing number of tetrapods and teleosts. Tetrapods possess only one leptin gene, while most teleosts possess two leptin genes, as a result of the teleost third whole genome duplication event (3R). Leptin acts through a specific receptor (LEPR). In the European and Japanese eels, we identified two leptin genes, and for the first time in vertebrates, two LEPR genes. Synteny analyses indicated that eel LEPRa and LEPRb result from teleost 3R. LEPRb seems to have been lost in the teleost lineage shortly after the elopomorph divergence. Quantitative PCRs revealed a wide distribution of leptins and LEPRs in the European eel, including tissues involved in metabolism and reproduction. Noticeably, leptin1 was expressed in fat tissue, while leptin2 in the liver, reflecting subfunctionalization. Four-month fasting had no impact on the expression of leptins and LEPRs in control European eels. This might be related to the remarkable adaptation of silver eel metabolism to long-term fasting throughout the reproductive oceanic migration. In contrast, sexual maturation induced differential increases in the expression of leptins and LEPRs in the BPG-liver axis. Leptin2 was strikingly upregulated in the liver, the central organ of the reproductive metabolic challenge in teleosts. LEPRs were differentially regulated during sexual maturation, which may have contributed to the conservation of the duplicated LEPRs in this species. This suggests an ancient and positive role of the leptin system in the vertebrate reproductive function. This study brings new insights on the evolutionary history of the leptin system in vertebrates. Among extant vertebrates, the eel represents a unique case of duplicated leptins and leptin receptors as a result of 3R. PMID:25946034

  1. Duplicated leptin receptors in two species of eel bring new insights into the evolution of the leptin system in vertebrates.

    PubMed

    Morini, Marina; Pasquier, Jérémy; Dirks, Ron; van den Thillart, Guido; Tomkiewicz, Jonna; Rousseau, Karine; Dufour, Sylvie; Lafont, Anne-Gaëlle

    2015-01-01

    Since its discovery in mammals as a key-hormone in reproduction and metabolism, leptin has been identified in an increasing number of tetrapods and teleosts. Tetrapods possess only one leptin gene, while most teleosts possess two leptin genes, as a result of the teleost third whole genome duplication event (3R). Leptin acts through a specific receptor (LEPR). In the European and Japanese eels, we identified two leptin genes, and for the first time in vertebrates, two LEPR genes. Synteny analyses indicated that eel LEPRa and LEPRb result from teleost 3R. LEPRb seems to have been lost in the teleost lineage shortly after the elopomorph divergence. Quantitative PCRs revealed a wide distribution of leptins and LEPRs in the European eel, including tissues involved in metabolism and reproduction. Noticeably, leptin1 was expressed in fat tissue, while leptin2 in the liver, reflecting subfunctionalization. Four-month fasting had no impact on the expression of leptins and LEPRs in control European eels. This might be related to the remarkable adaptation of silver eel metabolism to long-term fasting throughout the reproductive oceanic migration. In contrast, sexual maturation induced differential increases in the expression of leptins and LEPRs in the BPG-liver axis. Leptin2 was strikingly upregulated in the liver, the central organ of the reproductive metabolic challenge in teleosts. LEPRs were differentially regulated during sexual maturation, which may have contributed to the conservation of the duplicated LEPRs in this species. This suggests an ancient and positive role of the leptin system in the vertebrate reproductive function. This study brings new insights on the evolutionary history of the leptin system in vertebrates. Among extant vertebrates, the eel represents a unique case of duplicated leptins and leptin receptors as a result of 3R. PMID:25946034

  2. The Effects of Leptin Replacement on Neural Plasticity

    PubMed Central

    Paz-Filho, Gilberto J.

    2016-01-01

    Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intra- and extrahypothalamic areas, including the hippocampus. Furthermore, in one of those patients, improvements in neurocognitive development have been observed. In addition to this evidence linking leptin to neural plasticity and function, observational studies evaluating leptin-sufficient humans have also demonstrated direct correlation between blood leptin levels and brain volume and inverse associations between circulating leptin and risk for the development of dementia. This review summarizes the evidence in the literature on the role of leptin in neural plasticity (in leptin-deficient and in leptin-sufficient individuals) and its effects on synaptic activity, glutamate receptor trafficking, neuronal morphology, neuronal development and survival, and microglial function. PMID:26881138

  3. The Diagnostic Role of Adiponectin in Pulmonary Embolism

    PubMed Central

    Gul, Evrim; Gul, Yeliz; Pepele, Mustafa Safa; Yıldız, Mustafa; Bozdemir, Mehmet Nuri; Onur, Mehmet Ruhi; Mutlu, Bengü; Yıldız, Feti; Alataş, Ömer Doğan; İlhan, Necip

    2016-01-01

    Background and Aims. Pulmonary thromboembolism (PTE) is a frequent disease with difficult diagnosis and high mortality. Misdiagnosis occurs in 2/3 patients and mortality rates reach up to 30%. The aim of our study was to investigate the role of adiponectin used in emergency service in diagnosis of PTE. Materials and Methods. 95 patients with suspected PTE included in the study. Plasma adiponectin and D-dimer levels were measured and chest X-ray and multidetector row computed tomography scan obtained. Diagnosis was supported by vascular filling defect on tomography. Control group consisted of patients with suspected PTE and normal chest computed tomography findings. Results. Mean D-dimer level was 4241.66 ± 1082.98 ng/mL in patients and 2211.21 ± 1765.53 ng/mL in the control group (p ≤ 0.05). Mean adiponectin level was 5.46 ± 4.39 μg/mL in patients and 7.68 ± 4.67 μg/mL in the control group (p ≤ 0.05). Wells and Geneva scores were higher in patients compared to the control group. Conclusions. As a result, we conclude that lower adiponectin levels have an important role in the diagnosis of PTE. PMID:27042667

  4. ASSOCIATION BETWEEN ADIPONECTIN, INSULIN RESISTANCE, AND ENDOMETRIAL CANCER

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Obesity is a well-known risk factor for the development of endometrial cancer; however, weight alone does not account for all cases. The authors hypothesized that insulin resistance also contributes to an increased risk for endometrial cancer. Adiponectin is a protein secreted by adipose...

  5. Leptin: a novel therapeutic strategy for Alzheimer's disease.

    PubMed

    Tezapsidis, Nikolaos; Johnston, Jane M; Smith, Mark A; Ashford, J Wesson; Casadesus, Gemma; Robakis, Nikolaos K; Wolozin, Benjamin; Perry, George; Zhu, Xiongwei; Greco, Steven J; Sarkar, Sraboni

    2009-01-01

    Adipocyte-derived leptin appears to regulate a number of features defining Alzheimer's disease (AD) at the molecular and physiological level. Leptin has been shown to reduce the amount of extracellular amyloid beta, both in cell culture and animal models, as well as to reduce tau phosphorylation in neuronal cells. Importantly, chronic administration of leptin resulted in a significant improvement in the cognitive performance of transgenic animal models. In AD, weight loss often precedes the onset of dementia and the level of circulating leptin is inversely proportional to the severity of cognitive decline. It is speculated that a deficiency in leptin levels or function may contribute to systemic and CNS abnormalities leading to disease progression. Furthermore, a leptin deficiency may aggravate insulin-controlled pathways, known to be aberrant in AD. These observations suggest that a leptin replacement therapy may be beneficial for these patients. PMID:19387109

  6. Astrocyte Leptin Receptor (ObR) and Leptin Transport in Adult-Onset Obese Mice

    PubMed Central

    Pan, Weihong; Hsuchou, Hung; He, Yi; Sakharkar, Amul; Cain, Courtney; Yu, Chuanhui; Kastin, Abba J.

    2008-01-01

    The agouti viable yellow (Avy) spontaneous mutation generates an unusual mouse phenotype of agouti-colored coat and adult-onset obesity with metabolic syndrome. Persistent production of agouti signaling protein in Avy mice antagonizes melanocortin receptors in the hypothalamus. To determine how this disruption of neuroendocrine circuits affects leptin transport across the blood-brain barrier (BBB), we measured leptin influx in Avy and B6 control mice after the development of obesity, hyperleptinemia, and increased adiposity. After iv bolus injection, 125I-leptin crossed the BBB significantly faster in young (2 month old) B6 mice than in young Avy mice or in older (8 month old) mice of either strain. This difference was not observed by in situ brain perfusion studies, indicating the cause being circulating factors, such as elevated leptin levels or soluble receptors. Thus, Avy mice showed peripheral leptin resistance. ObRa, the main transporting receptor for leptin at the BBB, showed no change in mRNA expression in the cerebral microvessels between the age-matched (2 month old) Avy and B6 mice. Higher ObRb mRNA was seen in the Avy microvasculature with unknown significance. Immunofluorescent staining unexpectedly revealed that many of the ObR(+) cells were astrocytes and that the Avy mice showed significantly more ObR(+) astrocytes in the hypothalamus than the B6 mice. Although leptin permeation from the circulation was slower in the Avy mice, the increased ObR expression in astrocytes and increased ObRb mRNA in microvessels suggest the possibility of heightened central nervous system sensitivity to circulating leptin. PMID:18292187

  7. Genetic variations of leptin and leptin receptor are associated with body composition changes in response to physical training.

    PubMed

    Huuskonen, Antti; Lappalainen, Jani; Tanskanen, Minna; Oksala, Niku; Kyröläinen, Heikki; Atalay, Mustafa

    2010-06-01

    Leptin regulates body weight, metabolism, and tissue adaptations to environmental stressors. We examined the association of single nucleotide polymorphism (SNP) of leptin promoter G-2548A (rs7799039) and leptin receptor Gln223Arg (rs1137101) with body composition, plasma leptin levels, and peak oxygen uptake (VO(2)peak) in response to 8 weeks of physical training in 48 male military conscripts. AA homozygotes of leptin promoter SNP-2548 showed higher body fat and BMI values than G allele carriers. Acute exercise decreased leptin levels in G allele carriers, but increased in AA homozygotes. Physical training significantly decreased BMI values and also a tendency for decreased plasma leptin levels was observed in all subjects. In G allele carriers, BMI loss was mainly due to decreased fat mass, whereas in AA homozygotes due to loss of fat-free mass. Training increased VO(2)peak in all subjects with most prominent effects in G allele carriers. Regarding leptin receptor SNP, there were no statistically significant differences in BMI values between the genotype groups at baseline or after physical training. Our results suggest that physical training-induced alterations in body composition and plasma leptin may be influenced by a genetic variation of leptin promoter but not of leptin receptor. PMID:20517895

  8. Leptin promotes proliferation and metastasis of human gallbladder cancer through OB-Rb leptin receptor.

    PubMed

    Zou, Hao; Liu, Yunxia; Wei, Dong; Wang, Tao; Wang, Kun; Huang, Songquan; Liu, Lixin; Li, Yuehua; Ge, Jiayun; Li, Xiao; Zhu, Hong; Wang, Lianmin; Zhao, Songling; Zhang, Xiaowen; Wang, Lin

    2016-07-01

    Emerging evidence has shown that leptin, an adipocyte-derived cytokine that is closely associated with obesity, play a significant role in carcinogenesis and tumorigenesis. However, its impact on gallbladder cancer (GBC) remains unclear. In this study, we firstly found that leptin and its functional receptor OB-Rb were significantly co-expressed in human GBC tissues and cell lines, the content of which were higher than those in normal human gallbladder tissues. Treatment with leptin promoted the proliferation, migration and invasion of GBC cells, which were attenuated by OB-Rb shRNA. Blocking in the G2/M period of cell cycle, increasing of MMP3 and MMP9, increasing of VEGF-C/D, activation of SOCS3/JAK2/p-STAT3 pathway was demonstrated after treatment with leptin. All of these positive responses were attenuated by OB-Rb receptor shRNA. Taken together, our findings suggest that leptin promoted the proliferation, migration and invasion of GBC cells by increasing OB-Rb expression through the SOCS3/JAK2/p-STAT3 signal pathway. Targeting the leptin/OB-Rb axis could be an attractive therapeutic strategy for treatment of GBC. PMID:27211817

  9. Rapamycin Normalizes Serum Leptin by Alleviating Obesity and Reducing Leptin Synthesis in Aged Rats.

    PubMed

    Scarpace, Philip J; Matheny, Michael; Strehler, Kevin Y E; Toklu, Hale Zerrin; Kirichenko, Nataliya; Carter, Christy S; Morgan, Drake; Tümer, Nihal

    2016-07-01

    This investigation examines whether a low intermittent dose of rapamycin will avoid the hyperlipidemia and diabetes-like syndrome associated with rapamycin while still decreasing body weight and adiposity in aged obese rats. Furthermore, we examined if the rapamycin-mediated decrease in serum leptin was a reflection of decreased adiposity, diminished leptin synthesis, or both. To these ends, rapamycin (1mg/kg) was administered three times a week to 3 and 24-month old rats. Body weight, food intake, body composition, mTORC1 signaling, markers of metabolism, as well as serum leptin levels and leptin synthesis in adipose tissue were examined and compared to that following a central infusion of rapamycin. Our data suggest that the dosing schedule of rapamycin acts on peripheral targets to inhibit mTORC1 signaling, preferentially reducing adiposity and sparing lean mass in an aged model of obesity resulting in favorable outcomes on blood triglycerides, increasing lean/fat ratio, and normalizing elevated serum leptin with age. The initial mechanism underlying the rapamycin responses appears to have a peripheral action and not central. The peripheral rapamycin responses may communicate an excessive nutrients signal to the hypothalamus that triggers an anorexic response to reduce food consumption. This coupled with potential peripheral mechanism serves to decrease adiposity and synthesis of leptin. PMID:25617379

  10. Association of Adiponectin Polymorphism with Metabolic Syndrome Risk and Adiponectin Level with Stroke Risk: A Meta-Analysis.

    PubMed

    Yuan, Hui-Ping; Sun, Liang; Li, Xing-Hui; Che, Fu-Gang; Zhu, Xiao-Quan; Yang, Fan; Han, Jing; Jia, Chun-Yuan; Yang, Ze

    2016-01-01

    Many previous studies have provided evidence that the ADIPOQ +45T>G polymorphism (rs2241766) might cause metabolic syndrome (MS). As a cardiovascular manifestation of MS, the incidence of stroke is associated with adiponectin; however, the results remain controversial and inconsistent. Systematic searches of relevant studies published up to Dec 2014 and Jan 2016 on the ADIPOQ +45T>G polymorphism and the risk of MS and adiponectin levels and the risk of stroke, respectively, were conducted in MEDLINE and EMBASE. The odds ratio (OR) or risk ratio (RR) and their 95% confidence interval (95% CI) were extracted. Sixteen studies containing 4,113 MS cases and 3,637 healthy controls indicated a weak positive association between ADIPOQ +45 T>G and MS in the dominant genetic model (OR = 1.30, 95% CI = 1.03-1.65), which was also validated by stratified subgroup analyses. Twelve studies including 26,213 participants and 4,246 stroke cases indicated that 5 μg/ml increments in adiponectin level were not relevant to stroke risk (RR = 1.05, 95% CI = 1.00-1.10, P = 0.069). This study suggested a weak positive association of ADIPOQ +45T>G with MS and a strong association with metabolic-related disease. Additionally, adiponectin level was not a causal factor of increasing stroke risk. PMID:27578536

  11. Association of Adiponectin Polymorphism with Metabolic Syndrome Risk and Adiponectin Level with Stroke Risk: A Meta-Analysis

    PubMed Central

    Yuan, Hui-Ping; Sun, Liang; Li, Xing-Hui; Che, Fu-Gang; Zhu, Xiao-Quan; Yang, Fan; Han, Jing; Jia, Chun-Yuan; Yang, Ze

    2016-01-01

    Many previous studies have provided evidence that the ADIPOQ +45T>G polymorphism (rs2241766) might cause metabolic syndrome (MS). As a cardiovascular manifestation of MS, the incidence of stroke is associated with adiponectin; however, the results remain controversial and inconsistent. Systematic searches of relevant studies published up to Dec 2014 and Jan 2016 on the ADIPOQ +45T>G polymorphism and the risk of MS and adiponectin levels and the risk of stroke, respectively, were conducted in MEDLINE and EMBASE. The odds ratio (OR) or risk ratio (RR) and their 95% confidence interval (95% CI) were extracted. Sixteen studies containing 4,113 MS cases and 3,637 healthy controls indicated a weak positive association between ADIPOQ +45 T>G and MS in the dominant genetic model (OR = 1.30, 95% CI = 1.03–1.65), which was also validated by stratified subgroup analyses. Twelve studies including 26,213 participants and 4,246 stroke cases indicated that 5 μg/ml increments in adiponectin level were not relevant to stroke risk (RR = 1.05, 95% CI = 1.00–1.10, P = 0.069). This study suggested a weak positive association of ADIPOQ +45T>G with MS and a strong association with metabolic-related disease. Additionally, adiponectin level was not a causal factor of increasing stroke risk. PMID:27578536

  12. Relationships between plasma leptin levels, leptin G2548A, leptin receptor Gln223Arg polymorphisms and gestational diabetes mellitus in Chinese population

    PubMed Central

    Yang, Mei; Peng, Songxu; Li, Wei; Wan, Zhihua; Fan, Linlin; Du, Yukai

    2016-01-01

    The purposes of this study were to examine concentrations of leptin and biochemical parameters in gestational diabetes mellitus (GDM) patients and normal glucose tolerance (NGT) individuals, and also to explore the links of leptin (LEP) G2548A and leptin receptor (LEPR) Gln223Arg polymorphisms with leptin levels and GDM risk among Chinese. Our study included 357 GDM and 355 NGT individuals who were at 24~30 gestational weeks. Plasma leptin and insulin levels were analyzed by ELISA. Gene polymorphisms were genotyped using TaqMan real-time polymerase chain reaction assay. The results showed that plasma leptin levels were significantly higher in the impaired fasting glucose (IFG) group than NGT group (34.35 (26.54, 56.48) ng/mL vs 26.31 (17.99, 37.87) ng/mL, P < 0.05). Plasma leptin levels correlated with plasma fasting insulin levels, pre-pregnant body mass index, homeostasis model assessment-insulin resistance and quantitative insulin sensitivity check index both in GDM and NGT group (P < 0.05). However, neither LEP G2548A nor LEPR Gln223Arg polymorphisms were significantly associated with GDM risk and plasma leptin levels (P > 0.05). Our findings showed that high leptin level was associated with GDM. And larger and more rigorous researches were needed to further explore the association of LEP and LEPR gene polymorphisms and GDM among Chinese population. PMID:27034205

  13. Determinants of serum adiponectin in persons with and without type 1 diabetes.

    PubMed

    Maahs, David M; Ogden, Lorraine G; Snell-Bergeon, Janet K; Kinney, Gregory L; Wadwa, R Paul; Hokanson, John E; Dabelea, Dana; Kretowski, Adam; Eckel, Robert H; Rewers, Marian

    2007-09-15

    Low levels of adiponectin have been related to coronary heart disease, but adiponectin is higher in persons with type 1 diabetes who have an increased rate of coronary disease. In the Coronary Artery Calcification in Type 1 Diabetes Study (2000-2002), the authors investigated potential determinants of elevated adiponectin levels in persons with type 1 diabetes and whether a difference exists compared with nondiabetic persons. Serum adiponectin was measured in 1,393 persons (sex: 48% male; age: 38 (standard deviation: 9) years; diabetes duration: 23 (standard deviation: 9) years; 54% nondiabetic and 46% with type 1 diabetes). Determinants of log-transformed adiponectin levels were evaluated by multiple linear regression analysis with interaction terms to determine whether predictors of adiponectin levels differed by diabetes status. Adiponectin levels were higher in type 1 diabetic than nondiabetic persons (13.5 (standard deviation: 1.0) vs. 8.8 (standard deviation: 1.0) microg/ml; p < 0.0001), adjusting for age, gender, body mass index, and glomerular filtration rate. The final regression model explained 67% of the difference in adiponectin levels between type 1 diabetic and nondiabetic persons. The variables explaining this difference included high density lipoprotein cholesterol, albumin excretion rate, plasminogen activator inhibitor-1, and hemoglobin A1c level. Adiponectin is higher in type 1 diabetic than nondiabetic persons. Although some of the difference can be explained, further study is needed to better understand the relation between elevated adiponectin levels and patient outcomes, including coronary heart disease. PMID:17591595

  14. The Activities of Lysyl Hydroxylase 3 (LH3) Regulate the Amount and Oligomerization Status of Adiponectin

    PubMed Central

    Ruotsalainen, Heli; Wang, Yu; Karppinen, Marjo; Bergmann, Ulrich; Kvist, Ari-Pekka; Pospiech, Helmut; Herzig, Karl-Heinz; Myllylä, Raili

    2012-01-01

    Lysyl hydroxylase 3 (LH3) has lysyl hydroxylase, galactosyltransferase, and glucosyltransferase activities, which are sequentially required for the formation of glucosylgalactosyl hydroxylysines in collagens. Here we demonstrate for the first time that LH3 also modifies the lysine residues in the collagenous domain of adiponectin, which has important roles in glucose and lipid metabolism and inflammation. Hydroxylation and, especially, glycosylation of the lysine residues of adiponectin have been shown to be essential for the formation of the more active high molecular weight adiponectin oligomers and thus for its function. In cells that totally lack LH3 enzyme, the galactosylhydroxylysine residues of adiponectin were not glucosylated to glucosylgalactosylhydroxylysine residues and the formation of high and middle molecular weight adiponectin oligomers was impaired. Circulating adiponectin levels in mutant mice lacking the lysyl hydroxylase activity of LH3 were significantly reduced, which indicates that LH3 is required for complete modification of lysine residues in adiponectin and the loss of some of the glycosylated hydroxylysine residues severely affects the secretion of adiponectin. LH mutant mice with reduced adiponectin level showed a high fat diet-induced increase in glucose, triglyceride, and LDL-cholesterol levels, hallmarks of the metabolic syndrome in humans. Our results reveal the first indication that LH3 is an important regulator of adiponectin biosynthesis, secretion and activity and thus might be a potential candidate for therapeutic applications in diseases associated with obesity and insulin resistance. PMID:23209641

  15. Adiponectin Reduces Hepatic Stellate Cell Migration by Promoting Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) Secretion*

    PubMed Central

    Ramezani-Moghadam, Mehdi; Wang, Jianhua; Ho, Vikki; Iseli, Tristan J.; Alzahrani, Badr; Xu, Aimin; Van der Poorten, David; Qiao, Liang; George, Jacob; Hebbard, Lionel

    2015-01-01

    Hepatic stellate cells (HSC) are central players in liver fibrosis that when activated, proliferate, migrate to sites of liver injury, and secrete extracellular matrix. Obesity, a known risk factor for liver fibrosis is associated with reduced levels of adiponectin, a protein that inhibits liver fibrosis in vivo and limits HSC proliferation and migration in vitro. Adiponectin-mediated activation of adenosine monophosphate-activated kinase (AMPK) inhibits HSC proliferation, but the mechanism by which it limits HSC migration to sites of injury is unknown. Here we sought to elucidate how adiponectin regulates HSC motility. Primary rat HSCs were isolated and treated with adiponectin in migration assays. The in vivo actions of adiponectin were examined by treating mice with carbon tetrachloride for 12 weeks and then injecting them with adiponectin. Cell and tissue samples were collected and analyzed for gene expression, signaling, and histology. Serum from patients with liver fibrosis was examined for adiponectin and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein. Adiponectin administration into mice increased TIMP-1 gene and protein expression. In cultured HSCs, adiponectin promoted TIMP-1 expression and through binding of TIMP-1 to the CD63/β1-integrin complex reduced phosphorylation of focal adhesion kinase to limit HSC migration. In mice with liver fibrosis, adiponectin had similar effects and limited focal adhesion kinase phosphorylation. Finally, in patients with advanced fibrosis, there was a positive correlation between serum adiponectin and TIMP-1 levels. In sum, these data show that adiponectin stimulates TIMP-1 secretion by HSCs to retard their migration and contributes to the anti-fibrotic effects of adiponectin. PMID:25575598

  16. Gender differences in adiponectin modulation of cardiac remodeling in mice deficient in endothelial nitric oxide synthase.

    PubMed

    Durand, Jorge L; Nawrocki, Andrea R; Scherer, Philipp E; Jelicks, Linda A

    2012-10-01

    Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease, a leading cause of death. Alterations in endothelial nitric oxide synthase (eNOS), an enzyme involved in regulating vascular tone, and in adiponectin, an adipocyte-derived secretory factor, are associated with cardiac remodeling. Deficiency of eNOS is associated with hypertension and LVH. Adiponectin exhibits vaso-protective, anti-inflammatory, and anti-atherogenic properties. We hypothesized that increased levels of adiponectin would alleviate cardiac pathology resulting from eNOS deficiency, while decreased levels of adiponectin would exacerbate the pathology. Male and female mice, deficient in eNOS, and either lacking or over-expressing adiponectin, were fed high fat diet (HFD) or normal chow. Cardiac magnetic resonance imaging was performed to serially assess heart morphology and function up to 40 weeks of age. Thirty-two weeks of HFD feeding led to significantly greater LV mass in male mice deficient in eNOS and either lacking or over-expressing adiponectin. Heart function was significantly reduced when the mice were deficient in either eNOS, adiponectin or both eNOS and adiponectin; for female mice, heart function was only reduced when both eNOS and adiponectin were lacking. Thus, while over-expression of adiponectin in the eNOS deficient HFD fed male mice preserved function at the expense of significantly increased LV mass, female mice were protected from decreased function and increased LVH by over-expression of adiponectin. Our results demonstrate a sexual dimorphism in response of the heart to alterations in eNOS and adiponectin during high fat feeding and suggest that adiponectin might require eNOS for some of its metabolic effects. PMID:22644792

  17. Genetics Home Reference: congenital leptin deficiency

    MedlinePlus

    ... is associated with severe early-onset obesity in humans. Nature. 1997 Jun 26;387(6636):903-8. Citation on PubMed O'Rahilly S. Leptin: defining its role in humans by the clinical study of genetic disorders. Nutr ...

  18. Regulation and Role of Leptin: Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent findings demonstrate that numerous genes i.e., relaxin, interleukins and other cytokines and biologically active substances such as leptin, insulin- like growth factor-I (IGF-I), and Agouti protein are produced by porcine adipose tissue, which could have a profound effect on appetite, immune...

  19. Serum adipokine concentrations in dogs with diabetes mellitus: a pilot study

    PubMed Central

    Kim, Ah Young; Kim, Hye-Sun; Yang, Mhan-Pyo

    2015-01-01

    This study was conducted to determine whether serum adipokine concentrations differed between healthy dogs and dogs with diabetes mellitus (DM). To accomplish this, 19 dogs with newly diagnosed DM were compared to 20 otherwise healthy dogs. The serum concentrations of visfatin, leptin, IL-1β, IL-6, IL-18, and TNF-α were significantly higher in diabetic dogs than in healthy dogs, whereas the serum adiponectin concentrations were lower in diabetic dogs. However, there were no significant differences in the IL-10 and resistin levels between groups. The serum leptin concentrations in diabetic dogs with and without concurrent disorders differed significantly. Treatment with insulin induced a significant decrease in IL-6 in diabetic dogs without concurrent disorders. These results show that the clinical diabetic state of dogs could modulate the circulating visfatin and adiponectin concentrations directly, while upregulation of leptin was probably a result of concurrent disorders rather than an effect of persistent hyperglycemia as a result of DM. PMID:25643799

  20. Adipocytokines in Systemic Lupus Erythematosus: Relationship to Inflammation, Insulin Resistance and Coronary Atherosclerosis

    PubMed Central

    Chung, Cecilia P.; Long, Ashley G.; Solus, Joseph F.; Rho, Young Hee; Oeser, Annette; Raggi, Paolo; Stein, C. Michael

    2009-01-01

    We tested the hypothesis that concentrations of adipocytokines are altered in SLE and associated with coronary atherosclerosis, insulin resistance and inflammation. Concentrations of resistin, leptin, adiponectin, and visfatin were measured in 109 patients with SLE and in 78 control subjects. Coronary calcification was measured by electron beam computed tomography and insulin resistance was defined by the homeostasis (HOMA) index. Concentrations of adiponectin (28.7+/−17.9 vs. 22.0+/−15.3 µg/mL, p=0.003), leptin (41.1+/−49.9 vs. 19.8+/−24.6 ng/mL, p<0.001) and visfatin (7.5+/−10.5 vs. 4.5+/−2.8 ng/mL, p<0.001) were higher in patients with SLE than controls. These differences remained significant after adjustment for age, race, sex and BMI, (all p-values<0.02). Concentrations of resistin (10.7+/−7.6 vs. 9.1+/−5.1 ng/mL, p=0.41) did not differ in patients and controls. In patients with SLE, leptin was positively associated with BMI (rho=0.80, p<0.001), insulin resistance (rho=0.46, p<0.001), and CRP (rho=0.30, p=0.002), while adiponectin was negatively associated with the same factors (rho= −0.40, p<0.001; rho= −0.38, p<0.001, rho=− 0.22, p=0.02, respectively). None of the adipocytokines were associated with coronary atherosclerosis in SLE. In conclusion, patients with SLE have increased concentrations of adiponectin, leptin and visfatin. Lower concentrations of adiponectin and higher concentrations of leptin are associated with insulin resistance, BMI and CRP in patients with SLE. PMID:19578104

  1. Circulating soluble leptin receptor and free leptin index during childhood, puberty, and adolescence.

    PubMed

    Kratzsch, J; Lammert, A; Bottner, A; Seidel, B; Mueller, G; Thiery, J; Hebebrand, J; Kiess, W

    2002-10-01

    Leptin is bound in human blood by a high affinity binding protein, which appears to be identical with the soluble leptin receptor (sOB-R). Using a ligand-mediated immunofunctional assay for the determination of serum sOB-R, we investigated its course during childhood, puberty, and adolescence in a large cohort of 581 healthy children and adolescents and a small group of 13 patients with anorexia nervosa. In the first years of life, sOB-R is detectable in remarkably high concentrations. Thereafter, a continuous decline of sOB-R levels was found. Consequently, correlation analyses demonstrated significant inverse relationships (P < 0.001) of sOB-R with age, IGF-I levels, pubertal stage, auxological and body composition parameters, as well as with leptin concentrations. Multiple regression analysis revealed that height, IGF-I, and age (only in girls) were independent predictors of sOB-R levels; these variables account for approximately 65% and 48% of the variation of sOB-R levels in boys and girls, respectively. The courses of age-dependent median values for the free leptin index (FLI, ratio between leptin and sOB-R levels) and for leptin levels were parallel in both genders. Correlation analyses demonstrated that in particular parameters of growth and sexual maturation are more closely related to the FLI than to leptin alone; this closer relationship is more pronounced among boys. Weight gains of patients with anorexia nervosa resulted in a significant increase in leptin and IGF-I levels (P < 0.01), whereas the median of sOB-R values decreased (P < 0.01). sOB-R and IGF-I levels were again significantly correlated (r = -0.55, P < 0.01). These findings suggest that high levels of sOB-R in emaciation may reflect an up-regulation of the sOB-R to suppress leptin action during energy deficiency. Furthermore, determinations of sOB-R and FLI are additional valuable tools to investigate the leptin axis during growth and sexual maturation. PMID:12364439

  2. Leptin Suppresses Mouse Taste Cell Responses to Sweet Compounds.

    PubMed

    Yoshida, Ryusuke; Noguchi, Kenshi; Shigemura, Noriatsu; Jyotaki, Masafumi; Takahashi, Ichiro; Margolskee, Robert F; Ninomiya, Yuzo

    2015-11-01

    Leptin is known to selectively suppress neural and behavioral responses to sweet-tasting compounds. However, the molecular basis for the effect of leptin on sweet taste is not known. Here, we report that leptin suppresses sweet taste via leptin receptors (Ob-Rb) and KATP channels expressed selectively in sweet-sensitive taste cells. Ob-Rb was more often expressed in taste cells that expressed T1R3 (a sweet receptor component) than in those that expressed glutamate-aspartate transporter (a marker for Type I taste cells) or GAD67 (a marker for Type III taste cells). Systemically administered leptin suppressed taste cell responses to sweet but not to bitter or sour compounds. This effect was blocked by a leptin antagonist and was absent in leptin receptor-deficient db/db mice and mice with diet-induced obesity. Blocking the KATP channel subunit sulfonylurea receptor 1, which was frequently coexpressed with Ob-Rb in T1R3-expressing taste cells, eliminated the effect of leptin on sweet taste. In contrast, activating the KATP channel with diazoxide mimicked the sweet-suppressing effect of leptin. These results indicate that leptin acts via Ob-Rb and KATP channels that are present in T1R3-expressing taste cells to selectively suppress their responses to sweet compounds. PMID:26116698

  3. Control of respiratory and cardiovascular functions by leptin

    PubMed Central

    Bassi, M.; Werner, I.F.; Zoccal, D.B.; Menani, J.V.; Colombari, E.; Hall, J.E.; da Silva, A.A.; do Carmo, J.M.; Colombari, D.S.A.

    2015-01-01

    Leptin, a peptide hormone produced by adipose tissue, acts in brain centers that control critical physiological functions such as metabolism, breathing and cardiovascular regulation. The importance of leptin for respiratory control is evident by the fact that leptin deficient mice exhibit impaired ventilatory responses to carbon dioxide (CO2), which can be corrected by intracerebroventricular leptin replacement therapy. Leptin is also recognized as an important link between obesity and hypertension. Humans and animal models lacking either leptin or functional leptin receptors exhibit many characteristics of the metabolic syndrome, including hyperinsulinemia, insulin resistance, hyperglycemia, dyslipidemia and visceral adiposity, but do not exhibit increased sympathetic nerve activity (SNA) and have normal to lower blood pressure (BP) compared to lean controls. Even though previous studies have extensively focused on the brain sites and intracellular signaling pathways involved in leptin effects on food intake and energy balance, the mechanisms that mediate the actions of leptin on breathing and cardiovascular function are only beginning to be elucidated. This mini-review summarizes recent advances on the effects of leptin on cardiovascular and respiratory control with emphasis on the neural control of respiratory function and autonomic activity. PMID:25645056

  4. Leptin's effect on taste bud calcium responses and transmitter secretion.

    PubMed

    Meredith, Tricia L; Corcoran, Alan; Roper, Stephen D

    2015-05-01

    Leptin, a peptide hormone released by adipose tissue, acts on the hypothalamus to control cravings and appetite. Leptin also acts to decrease taste responses to sweet substances, though there is little detailed information regarding where leptin acts in the taste transduction cascade. The present study examined the effects of leptin on sweet-evoked responses and neuro transmitter release from isolated taste buds. Our results indicate that leptin moderately decreased sweet-evoked calcium mobilization in isolated mouse taste buds. We also employed Chinese hamster ovary biosensor cells to examine taste transmitter release from isolated taste buds. Leptin reduced ATP and increased serotonin release in response to sweet stimulation. However, leptin has no effect on bitter-evoked transmitter release, further showing that the action of leptin is sweet specific. Our results support those of previous studies, which state that leptin acts on taste tissue via the leptin receptor, most likely on Type II (Receptor) cells, but also possibly on Type III (Presynaptic) cells. PMID:25537017

  5. Lean heart: Role of leptin in cardiac hypertrophy and metabolism.

    PubMed

    Hall, Michael E; Harmancey, Romain; Stec, David E

    2015-09-26

    Leptin is an adipokine that has been linked with the cardiovascular complications resulting from obesity such as hypertension and heart disease. Obese patients have high levels of circulating leptin due to increased fat mass. Clinical and population studies have correlated high levels of circulating leptin with the development of cardiac hypertrophy in obesity. Leptin has also been demonstrated to increase the growth of cultured cardiomyocytes. However, several animal studies of obese leptin deficient mice have not supported a role for leptin in promoting cardiac hypertrophy so the role of leptin in this pathological process remains unclear. Leptin is also an important hormone in the regulation of cardiac metabolism where it supports oxidation of glucose and fatty acids. In addition, leptin plays a critical role in protecting the heart from excess lipid accumulation and the formation of toxic lipids in obesity a condition known as cardiac lipotoxicity. This paper focuses on the data supporting and refuting leptin's role in promoting cardiac hypertrophy as well as its important role in the regulation of cardiac metabolism and protection against cardiac lipotoxicity. PMID:26413228

  6. Association of Leptin with Body Pain in Women.

    PubMed

    Younger, Jarred; Kapphahn, Kristopher; Brennan, Kathleen; Sullivan, Shannon D; Stefanick, Marcia L

    2016-07-01

    Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory adipokine. One of the effects of increased systemic leptin concentrations may be greater sensitivity to pain. We report the results of two studies examining the association between leptin and pain: a small pilot longitudinal study, followed by a large cross-sectional study. In Study 1, three women with physician-diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as well as daily self-reported musculoskeletal pain. Daily fluctuations in serum leptin were positively associated with pain across all three participants (F (1,63) = 12.8, p < 0.001), with leptin predicting ∼49% of the pain variance. In Study 2, the relationship between leptin and body pain was examined in a retrospective cross-sectional analysis of 5676 generally healthy postmenopausal women from the Women's Health Initiative. Leptin levels obtained from single blood draws were tested for a relationship with self-reported body pain. Body mass index (BMI) was also included as a predictor of pain. Both leptin and BMI were found to be independently associated with self-reported pain (p = 0.001 and p < 0.001, respectively), with higher leptin levels and greater BMI each being associated with greater pain. Leptin appears to be a predictor of body pain both within- and between-individuals and may be a driver of generalized pain states such as fibromyalgia. PMID:27028709

  7. Understanding leptin-dependent regulation of skeletal homeostasis

    PubMed Central

    Motyl, Katherine J.; Rosen, Clifford J.

    2012-01-01

    Despite growing evidence for adipose tissue regulation of bone mass, the role of the adipokine leptin in bone remodeling remains controversial. The majority of in vitro studies suggest leptin enhances osteoblastic proliferation and differentiation while inhibiting adipogenic differentiation from marrow stromal cells. Alternatively, some evidence demonstrates either no effect or a pro-apoptotic action of leptin on stromal cells. Similarly, in vivo work has demonstrated both positive and negative effects of leptin on bone mass. Most of the literature supports the idea that leptin suppresses bone mass by acting in the brainstem to reduce serotonin-dependent sympathetic signaling from the ventromedial hypothalamus to bone. However, other studies have found partly or entirely contrasting actions of leptin. Recently one study found a significant effect of surgery alone with intracerebroventricular administration of leptin, a technique crucial for understanding centrally-mediated leptin regulation of bone. Thus, two mainstream hypotheses for the role of leptin on bone emerge: 1) direct regulation through increased osteoblast proliferation and differentiation and 2) indirect suppression of bone formation through a hypothalamic relay. At the present time, it remains unclear whether these effects are relevant in only extreme circumstances (i.e. models with complete deficiency) or play an important homeostatic role in the regulation of peak bone acquisition and skeletal remodeling. Ultimately, determining the actions of leptin on the skeleton will be critical for understanding how the obesity epidemic may be impacting the prevalence of osteoporosis. PMID:22534195

  8. Association of Leptin with Body Pain in Women

    PubMed Central

    Kapphahn, Kristopher; Brennan, Kathleen; Sullivan, Shannon D.; Stefanick, Marcia L.

    2016-01-01

    Abstract Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory adipokine. One of the effects of increased systemic leptin concentrations may be greater sensitivity to pain. We report the results of two studies examining the association between leptin and pain: a small pilot longitudinal study, followed by a large cross-sectional study. In Study 1, three women with physician-diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as well as daily self-reported musculoskeletal pain. Daily fluctuations in serum leptin were positively associated with pain across all three participants (F (1,63) = 12.8, p < 0.001), with leptin predicting ∼49% of the pain variance. In Study 2, the relationship between leptin and body pain was examined in a retrospective cross-sectional analysis of 5676 generally healthy postmenopausal women from the Women's Health Initiative. Leptin levels obtained from single blood draws were tested for a relationship with self-reported body pain. Body mass index (BMI) was also included as a predictor of pain. Both leptin and BMI were found to be independently associated with self-reported pain (p = 0.001 and p < 0.001, respectively), with higher leptin levels and greater BMI each being associated with greater pain. Leptin appears to be a predictor of body pain both within- and between-individuals and may be a driver of generalized pain states such as fibromyalgia. PMID:27028709

  9. Leptin Promotes Wound Healing in the Oral Mucosa

    PubMed Central

    Umeki, Hirochika; Tokuyama, Reiko; Ide, Shinji; Okubo, Mitsuru; Tadokoro, Susumu; Tezuka, Mitsuki; Tatehara, Seiko; Satomura, Kazuhito

    2014-01-01

    Introduction Leptin, a 16 kDa circulating anti-obesity hormone, exhibits many physiological properties. Recently, leptin was isolated from saliva; however, its function in the oral cavity is still unclear. In this study, we investigated the physiological role of leptin in the oral cavity by focusing on its effect on wound healing in the oral mucosa. Methods Immunohistochemical analysis was used to examine the expression of the leptin receptor (Ob-R) in human/rabbit oral mucosa. To investigate the effect of leptin on wound healing in the oral mucosa, chemical wounds were created in rabbit oral mucosa, and leptin was topically administered to the wound. The process of wound repair was histologically observed and quantitatively analyzed by measuring the area of ulceration and the duration required for complete healing. The effect of leptin on the proliferation, differentiation and migration of human oral mucosal epithelial cells (RT7 cells) was investigated using crystal violet staining, reverse transcription polymerase chain reaction (RT-PCR) and a wound healing assay, respectively. Results Ob-R was expressed in spinous/granular cells in the epithelial tissue and vascular endothelial cells in the subepithelial connective tissue of the oral mucosa. Topical administration of leptin significantly promoted wound healing and shortened the duration required for complete healing. Histological analysis of gingival tissue beneath the ulceration showed a denser distribution of blood vessels in the leptin-treated group. Although the proliferation and differentiation of RT7 cells were not affected by leptin, the migration of these cells was accelerated in the presence of leptin. Conclusion Topically administered leptin was shown to promote wound healing in the oral mucosa by accelerating epithelial cell migration and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound

  10. Leptin as a modulator of neuroendocrine function in humans.

    PubMed

    Khan, Sami M; Hamnvik, Ole-Petter R; Brinkoetter, Mary; Mantzoros, Christos S

    2012-07-01

    Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of energy stored in fat, plays a central role in regulating human energy homeostasis. In addition, leptin plays a significant permissive role in the physiological regulation of several neuroendocrine axes, including the hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes. Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a state of energy deprivation. Hypoleptinemia can be a congenital or acquired condition, and is associated with alterations of the aforementioned axes aimed at promoting survival. More specifically, gonadotropin levels decrease and become less pulsatile under conditions of energy deprivation, and these changes can be at least partially reversed through leptin administration in physiological replacement doses. Similarly, leptin deficiency is associated with thyroid axis abnormalities including abnormal levels of thyrotropin-releasing hormone, and leptin administration may at least partially attenuate this effect. Leptin deficiency results in decreased insulin-like growth factor 1 levels which can be partially ameliorated through leptin administration, and leptin appears to have a much more pronounced effect on the growth of rodents than that of humans. Similarly, adrenal axis function is regulated more tightly by low leptin in rodents than in humans. In addition to congenital leptin deficiency, conditions that may be associated with decreased leptin levels include hypothalamic amenorrhea, anorexia nervosa, and congenital or acquired lipodystrophy syndromes. Accumulating evidence from proof of concept studies suggests that leptin administration, in replacement doses, may ameliorate neuroendocrine abnormalities in individuals who suffer from these conditions. PMID:22665330

  11. Leptin promotes cell proliferation and survival of trophoblastic cells.

    PubMed

    Magariños, María Paula; Sánchez-Margalet, Víctor; Kotler, Mónica; Calvo, Juan Carlos; Varone, Cecilia L

    2007-02-01

    Leptin, the 16-kDa protein product of the obese gene, was originally considered as an adipocyte-derived signaling molecule for the central control of metabolism. However, leptin has been suggested to be involved in other functions during pregnancy, particularly in placenta. In the present work, we studied a possible effect of leptin on trophoblastic cell proliferation, survival, and apoptosis. Recombinant human leptin added to JEG-3 and BeWo choriocarcinoma cell lines showed a stimulatory effect on cell proliferation up to 3 and 2.4 times, respectively, measured by (3)H-thymidine incorporation and cell counting. These effects were time and dose dependent. Maximal effect was achieved at 250 ng leptin/ml for JEG-3 cells and 50 ng leptin/ml for BeWo cells. Moreover, by inhibiting endogenous leptin expression with 2 microM of an antisense oligonucleotide (AS), cell proliferation was diminished. We analyzed cell population distribution during the different stages of cell cycle by fluorescence-activated cell sorting, and we found that leptin treatment displaced the cells towards a G2/M phase. We also found that leptin upregulated cyclin D1 expression, one of the key cell cycle-signaling proteins. Since proliferation and death processes are intimately related, the effect of leptin on cell apoptosis was investigated. Treatment with 2 microM leptin AS increased the number of apoptotic cells 60 times, as assessed by annexin V-fluorescein isothiocyanate/propidium iodide staining, and the caspase-3 activity was increased more than 2 fold. This effect was prevented by the addition of 100 ng leptin/ml. In conclusion, we provide evidence that suggests that leptin is a trophic and mitogenic factor for trophoblastic cells by virtue of its inhibiting apoptosis and promoting proliferation. PMID:17021346

  12. Leptin as a Modulator of Neuroendocrine Function in Humans

    PubMed Central

    Khan, Sami M.; Hamnvik, Ole-Petter R.; Brinkoetter, Mary

    2012-01-01

    Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of energy stored in fat, plays a central role in regulating human energy homeostasis. In addition, leptin plays a significant permissive role in the physiological regulation of several neuroendocrine axes, including the hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes. Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a state of energy deprivation. Hypoleptinemia can be a congenital or acquired condition, and is associated with alterations of the aforementioned axes aimed at promoting survival. More specifically, gonadotropin levels decrease and become less pulsatile under conditions of energy deprivation, and these changes can be at least partially reversed through leptin administration in physiological replacement doses. Similarly, leptin deficiency is associated with thyroid axis abnormalities including abnormal levels of thyrotropin-releasing hormone, and leptin administration may at least partially attenuate this effect. Leptin deficiency results in decreased insulin-like growth factor 1 levels which can be partially ameliorated through leptin administration, and leptin appears to have a much more pronounced effect on the growth of rodents than that of humans. Similarly, adrenal axis function is regulated more tightly by low leptin in rodents than in humans. In addition to congenital leptin deficiency, conditions that may be associated with decreased leptin levels include hypothalamic amenorrhea, anorexia nervosa, and congenital or acquired lipodystrophy syndromes. Accumulating evidence from proof of concept studies suggests that leptin administration, in replacement doses, may ameliorate neuroendocrine abnormalities in individuals who suffer from these conditions. PMID:22665330

  13. Adipokines and Insulin Resistance in Young Adult Survivors of Childhood Cancer

    PubMed Central

    Latoch, Eryk; Muszynska-Roslan, Katarzyna; Panas, Agata; Panasiuk, Anna; Sawicka-Zukowska, Malgorzata; Zelazowska-Rutkowska, Beata; Zabrocka, Ewa; Krawczuk-Rybak, Maryna

    2016-01-01

    We examined the association between adipokines (leptin, adiponectin, and resistin), radiotherapy, measurement of body fat, and insulin resistance among young adult survivors of childhood cancer (CCS). Materials and Methods. Seventy-six survivors were included (mean age 24.1 ± 3.5 years). Insulin resistance (IR) was calculated using the homeostasis model assessment (HOMA-IR). The serum levels of adipokines were assayed by immunoassays. Fat mass was evaluated by DXA. Results. Mean adiponectin level and mean body FAT were higher in the examined females than in males (10009 ± 6367 ng/mL versus 6433 ± 4136 ng/mL, p < 0.01; 35.98 ± 9.61% versus 22.7 ± 7.46%, p < 0.001). Among CCS, one of 75 patients met the criteria of insulin resistance, and in 14 patients there was impaired fasting glucose. The multiple regression model for females showed that leptin/adiponectin ratio (LA ratio) significantly affected HOMA-IR (increase of 0.024 per each unit of LA ratio; p < 0.05). Radiotherapy had no effect on serum adipokines and IR. Conclusion. The observed results support the hypothesis that adiponectin might be associated with insulin resistance and it can not be ruled out that changes in the mean level of adiponectin per FAT mass or leptin/adiponectin ratio may precede the occurrence of insulin resistance in the future. PMID:27212946

  14. Disulfide-dependent self-assembly of adiponectin octadecamers from trimers and presence of stable octadecameric adiponectin lacking disulfide bonds in vitro.

    PubMed

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

    2009-12-29

    Adiponectin is a circulating insulin-sensitizing hormone that homooligomerizes 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 reassembly 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 nanoelectrospray 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

  15. Kinetics of Leptin Binding to the Q223R Leptin Receptor

    PubMed Central

    Verkerke, Hans; Naylor, Caitlin; Zabeau, Lennart; Tavernier, Jan; Petri, William A.; Marie, Chelsea

    2014-01-01

    Studies in human populations and mouse models of disease have linked the common leptin receptor Q223R mutation to obesity, multiple forms of cancer, adverse drug reactions, and susceptibility to enteric and respiratory infections. Contradictory results cast doubt on the phenotypic consequences of this variant. We set out to determine whether the Q223R substitution affects leptin binding kinetics using surface plasmon resonance (SPR), a technique that allows sensitive real-time monitoring of protein-protein interactions. We measured the binding and dissociation rate constants for leptin to the extracellular domain of WT and Q223R murine leptin receptors expressed as Fc-fusion proteins and found that the mutant receptor does not significantly differ in kinetics of leptin binding from the WT leptin receptor. (WT: ka 1.76×106±0.193×106 M−1 s−1, kd 1.21×10−4±0.707×10−4 s−1, KD 6.47×10−11±3.30×10−11 M; Q223R: ka 1.75×106±0.0245×106 M−1 s−1, kd 1.47×10−4±0.0505×10−4 s−1, KD 8.43×10−11±0.407×10−11 M). Our results support earlier findings that differences in affinity and kinetics of leptin binding are unlikely to explain mechanistically the phenotypes that have been linked to this common genetic variant. Future studies will seek to elucidate the mechanism by which this mutation influences susceptibility to metabolic, infectious, and malignant pathologies. PMID:24743494

  16. Chronic Oxytocin Administration as a Treatment Against Impaired Leptin Signaling or Leptin Resistance in Obesity

    PubMed Central

    Altirriba, Jordi; Poher, Anne-Laure; Rohner-Jeanrenaud, Françoise

    2015-01-01

    This review summarizes the existing literature on the effects of oxytocin administration in the treatment of obesity in different animal models and in humans, focusing on the central control of food intake, the oxytocin effects on adipose tissue, and the relationships between oxytocin and leptin. Oxytocin is a hypothalamic nonapeptide synthesized mainly in the paraventricular and supraoptic nuclei projecting to the pituitary, where it reaches the peripheral circulation, as well as to other brain regions. Moreover, leptin modulates oxytocin levels and activates oxytocin neurons in the hypothalamic paraventricular nucleus, which innervates the nucleus of the solitary tract, partly responsible for the brain-elicited oxytocin effects. Taking into account that oxytocin is located downstream leptin, it was hypothesized that oxytocin treatment would be effective in decreasing body weight in leptin-resistant DIO animals, as well as in those with leptin or with leptin receptor deficiency. Several groups have demonstrated that in such animal models (rats, mice, and rhesus monkeys), central or peripheral oxytocin administration decreases body weight, mainly due to a decrease in fat mass, demonstrating that an oxytocin treatment is able to partly overcome leptin deficiency or resistance. Moreover, a pilot clinical study demonstrated the efficiency of oxytocin in the treatment of obesity in human subjects, confirming the results obtained in the different animal models. Larger multicenter studies are now needed to determine whether the beneficial effects of oxytocin treatment can apply not only to obese but also to type 2 diabetic patients. These studies should also shed some light on the molecular mechanisms of oxytocin action in humans. PMID:26300847

  17. Contribution of leptin receptor N-linked glycans to leptin binding.

    PubMed

    Kamikubo, Yuichi; Dellas, Claudia; Loskutoff, David J; Quigley, James P; Ruggeri, Zaverio M

    2008-03-15

    The extracellular domain of the human leptin receptor (Ob-R) contains 20 potential N-glycosylation sites whose role in leptin binding remains to be elucidated. We found that a mammalian cell-expressed sOb-R (soluble Ob-R) fragment (residues 22-839 of the extracellular domain) bound leptin with a dissociation constant of 1.8 nM. This binding was inhibited by Con A (concanavalin A) or wheatgerm agglutinin. Treatment of sOb-R with peptide N-glycosidase F reduced leptin binding by approximately 80% concurrently with N-linked glycan removal. The human megakaryoblastic cell line, MEG-01, expresses two forms of the Ob-R, of approx. 170 and 130 kDa molecular mass. Endo H (endoglycosidase H) treatment and cell culture with alpha-glucosidase inhibitors demonstrated that N-linked glycans are of the complex mature type in the 170 kDa form and of the high-mannose type in the 130 kDa form. Both isoforms bound leptin, but not after peptide N-glycosidase F treatment. An insect-cell-expressed sOb-R fragment, consisting of the Ig (immunoglobulin), CRH2 (second cytokine receptor homology) and FNIII (fibronectin type III) domains, bound leptin with affinity similar to that of the entire extracellular domain, but this function was abolished after N-linked glycan removal. The same treatment had no effect on the leptin-binding activity of the isolated CRH2 domain. Our findings show that N-linked glycans within Ig and/or FNIII domains regulate Ob-R function, but are not involved in essential interactions with the ligand. PMID:17983356

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

    PubMed

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

    2016-01-01

    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

  19. 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

  20. Leptin Increases Striatal Dopamine D2 Receptor Binding in Leptin-Deficient Obese (ob/ob) Mice

    SciTech Connect

    Pfaffly, J.; Michaelides, M.; Wang, G-J.; Pessin, J.E.; Volkow, N.D.; Thanos, P.K.

    2010-06-01

    Peripheral and central leptin administration have been shown to mediate central dopamine (DA) signaling. Leptin-receptor deficient rodents show decreased DA D2 receptor (D2R) binding in striatum and unique DA profiles compared to controls. Leptin-deficient mice show increased DA activity in reward-related brain regions. The objective of this study was to examine whether basal D2R-binding differences contribute to the phenotypic behaviors of leptin-deficient ob/ob mice, and whether D2R binding is altered in response to peripheral leptin treatment in these mice. Leptin decreased body weight, food intake, and plasma insulin concentration in ob/ob mice but not in wild-type mice. Basal striatal D2R binding (measured with autoradiography [{sup 3}H] spiperone) did not differ between ob/ob and wild-type mice but the response to leptin did. In wild-type mice, leptin decreased striatal D2R binding, whereas, in ob/ob mice, leptin increased D2R binding. Our findings provide further evidence that leptin modulates D2R expression in striatum and that these effects are genotype/phenotype dependent.

  1. Leptin inhibits testosterone secretion from adult rat testis in vitro.

    PubMed

    Tena-Sempere, M; Pinilla, L; González, L C; Diéguez, C; Casanueva, F F; Aguilar, E

    1999-05-01

    Leptin, the product of the ob gene, has emerged recently as a pivotal signal in the regulation of fertility. Although the actions of leptin in the control of reproductive function are thought to be exerted mainly at the hypothalamic level, the potential direct effects of leptin at the pituitary and gonadal level have been poorly characterised. In the present study, we first assessed the ability of leptin to regulate testicular testosterone secretion in vitro. Secondly, we aimed to evaluate whether leptin can modulate basal gonadotrophin and prolactin (PRL) release by incubated hemi-pituitaries from fasted male rats. To attain the first goal, testicular slices from prepubertal and adult rats were incubated with increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Assuming that in vitro testicular responsiveness to leptin may be dependent on the background leptin levels, testicular tissue from both food-deprived and normally-fed animals was used. Furthermore, leptin modulation of stimulated testosterone secretion was evaluated by incubation of testicular samples with different doses of leptin in the presence of 10 IU human chorionic gonadotrophin (hCG). In addition, analysis of leptin actions on pituitary function was carried out using hemi-pituitaries from fasted adult male rats incubated in the presence of increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Serum testosterone levels, and basal and hCG-stimulated testosterone secretion by incubated testicular tissue were significantly decreased by fasting in prepubertal and adult male rats. However, a significant reduction in circulating LH levels was only evident in adult fasted rats. Doses of 10(-9)-10(-7) M leptin had no effect on basal or hCG-stimulated testosterone secretion by testes from prepubertal rats, regardless of the nutritional state of the donor animal. In contrast, leptin significantly decreased basal and hCG-induced testosterone secretion by testes from fasted and fed

  2. The Rab11 Effector Protein FIP1 Regulates Adiponectin Trafficking and Secretion

    PubMed Central

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

    2013-01-01

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

  3. 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. PMID:19299452

  4. Pharmacological ceramide reduction alleviates alcohol-induced steatosis and hepatomegaly in adiponectin knockout mice

    PubMed Central

    Correnti, Jason M.; Juskeviciute, Egle; Swarup, Aditi

    2014-01-01

    Hepatosteatosis, the ectopic accumulation of lipid in the liver, is one of the earliest clinical signs of alcoholic liver disease (ALD). Alcohol-dependent deregulation of liver ceramide levels as well as inhibition of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPAR-α) activity are thought to contribute to hepatosteatosis development. Adiponectin can regulate lipid handling in the liver and has been shown to reduce ceramide levels and activate AMPK and PPAR-α. However, the mechanisms by which adiponectin prevents alcoholic hepatosteatosis remain incompletely characterized. To address this question, we assessed ALD progression in wild-type (WT) and adiponectin knockout (KO) mice fed an ethanol-containing liquid diet or isocaloric control diet. Adiponectin KO mice relative to WT had increased alcohol-induced hepatosteatosis and hepatomegaly, similar modest increases in serum alanine aminotransferase, and reduced liver TNF. Restoring circulating adiponectin levels using recombinant adiponectin ameliorated alcohol-induced hepatosteatosis and hepatomegaly in adiponectin KO mice. Alcohol-fed WT and adiponectin KO animals had equivalent reductions in AMPK protein and PPAR-α DNA binding activity compared with control-fed animals. No difference in P-AMPK/AMPK ratio was detected, suggesting that alcohol-dependent deregulation of AMPK and PPAR-α in the absence of adiponectin are not primary causes of the observed increase in hepatosteatosis in these animals. By contrast, alcohol treatment increased liver ceramide levels in adiponectin KO but not WT mice. Importantly, pharmacological inhibition of de novo ceramide synthesis in adiponectin KO mice abrogated alcohol-mediated increases in liver ceramides, steatosis, and hepatomegaly. These data suggest that adiponectin reduces alcohol-induced steatosis and hepatomegaly through regulation of liver ceramides, but its absence does not exacerbate alcohol-induced liver damage. PMID

  5. Placental restriction of fetal growth decreases IGF1 and leptin mRNA expression in the perirenal adipose tissue of late gestation fetal sheep.

    PubMed

    Duffield, Jaime A; Vuocolo, Tony; Tellam, Ross; Yuen, Bernard S; Muhlhausler, Beverly S; McMillen, I Caroline

    2008-05-01

    Placental restriction (PR) of fetal growth results in a low birth weight and an increased visceral fat mass in postnatal life. We investigated whether PR alters expression of genes that regulate adipogenesis [IGF1, IGF1 receptor (IGF1R), IGF2, IGF2R, proliferator-activated receptor-gamma, retinoid-X-receptor-alpha], adipocyte metabolism (lipoprotein lipase, G3PDH, GAPDH) and adipokine signaling (leptin, adiponectin) in visceral adipose tissue before birth. PR was induced by removal of the majority of endometrial caruncles in nonpregnant ewes before mating. Fetal blood samples were collected from 116 days gestation, and perirenal visceral adipose tissue (PAT) was collected from PR and control fetuses at 145 days. PAT gene expression was measured by quantitative RT-PCR. PR fetuses had a lower weight (PR 2.90 +/- 0.32 kg; control, 5.12 +/- 0.24 kg; P < 0.0001), mean gestational arterial Po(2) (P < 0.0001), plasma glucose (P < 0.01), and insulin concentrations (P < 0.02), than controls. The expression of IGF1 mRNA in PAT was lower in the PR fetuses (PR, 0.332 +/- 0.063; control, 0.741 +/- 0.083; P < 0.01). Leptin mRNA expression in PAT was also lower in PR fetuses (PR, 0.077 +/- 0.009; control, 0.115 +/- 0.013; P < 0.05), although there was no difference in the expression of other adipokine or adipogenic genes in PAT between PR and control fetuses. Thus, restriction of placental and hence, fetal substrate supply results in decreased IGF1 and leptin expression in fetal visceral adipose tissue, which may alter the functional development of the perirenal fat depot and contribute to altered leptin signaling in the growth-restricted newborn and the subsequent emergence of an increased visceral adiposity. PMID:18272661

  6. Biologically inactive leptin and early-onset extreme obesity.

    PubMed

    Wabitsch, Martin; Funcke, Jan-Bernd; Lennerz, Belinda; Kuhnle-Krahl, Ursula; Lahr, Georgia; Debatin, Klaus-Michael; Vatter, Petra; Gierschik, Peter; Moepps, Barbara; Fischer-Posovszky, Pamela

    2015-01-01

    Mutations in the gene encoding leptin (LEP) typically lead to an absence of circulating leptin and to extreme obesity. We describe a 2-year-old boy with early-onset extreme obesity due to a novel homozygous transversion (c.298G→T) in LEP, leading to a change from aspartic acid to tyrosine at amino acid position 100 (p.D100Y) and high immunoreactive levels of leptin. Overexpression studies confirmed that the mutant protein is secreted but neither binds to nor activates the leptin receptor. The mutant protein failed to reduce food intake and body weight in leptin-deficient ob/ob mice. Treatment of the patient with recombinant human leptin (metreleptin) rapidly normalized eating behavior and resulted in weight loss. PMID:25551525

  7. Effect of Obesity and Leptin Level on Migraineurs

    PubMed Central

    Ligong, Zhang; Jinjin, Qin; Chunfu, Chen; Congcong, Li; Xiaojun, Diao

    2015-01-01

    Background The aim of this study was to analyze the effects of obesity and leptin levels on patients with migraine, and to observe the change of leptin levels in migraineurs. Material/Methods We enrolled 52 migraine patients from the Headache Clinic in Shandong Provincial Hospital into a randomized controlled trial with another 52 age-, sex-, and BMI-matched healthy subjects as controls. Leptin levels in all subjects were determined by radioimmunoassay. Results Compared with the control group, the migraineurs revealed no significant change in leptin levels (P>0.05). Multivariate Logistic regression analysis showed that neither abdominal obesity nor leptin had significant impact on migraine clinical features. Total body obesity had a significant effect on the frequency (OR=4.248), duration (OR=3.167), and intensity (OR=5.225) of the headache. Conclusions Total body obesity affected headache frequency, intensity, and duration, while leptin levels did not. PMID:26508370

  8. Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay.

    PubMed

    Sun, Yiyi; Zang, Zhihe; Zhong, Ling; Wu, Min; Su, Qing; Gao, Xiurong; Zan, Wang; Lin, Dong; Zhao, Yan; Zhang, Zhonglin

    2013-01-01

    Adiponectin, the adipose-derived hormone, plays an important role in the suppression of metabolic disorders that can result in type 2 diabetes, obesity, and atherosclerosis. It has been shown that up-regulation of adiponectin or adiponectin receptor has a number of therapeutic benefits. Given that it is hard to convert the full size adiponectin protein into a viable drug, adiponectin receptor agonists could be designed or identified using high-throughput screening. Here, we report on the development of a two-step screening process to identify adiponectin agonists. First step, we developed a high throughput screening assay based on fluorescence polarization to identify adiponectin ligands. The fluorescence polarization assay reported here could be adapted to screening against larger small molecular compound libraries. A natural product library containing 10,000 compounds was screened and 9 hits were selected for validation. These compounds have been taken for the second-step in vitro tests to confirm their agonistic activity. The most active adiponectin receptor 1 agonists are matairesinol, arctiin, (-)-arctigenin and gramine. The most active adiponectin receptor 2 agonists are parthenolide, taxifoliol, deoxyschizandrin, and syringin. These compounds may be useful drug candidates for hypoadiponectin related diseases. PMID:23691032

  9. Adiponectin resides in mouse skin and upregulates hyaluronan synthesis in dermal fibroblasts.

    PubMed

    Akazawa, Yumiko; Sayo, Tetsuya; Sugiyama, Yoshinori; Sato, Takashi; Akimoto, Noriko; Ito, Akira; Inoue, Shintaro

    2011-01-01

    Adipose tissue is a hormonally active tissue that produces adipokines that influence the activity of other tissues. Adiponectin is an adipocyte-specific adipokine involved in systemic metabolism. We detected the expression of adiponectin receptors (AdipoR1 and AdipoR2) mRNA in cultured dermal fibroblasts. The full-length adiponectin (fAd), but not the globular adiponectin (gAd), increased hyaluronan (HA) production and upregulated HA synthase (HAS) 2 mRNA expression. AdipoR1 and AdipoR2 mRNAs were also expressed in keratinocytes, though neither fAd nor gAd had any effect on HA synthesis. In mouse skin, we found that adiponectin was present and decreased markedly with aging. The age-dependent pattern of adiponectin decrease in skin, correlated well with that of HA in skin. Our experiments were also the first to identify adiponectin production in cultured mouse sebocytes, a finding that suggests that skin adiponectin may derive not only from plasma and/or subcutaneous adipose tissue, but also from the sebaceous gland. These results indicated that adiponectin plays an important role in the HA metabolism of skin. PMID:21117904

  10. Identification of Adiponectin Receptor Agonist Utilizing a Fluorescence Polarization Based High Throughput Assay

    PubMed Central

    Sun, Yiyi; Zang, Zhihe; Zhong, Ling; Wu, Min; Su, Qing; Gao, Xiurong; Zan, Wang; Lin, Dong; Zhao, Yan; Zhang, Zhonglin

    2013-01-01

    Adiponectin, the adipose-derived hormone, plays an important role in the suppression of metabolic disorders that can result in type 2 diabetes, obesity, and atherosclerosis. It has been shown that up-regulation of adiponectin or adiponectin receptor has a number of therapeutic benefits. Given that it is hard to convert the full size adiponectin protein into a viable drug, adiponectin receptor agonists could be designed or identified using high-throughput screening. Here, we report on the development of a two-step screening process to identify adiponectin agonists. First step, we developed a high throughput screening assay based on fluorescence polarization to identify adiponectin ligands. The fluorescence polarization assay reported here could be adapted to screening against larger small molecular compound libraries. A natural product library containing 10,000 compounds was screened and 9 hits were selected for validation. These compounds have been taken for the second-step in vitro tests to confirm their agonistic activity. The most active adiponectin receptor 1 agonists are matairesinol, arctiin, (-)-arctigenin and gramine. The most active adiponectin receptor 2 agonists are parthenolide, taxifoliol, deoxyschizandrin, and syringin. These compounds may be useful drug candidates for hypoadiponectin related diseases. PMID:23691032

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

    PubMed

    Anuradha; Krishna, Amitabh

    2014-12-01

    The aim of this study was to evaluate the role of adiponectin in the delayed embryonic development of Cynopterus sphinx. Adiponectin receptor (ADIPOR1) abundance was first observed to be lower during the delayed versus non-delayed periods of utero-embryonic unit development. The effects of adiponectin treatment on embryonic development were then evaluated during the period of delayed development. Exogenous treatment increased the in vivo rate of embryonic development, as indicated by an increase in weight, ADIPOR1 levels in the utero-embryonic unit, and histological changes in embryonic development. Treatment with adiponectin during embryonic diapause showed a significant increase in circulating progesterone and estradiol concentrations, and in production of their receptors in the utero-embryonic unit. The adiponectin-induced increase in estradiol synthesis was correlated with increased cell survival (BCL2 protein levels) and cell proliferation (PCNA protein levels) in the utero-embryonic unit, suggesting an indirect effect of adiponectin via estradiol synthesis by the ovary. An in vitro study further confirmed the in vivo findings that adiponectin treatment increases PCNA levels together with increased uptake of glucose by increasing the abundance of glucose transporter 8 (GLUT8) in the utero-embryonic unit. The in vitro study also revealed that adiponectin, together with estradiol but not alone, significantly increased ADIPOR1 protein levels. Thus, adiponectin works in concert with estradiol to increase glucose transport to the utero-embryonic unit and promote cell proliferation, which together accelerate embryonic development. PMID:25295970

  12. The role of leptin in central nervous system diseases

    PubMed Central

    Li, Xiao-Mei; Yan, Hai-Jing; Guo, Yi-Shan

    2016-01-01

    Leptin is a peptide hormone produced by adipose tissue and acts in brain centers to control critical physiological functions. Leptin receptors are especially abundant in the hypothalamus and trigger specific neuronal subpopulations, and activate several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway. Although most studies focus on its role in energy intake and expenditure, leptin also plays a critical role in many central nervous system diseases. PMID:26885866

  13. Leptin and Reproduction: Past Milestones, Present Undertakings and Future Endeavors

    PubMed Central

    Chehab, Farid F.

    2014-01-01

    The association between leptin and reproduction originated with the leptin-mediated correction of sterility in ob/ob mice and initiation of reproductive function in normal female mice. The uncovering of a central leptin pathway regulating food intake prompted the dissection of neuroendocrine mechanisms involving leptin in the metabolic control of reproduction. The absence of leptin receptors on GnRH neurons incited a search for intermediary neurons situated between leptin responsive and GnRH neurons. This review addresses the most significant findings that have furthered our understanding of recent progress in this new field. The role of leptin in puberty was impacted by the discovery of neurons that co-express kisspeptin, neurokinin B and dynorphin and that could act as leptin intermediates. Furthermore, the identification of first-order leptin-responsive neurons in the premammilary ventral nucleus and other brain regions opens new avenues to explore their relationship to GnRH neurons. Central to these advances is the unveiling that AgRP/NPY neurons project onto GnRH and kisspeptin neurons, allowing a crosstalk between food intake and reproduction. Finally, whereas puberty is a state of leptin sensitivity, mid-gestation represents a state of leptin resistance aimed at building energy stores to sustain pregnancy and lactation. Mechanisms underlying leptin resistance in pregnancy have lagged, however the establishment of this natural state is significant. Reproduction and energy balance are tightly controlled and backed up by redundant mechanisms that are critical for the survival of our species. It will be the goal of the next decade to shed new light on these complex and essential pathways. PMID:25118207

  14. Leptin and its cardiovascular effects: Focus on angiogenesis

    PubMed Central

    Tahergorabi, Zoya; Khazaei, Majid

    2015-01-01

    Leptin is an endocrine hormone synthesized by adipocytes. It plays a key role in the energy homeostasis in central and peripheral tissues and has additional roles are attributed to it, such as the regulation of reproduction, immune function, bone homeostasis, and angiogenesis. The plasma concentration of leptin significantly increases in obese individuals. In the present review, we give an introduction concerning leptin, its receptors, signaling pathways, and its effect on cardiovascular system, especially on angiogenesis. PMID:26015905

  15. Leptin receptor gene expression and number in the brain are regulated by leptin level and nutritional status.

    PubMed

    Mitchell, Sharon E; Nogueiras, Ruben; Morris, Amanda; Tovar, Sulay; Grant, Christine; Cruickshank, Morven; Rayner, D Vernon; Dieguez, Carlos; Williams, Lynda M

    2009-07-15

    Hormone potency depends on receptor availability, regulated via gene expression and receptor trafficking. To ascertain how central leptin receptors are regulated, the effects of leptin challenge, high-fat diet, fasting and refeeding were measured on leptin receptor number and gene expression. These were measured using quantitative (125)I-labelled leptin in vitro autoradiography and in situ hybridisation, respectively. Ob-R (all forms of leptin receptor) expression in the choroid plexus (CP) was unchanged by high-fat diet or leptin challenge, whereas fasting increased but refeeding failed to decrease expression. (125)I-labelled leptin binding to the CP was increased by fasting and returned to basal levels on refeeding. (125)I-Labelled leptin was reduced by leptin challenge and increased by high-fat feeding. Ob-Rb (signalling form) in the arcuate (ARC) and ventromedial (VMH) nuclei was increased after fasting and decreased by refeeding. Leptin challenge increased Ob-Rb expression in the ARC, but not after high-fat feeding. In general, changes in gene expression in the ARC and VMH appeared to be largely due to changes in area rather than density of labelling, indicating that the number of cells expressing Ob-Rb was the parameter that contributed most to these changes. Leptin stimulation of suppressor of cytokine signalling 3 (SOCS3), a marker of stimulation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway, was unchanged after high-fat diet. Thus, early loss of leptin sensitivity after high-fat feeding is unrelated to down-regulation of leptin receptor expression or number and does not involve the JAK/STAT pathway. The effect of leptin to decrease (125)I-labelled leptin binding and the loss of ability of leptin to up-regulate Ob-Rb expression in the ARC after high-fat feeding offer potential mechanisms for the development of leptin insensitivity in response to both hyperleptinaemia and high-fat diet. PMID:19491239

  16. Inhibition of Leptin-ObR Interaction Does not Prevent Leptin Translocation Across a Human Blood-Brain Barrier Model.

    PubMed

    Gonzalez-Carter, D; Goode, A E; Fiammengo, R; Dunlop, I E; Dexter, D T; Porter, A E

    2016-06-01

    The adipocyte-derived hormone leptin regulates appetite and energy homeostasis through the activation of leptin receptors (ObR) on hypothalamic neurones; hence, leptin must be transported through the blood-brain barrier (BBB) to reach its target sites in the central nervous system. During obesity, however, leptin BBB transport is decreased, in part precluding leptin as a viable clinical therapy against obesity. Although the short isoform of the ObR (ObRa) has been implicated in the transport of leptin across the BBB as a result of its elevated expression in cerebral microvessels, accumulating evidence indicates that leptin BBB transport is independent of ObRa. In the present study, we employed an ObR-neutralising antibody (9F8) to directly examine the involvement of endothelial ObR in leptin transport across an in vitro human BBB model composed of the human endothelial cell line hCMEC/D3. Our results indicate that, although leptin transport across the endothelial monolayer was nonparacellular, and energy- and endocytosis-dependent, it was not inhibited by pre-treatment with 9F8, despite the ability of the latter to recognise hCMEC/D3-expressed ObR, prevent leptin-ObR binding and inhibit leptin-induced signal transducer and activator of transcription 3 (STAT-3) phosphorylation in hCMEC/D3 cells. Furthermore, hCMEC/D3 cells expressed the transporter protein low-density lipoprotein receptor-related protein-2 (LRP-2), which is capable of binding and endocytosing leptin. In conclusion, our results demonstrate that leptin binding to and signalling through ObR is not required for efficient transport across human endothelial monolayers, indicating that ObR is not the primary leptin transporter at the human BBB, a role which may fall upon LRP-2. A deeper understanding of leptin BBB transport will help clarify the exact causes for leptin resistance seen in obesity and aid in the development of more efficient BBB-penetrating leptin analogues. PMID:27037668

  17. Variants of resistin gene and the risk of idiopathic dilated cardiomyopathy in Pakistan

    PubMed Central

    Hussain, Sabir; Haroon, Javeria; Ejaz, Shagufta; Javed, Qamar

    2016-01-01

    Background In cardiovascular disease phenotypes, a genetic factor is an important determinant of both familial and non-familial dilated cardiomyopathies. Resistin is a novel adipocyte derived peptide, associated with inflammation and suggested to be involved in contractile abnormalities of cardiomyocytes. Methods In this study, we examined the association of the RETN SNPs in − 420 and + 299 in patients with idiopathic dilated cardiomyopathy (IDCM). Patients with IDCM (n = 250) and healthy controls (n = 250) were enrolled in this study. RETN genotyping was performed by using PCR-RFLP method. Results RETN − 420C > G and + 299G > A polymorphisms were significantly more prevalent in patient group vs. controls (P < 0.0001 and P = 0.0007, respectively). GG genotype at − 420 and AA genotype at + 299 were higher in the patient group compared with healthy controls (OR = 11.4, P < 0.0001, and OR = 2.3, P = 0.030, respectively). We found that the − 420G allele increased the risk of developing IDCM in patients (P < 0.0001). Moreover, there was a significant difference between G and A alleles at RETN + 299 from IDCM cases and controls (P = 0.0032). The RETN − 420G and + 299A haplotypes were more prevalent in the patient vs. control group (P < 0.0001). Conclusion The results suggest that the RETN − 420C > G and + 299G > A polymorphisms may have a role in the pathogenesis of IDCM. PMID:27114921

  18. Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance.

    PubMed

    Axelsson, J; Bergsten, A; Qureshi, A R; Heimbürger, O; Bárány, P; Lönnqvist, F; Lindholm, B; Nordfors, L; Alvestrand, A; Stenvinkel, P

    2006-02-01

    In the present study, we explore the role of decreased renal function and a genetic polymorphism on the recently discovered protein resistin, apparently able to inhibit hepatic insulin action in mice. We also investigate possible links with inflammation and the insulin resistance present in patients with chronic kidney disease (CKD). This is a post hoc, cross-sectional study comparing 239 prevalent CKD patients with varying degrees of renal function impairment with an age- and gender-matched randomly selected control group of 25 individuals. Glomerular filtration rate (GFR) was estimated by the mean of urea and creatinine clearance (24-h urine samples) (n=204) or by iohexol clearance (n=60). Plasma analysis of blood lipids, insulin, glucose, inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, vascular cellular adhesion molecule, intercellular adhesion molecule) and resistin (kit from LINCO Research, St Charles, MS) was performed using commercially available assays or routine methods. Insulin resistance was estimated by quantitative insulin-sensitivity check index (QUICKI) and homeostasis model assessment for insulin resistance (HOMA-IR) and body composition by dual-energy X-ray absorptiometry. Genotyping of a C/G promoter single nucleotide polymorphism (n=168) at position -180 of the resistin gene was performed by PyroSequencing. Serum levels of resistin were markedly elevated in the CKD patients with both advanced (39.9+/-1.3 ng/ml) and mild to moderate (23.2+/-1.0 ng/ml) renal function impairment, as compared to controls (8.5+/-0.7 ng/ml; P<0.001). In a multiple linear regression model in patients (adjusted r(2)=0.60), only GFR (beta=3.4; P<0.0001), lean body mass (beta=2.2; P<0.001) and the inflammatory markers were independently associated with circulating resistin levels. There was a weak but significant impact of -180 C/G genotype on plasma levels of resistin (median 43.0+/-2.4 ng/ml in CC, 37.5+/-2.0 ng

  19. Peritoneal clearance of leptin in continuous ambulatory peritoneal dialysis.

    PubMed

    Arkouche, W; Juillard, L; Delawari, E; Lasne, Y; Combarnous, F; Sibaï-Galland, R; Traeger, J; Laville, M; Fouque, D

    1999-11-01

    Leptin is a 16-kd protein that increases energy expenditure and limits food intake. Serum leptin (S-leptin) is elevated in dialysis patients, and little data have been reported on leptin clearance (Cl) during dialysis. We analyzed the peritoneal dialysis (PD) Cl of leptin in 15 continuous ambulatory peritoneal dialysis (CAPD) patients and compared the results to beta(2)-microglobulin (beta(2)-m), urea, and creatinine PD Cl. S-leptin was significantly elevated (Kruskal-Wallis, P < 0.005) in CAPD women (58.4 +/- 42.4 [SE] microg/L, n = 5) as compared with CAPD men (13.9 +/- 7.1, n = 10) and with healthy women (11.0 +/- 1.4, n = 13) and men (5.1 +/- 0. 9, n = 14). Correlations were found between percent of fat mass and S-leptin (P < 0.05); between S-leptin and the 24-hour PD leptin (P < 0.05); and between dialysate-to-plasma (D/P) beta(2)-m and D/P leptin (P < 0.01). PD leptin Cl (1.80 +/- 0.43 mL/min/1.73 m(2)) was higher than beta(2)-m Cl (1.22 +/- 0.31) (P < 0.01), but reduced as compared with urea Cl (8.84 +/- 1.20) (P < 0.005) and creatinine Cl (7.71 +/- 0.99) (P < 0.005). These results indicate that leptin is eliminated through the peritoneum membrane. However, peritoneal leptin clearance, as beta(2)-m, appears to be clearly restricted as compared with peritoneal transport of smaller molecules. Hence, leptin could use the same diffusion transport pathway as beta(2)-m. In addition, leptin, which has a higher molecular weight than beta(2)-m, was significantly more eliminated into the peritoneal dialysate. More studies are necessary to clarify whether this is an active leptin elimination process by peritoneal secretion or by a different restriction coefficient of diffusion through the peritoneum membrane. PMID:10561139

  20. Lean heart: Role of leptin in cardiac hypertrophy and metabolism

    PubMed Central

    Hall, Michael E; Harmancey, Romain; Stec, David E

    2015-01-01

    Leptin is an adipokine that has been linked with the cardiovascular complications resulting from obesity such as hypertension and heart disease. Obese patients have high levels of circulating leptin due to increased fat mass. Clinical and population studies have correlated high levels of circulating leptin with the development of cardiac hypertrophy in obesity. Leptin has also been demonstrated to increase the growth of cultured cardiomyocytes. However, several animal studies of obese leptin deficient mice have not supported a role for leptin in promoting cardiac hypertrophy so the role of leptin in this pathological process remains unclear. Leptin is also an important hormone in the regulation of cardiac metabolism where it supports oxidation of glucose and fatty acids. In addition, leptin plays a critical role in protecting the heart from excess lipid accumulation and the formation of toxic lipids in obesity a condition known as cardiac lipotoxicity. This paper focuses on the data supporting and refuting leptin’s role in promoting cardiac hypertrophy as well as its important role in the regulation of cardiac metabolism and protection against cardiac lipotoxicity. PMID:26413228

  1. Leptin mRNA expresses in the bull reproductive organ.

    PubMed

    Abavisani, A; Baghbanzadeh, A; Shayan, P; Tajik, P; Dehghani, H; Mirtorabi, M

    2009-12-01

    Leptin, a 167-amino acid hormone, is secreted mainly by fat tissue. It has some powerful effects on the regulation of metabolism and reproductive function through endocrine and probably paracrine mechanisms. The contribution rate of leptin function on the male reproductive system is not still clear. Characterization of leptin expression in reproductive organs will suggest that in addition to its endocrine action, leptin has also paracrine/autocrine effects on reproduction. The expression of functional leptin receptor mRNA has been already recognized in testis of rodents, human and cattle. Thus, the aim of the present study was to investigate the presence of leptin mRNA in the bovine testis, because it will be the first step for understanding of its paracrine/autocrine effects on the male reproductive organs in cattle. The present study was the first to showed leptin mRNA expression in the testis of Holstein cattle using reverse transcription and polymerase chain reaction (RT-PCR) analysis. RT-PCR products were amplified with nested PCR using inner leptin primer pairs to emphasis the first results. Besides, bovine beta actin gene was acted as an internal positive control as well as RNA purification marker. Our findings suggest that in addition to its endocrine actions at the hypothalamic-pituitary axis, leptin can has an autocrine and/or paracrine role in bull testicular function. PMID:19466574

  2. Role of C Reactive Protein (CRP) in Leptin Resistance

    PubMed Central

    Hribal, Marta Letizia; Fiorentino, Teresa Vanessa; Sesti, Giorgio

    2014-01-01

    Increased plasma levels of both leptin and C reactive protein (CRP) have been reported in a number of conditions, including obesity, and have been linked to cardiovascular pathophysiological processes and increased cardiovascular risk; interestingly these two biomarkers appear to be able to reciprocally regulate their bioavailability, through complex mechanisms that have not been completely clarified yet. Here we first review clinical evidence suggesting not only that the circulatory levels of CRP and leptin show an independent correlation, but also that assessing them in tandem may result in an increased ability to predict cardiovascular disease. We summarize also molecular studies showing that leptin is able to promote CRP production from hepatocytes and endothelial cells in vitro and discuss the studies addressing the possibility that in vivo leptin administration may be able to modulate plasma CRP levels. Furthermore, we describe two studies demonstrating that CRP directly binds leptin in extra-cellular settings, thus impairing its biological actions. Finally we report genetic evidence that common variations at the leptin receptor locus are associated with CRP blood levels. Overall, the data reviewed here show that the chronic elevation of CRP observed in obese subjects may worsen leptin resistance, contributing to the pathogenesis of cardiovascular disease, and highlight a potential link between conditions, such as leptin resistance and endothelial dysfunction, that may be amenable of pharmacological treatment targeted to the disruption of leptin-CRP interaction. PMID:23688010

  3. Leptin as a potential treatment for obesity: progress to date.

    PubMed

    Bell-Anderson, Kim S; Bryson, Janet M

    2004-01-01

    Despite significant reductions in the consumption of dietary fat, the prevalence of obesity is steadily rising in western civilization. Of particular concern is the recent epidemic of childhood obesity, which is expected to increase the incidence of obesity-related disorders. The obese gene (ob) protein product leptin is a hormone that is secreted from adipocytes and functions to suppress appetite and increase energy expenditure. Leptin is an attractive candidate for the treatment of obesity as it is an endogenous protein and has been demonstrated to have potent effects on bodyweight and adiposity in rodents. Whereas leptin has been successfully used in the treatment of leptin-deficient obese patients, trials in hyperleptinemic obese patients have yielded variable results. Long-acting leptins have been tried but with no greater success. Other strategies including the use of leptin analogs and other factors that bypass normal leptin delivery systems are being developed. Identifying the mechanisms at the molecular level by which leptin functions will create new avenues for pharmaceutical targeting to simulate the intracellular effects of leptin. PMID:15743109

  4. Association of adiponectin and adiponectin receptor genes with sow productivity estimated breeding values.

    PubMed

    Jafarikia, Moshen; Méthot, Steve; Maignel, Laurence; Fortin, Frédéric; Wyss, Stefanie; Sullivan, Brian; Palin, Marie-France

    2015-09-01

    Our objectives were to estimate frequencies of previously identified single nucleotide polymorphisms (SNPs) in adiponectin (ADIPOQ) and its receptors (ADIPOR1 and ADIPOR2) in a population of Duroc, Landrace and Yorkshire pigs and evaluate the effect of these alleles on sow productivity estimated breeding values (EBVs). Eight SNPs were genotyped on 446 pigs in the ADIPOQ (c.178G>A, c.*300A>G, c.*1094_1095insC and c.*1779A>C), ADIPOR1 (c.*129A>C) and ADIPOR2 (c.*112G>A, c.*295G>C and c.*1455G>A) genes. Association analyses were performed with sow productivity EBVs based on litter records collected in Canadian breeding farms. There were significant associations between ADIPOQ c.178G>A and c.*1094_1095insC SNPs and studied traits. However, none of these associations remained significant after applying a Bonferroni correction. The ADIPOR2 c.*112G>A SNP was associated with the total number of piglets born (TNB, P < 0.001) and litter weight at weaning (LWW, P < 0.001) EBVs. Associations were also observed between the ADIPOR2 [A;C;G] haplotype and TNB and LWW (P < 0.001). Our results demonstrate that a selection in favor of the c.*112G allele or against the [A;C;G] haplotype may have the potential to increase LWW EBVs. However, the c.*112G allele is also associated with lower TNB EBVs. Some of the alleles of the genes studied showed substantial variability and in general, the results corroborated previously reported findings for an independent sow population. However, careful cost-benefits analyses should be performed before using these markers in selection program as an improvement in TNB may translate into lighter LWW, with its associated negative impact on production traits such as growth performances. PMID:26210991

  5. Correlation between serum adiponectin and clinical characteristics, biochemical parameters in Indian women with polycystic ovary syndrome

    PubMed Central

    Ramanand, Sunita J.; Ramanand, Jaiprakash B.; Ghongane, Balasaheb B.; Patwardhan, Milind H.; Patwardhan, Varsha M.; Ghanghas, Ravi; Halasawadekar, Nimish R.; Patil, Praveenkumar

    2014-01-01

    Background: Polycystic ovary syndrome (PCOS) is a common disorder. PCOS women are at a high risk for insulin resistance and metabolic syndrome (MS). Adiponectin is positively related to insulin sensitivity. It has a preventive role in atherogenesis and MS. The present work was conducted to study the correlation between serum adiponectin levels and clinical characteristics and biochemical parameters in PCOS patients. Materials and Methods: A prospective study in 49 newly diagnosed (as per Rotterdam criteria) Indian PCOS women was conducted. PCOS women were clinically examined and investigated for biochemical parameters. Results: The mean serum adiponectin was 12 ± 9.4 μg/mL (range 0.47-45). Hypoadiponectinemia (serum adiponectin <4 μg/mL) was present in 22% patients. Age and adiponectin correlated significantly and inversely (r = −0.42, P = 0.027). Overweight/obese patients had lower mean adiponectin levels than normal weight (11.62 ± 9.5 vs 13.58 ± 9.5, P = 0.56). It was significantly lower in patients with acanthosis nigricans (AN) as compared with those without AN (8.4 ± 5.9 vs 15 ± 11, P = 0.038). Hirsute patients showed lower mean adiponectin levels than nonhirsute (10 ± 7.3 vs 13 ± 10, P = 0.57). A positive, insignificant correlation was observed between serum adiponectin and cholesterol, low-density lipoprotein, follicle stimulating hormone (FSH), thyroid stimulating hormone, levels. A negative insignificant correlation existed between serum adiponectin and luteinizing hormone (LH), LH: FSH ratio, prolactin, dehydroepiandrosterone, testosterone, triglyceride, high-density lipoprotein, fasting blood glucose, fasting insulin, and Homeostasis Model Assessment. Conclusion: Hypoadiponectinemia is present in one-fifth of women with PCOS. Adiponectin levels decrease as age advances. Low levels of adiponectin possibly contributes to the development of dermal manifestation (AN) of insulin resistance. PMID:24741521

  6. Effect of conjugated linoleic acid on body fat, tumor necrosis factor alpha and resistin secretion in spontaneously hypertensive rats.

    PubMed

    Hernández-Díaz, Guillermo; Alexander-Aguilera, Alfonso; Arzaba-Villalba, Agustin; Soto-Rodríguez, Ida; García, Hugo S

    2010-01-01

    Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivaties of linoleic acid found mainly in beef and dairy products. CLA has been reported to reduce body fat, as well as to possess anticarcinogenic, antiatherogenic and procatabolic activities in animals. The objective of this study was to evaluate the effect of CLA supplementation to spontaneously hypertensive rats (SHR) on body fat, biochemical parameters of serum related tumor necrosis factor alpha (TNF-alpha) and resistin secretion. Thirty rats were divided in three groups, the first group of spontaneously hypertensive rats received a standard diet (V-SHR group, n=10), a second group of SHR was fed 1.5% of conjugated linoleic acid (CLA-SHR group, n=10) and the third was the control, non-hypertensive group (KW, n=10) also on a standard diet including 7.5% of sunflower oil during eight weeks. After CLA diet administration, spontaneously hypertensive rats showed a significant reduction in blood pressure, serum glucose, cholesterol and triacylglycerols, together with reduction of index of body fat, pericardic, abdominal and epididymal adipose tissue. These effects were accompanied by a decrease in the secretion of TNF-alpha and resistin. PMID:20074923

  7. The Association of Serum Leptin with Mortality in Older Adults

    PubMed Central

    Harris, Tamara B.; Hsueh, Wen-Chi; Hue, Trisha; Leak, Tennille S.; Li, Rongling; Mehta, Mira; Vaisse, Christian

    2015-01-01

    Objective Elevated levels of serum leptin are associated with increased adiposity and production of pro-inflammatory cytokines. Both cytokines and body adiposity have been shown to predict cardiovascular events and mortality. The primary objective of the present study is to explore the associations between serum leptin and all-cause mortality and mortality from cardiovascular disease (CVD) over a span of 10 years, controlling for body adiposity and proinflammatory cytokines. Methods The Health, Aging and Body Composition (Health ABC) study is a prospective cohort of 3,075 older adults aged 70 to 79 years. This analysis includes 2,919 men and women with complete serum leptin and vital status data. Data on all-cause mortality and incident cardiovascular events (including Coronary Heart Disease and Congestive Heart Failure) were collected over 10 years of follow-up (mean 8.4 years). Results Women with leptin in quartile 2 and 3 were at lower risk of all-cause mortality, and those with leptin in quartile 2 were at lower risk of mortality from CVD as compared to women with lowest leptin values when adjusted for age, race, site, years of education, alcohol use, smoking, and physical activity. When these associations were additionally adjusted for body fat, C-reactive protein and pro-inflammatory cytokines, women with leptin values in quartile 3 were at lower risk of all-cause mortality and women with leptin in quartile 2 and 3 were at lower risk of mortality from CVD than women with lowest leptin values. These associations were not significant among men after adjusting for body fat and cytokines. Conclusions The present study suggests that moderately elevated concentrations of serum leptin are independently associated with lower risk of all-cause mortality and CVD-related mortality among older women. Among men, serum leptin is not associated with reduced risk of all-cause and CVD mortality after controlling for body fat and cytokines. PMID:26473487

  8. Plasma leptin values in postmenopausal women with osteoporosis.

    PubMed

    Kocyigit, Hikmet; Bal, Serpil; Atay, Ayşenur; Koseoglu, Mehmet; Gurgan, Alev

    2013-08-01

    Obesity has a protective effect against osteoporosis and this effect has been attributed to a high body fat content. It has been shown that the leptin concentration is higher in obese patients. Leptin, the protein product of obesity gene, is a hormone produced in adipose tissue. Some studies suggest that endogenous leptin might influence bone metabolism in postmenopausal women. In this study, we investigated plasma leptin concentrations in postmenopausal women with osteoporosis and also analyzed the relationship between plasma leptin levels and bone mineral density (BMD) in order to understand the potential role of leptin in maintaining bone mass. Forty-two postmenopausal women with osteoporosis and thirty seven age and BMI-matched healthy postmenopausal women were included in the study. The mean femoral neck BMD value in the patient group was significantly lower than that in the control group (0.691±0.1 g/cm2 and 0.863±0.1 g/cm2, respectively; p<0.001). The mean plasma leptin concentration in the patient group was not significantly different from that in the control group (p>0.05). Plasma leptin levels were correlated with BMI in both groups (p<0.001 in the patient group and p=0.001 in controls). There was also a strong positive correlation between plasma leptin levels and %fat in both groups (p<0.001 in the patient group and p<0.001 in controls). But there was no correlation between plasma leptin levels and femoral neck BMD values in both groups. Our results do not support the hypothesis that leptin itself plays an important role in maintaining bone mass in postmenopausal women. PMID:23988172

  9. [Serum leptin in women during the third trimester of pregnancy].

    PubMed

    Stejskal, D; Růzicka, V; Novák, J; Jedelský, L; Bartek, J; Horalík, D

    1998-10-01

    Leptin is a small protein produced mainly by adipocytes. Recently, its relationship to obesity has been studied extensively. It was proved that obese individuals have either relative or absolute leptin deficiency. Several years ago, leptin was found to be produced also by the placenta. This stimulated us to study relationship between leptinemia and placental hormones in 85 women in the second gravidity trimester. Within the prenatal screening, these pregnant women were subjected to analysis of AFP, hCG, SP-1 glycoprotein and leptin and the results obtained were processed statistically. The control group consisted of 20 nonpregnant women with tetany. Women in the second gravidity trimester were found to have a significantly higher leptinemia than nongravid women (even with respect to body weight). This may be due to a larger amount of adipose tissue during gravidity and also leptin-resistance. Moreover, we recorded a negative correlation between leptinemia related to body weight and concentration of SP-1 glycoprotein. This finding supports the presumption that mother's leptinemia correlated negatively in the second gravidity trimester with quality and quantity of the placental syncytiotrophoblast. Our findings can be explained as follows: the biological effect of leptin is metabolically unfavourable for the growth of the foetus and the placenta. An increased leptinemia with advancing gravidity can be caused by a larger fatty mass and an increased activity of adipocytes when leptin presence increases in system circulation but the organism begins to be leptin-resistant and an "unfavourable" metabolic effect fort the gravid woman and the foetus is not distinct. These findings thus support the hypothesis postulating the nonsignificance of leptin production in human placenta and on the contrary the necessity of leptin-resistance for foetus development from the metabolic point of view. Thus, a decreased leptinemia immediately before and after the delivery could be caused

  10. Onset of leptin resistance shows temporal differences related to dose or pulsed treatment.

    PubMed

    Strehler, Kevin Y E; Matheny, Michael; Kirichenko, Nataliya; Sakarya, Yasemin; Bruce, Erin; Toklu, Hale Zerrin; Carter, Christy S; Morgan, Drake; Tümer, Nihal; Scarpace, Philip J

    2016-05-15

    Leptin administration results in leptin resistance presenting a significant barrier to therapeutic use of leptin. Consequently, we examined two hypotheses. The first examined the relationship between leptin dose and development of physiological and biochemical signs of leptin resistance. We hypothesized lower doses of leptin would produce proportional reductions in body weight without the adverse leptin-induced leptin resistance. The second compared pulsed central leptin infusion to continuous leptin infusion. We hypothesized that pulsed infusion at specific times of the day would evoke favorable body weight reductions while tempering the development of leptin-induced leptin resistance. The first experiment examined leptin responsiveness, including food intake, body weight and hypothalamic STAT3 phosphorylation to increasing doses of viral gene delivery of leptin. Varying the dose proved inconsequential with respect to long-term therapy and demonstrated proportional development of leptin resistance. The second experiment examined leptin responsiveness to pulsed central leptin infusion, comparing pulsed versus constant infusion of 3μg/day leptin or a 2h morning versus a 2h evening pulsed leptin infusion. Pulsed delivery of the supramaximal dose of 3μg/day was not different than constant delivery. Morning pulsed infusion of the submaximal dose of 0.25μg reduces food intake only over subsequent immediate meal period and was associated with body weight reductions, but results in cellular leptin resistance. Evening pulsed infusion did not decrease food intake but reduces body weight and maintains full leptin signaling. The positive benefit for pulsed delivery remains speculative, yet potentially may provide an alternative mode of leptin therapy. PMID:27012992

  11. Effect of Maternal Body Mass Index on Hormones in Breast Milk: A Systematic Review

    PubMed Central

    Andreas, Nicholas J.; Hyde, Matthew J.; Gale, Chris; Parkinson, James R. C.; Jeffries, Suzan; Holmes, Elaine; Modi, Neena

    2014-01-01

    Background Maternal Body Mass Index (BMI) is positively associated with infant obesity risk. Breast milk contains a number of hormones that may influence infant metabolism during the neonatal period; these may have additional downstream effects on infant appetite regulatory pathways, thereby influencing propensity towards obesity in later life. Objective To conduct a systematic review of studies examining the association between maternal BMI and the concentration of appetite-regulating hormones in breast milk. Method Pubmed was searched for studies reporting the association between maternal BMI and leptin, adiponectin, insulin, ghrelin, resistin, obestatin, Peptide YY and Glucagon-Like Peptide 1 in breast milk. Results Twenty six studies were identified and included in the systematic review. There was a high degree of variability between studies with regard to collection, preparation and analysis of breast milk samples. Eleven of fifteen studies reporting breast milk leptin found a positive association between maternal BMI and milk leptin concentration. Two of nine studies investigating adiponectin found an association between maternal BMI and breast milk adiponectin concentration; however significance was lost in one study following adjustment for time post-partum. No association was seen between maternal BMI and milk adiponectin in the other seven studies identified. Evidence for an association between other appetite regulating hormones and maternal BMI was either inconclusive, or lacking. Conclusions A positive association between maternal BMI and breast milk leptin concentration is consistently found in most studies, despite variable methodology. Evidence for such an association with breast milk adiponectin concentration, however, is lacking with additional research needed for other hormones including insulin, ghrelin, resistin, obestatin, peptide YY and glucagon-like peptide-1. As most current studies have been conducted with small sample sizes, future studies

  12. Adiponectin exerts antiproliferative effect on human placenta via modulation of the JNK/c-Jun pathway

    PubMed Central

    Chen, Haitian; Chen, Hanqing; Wu, Yanxin; Liu, Bin; Li, Zhuyu; Wang, Zilian

    2014-01-01

    To determine the effects of adiponectin on human placenta during gestational diabetes mellitus (GDM) and on high glucose (HG)-induced BeWo cell proliferation. We examined the expression levels of adiponectin in control and GDM placenta using quantitative real-time PCR, Western blot, and immunohistochemistry (IHC). Cell proliferation and viability were assessed using a colorimetric assay (cell counting kit-8), PCNA immunocytochemical staining, and Western blot analysis of cyclin D1. Transfection of siRNA against c-jun was performed using Lipofectamine 2000. Cell cycle analysis was performed using propidium iodide staining and flow cytometry. Results show a decreased expression of adiponectin and an increased degree of trophoblast cell proliferation in GDM placenta compared to the normal placenta. Similarly, HG can promote BeWo cell proliferation that is associated with adiponectin down-regulation. This proliferation could be depressed by addition of exogenous adiponectin, i.e. adiponectin exerts antiproliferative effects on HG-induced trophoblast cells. Adiponectin suppresses the HG-induced BeWo cell proliferation by inhibiting the activation of JNK/c-jun. In conclusion, adiponectin inhibits HG-induced proliferation of BeWo cells through down-regulation of JNK/c-jun phosphorylation. PMID:25031708

  13. Globular adiponectin reduces vascular calcification via inhibition of ER-stress-mediated smooth muscle cell apoptosis

    PubMed Central

    Lu, Yan; Bian, Yunfei; Wang, Yueru; Bai, Rui; Wang, Jiapu; Xiao, Chuanshi

    2015-01-01

    Objective: This study aims to explore the mechanism of globular adiponectin inhibiting vascular calcification. Methods: We established drug-induced rat vascular calcification model, globular adiponectin was given to observe the effect of globular Adiponectin on the degree of calcification. The markers of vascular calcification and apoptosis were also investigated. Meanwhile, the in vitro effect of globular Adiponectin on vascular calcification was also evaluated using primary cultured rat vascular smooth muscle cells. Results: We found that globular adiponectin could inhibit drug-induced rat vascular calcification significantly in vivo. The apoptosis of vascular smooth muscle cells was also reduced. The possible mechanism could be the down-regulation of endoplasmic reticulum stress by globular adiponectin. Experiments in primary cultured vascular smooth muscle cells also confirmed that globular adiponectin could reduce cell apoptosis to suppress vascular calcification via inhibition of endoplasmic reticulum stress. Conclusions: This study confirmed that globular adiponectin could suppress vascular calcification; one of the mechanisms could be inhibition of endoplasmic reticulum stress to reduce cell apoptosis. It could provide an effective method in the therapy of vascular calcification-associated diseases. PMID:26045760

  14. Obesity-induced DNA hypermethylation of the adiponectin gene mediates insulin resistance

    PubMed Central

    Kim, A. Young; Park, Yoon Jeong; Pan, Xuebo; Shin, Kyung Cheul; Kwak, Soo-Heon; Bassas, Abdulelah F.; Sallam, Reem M.; Park, Kyong Soo; Alfadda, Assim A.; Xu, Aimin; Kim, Jae Bum

    2015-01-01

    Adiponectin plays a key role in the regulation of the whole-body energy homeostasis by modulating glucose and lipid metabolism. Although obesity-induced reduction of adiponectin expression is primarily ascribed to a transcriptional regulation failure, the underlying mechanisms are largely undefined. Here we show that DNA hypermethylation of a particular region of the adiponectin promoter suppresses adiponectin expression through epigenetic control and, in turn, exacerbates metabolic diseases in obesity. Obesity-induced, pro-inflammatory cytokines promote DNMT1 expression and its enzymatic activity. Activated DNMT1 selectively methylates and stimulates compact chromatin structure in the adiponectin promoter, impeding adiponectin expression. Suppressing DNMT1 activity with a DNMT inhibitor resulted in the amelioration of obesity-induced glucose intolerance and insulin resistance in an adiponectin-dependent manner. These findings suggest a critical role of adiponectin gene epigenetic control by DNMT1 in governing energy homeostasis, implying that modulating DNMT1 activity represents a new strategy for the treatment of obesity-related diseases. PMID:26139044

  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. 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:...

  17. The Role of Adiponectin in Cardiometabolic Diseases: Effects of Nutritional Interventions.

    PubMed

    Lopez-Jaramillo, Patricio

    2016-02-01

    Adiponectin is an adipocyte-derived hormone abundantly present in plasma that exerts its effects through the activation of 3 receptors. Its concentrations are negatively regulated by the accumulation of visceral fat, and clinical studies implicate hypoadiponectinemia in the pathogenesis of diabetes mellitus type 2, coronary artery disease, hypertension, and left ventricular hypertrophy. In contrast, high concentrations of adiponectin are associated with a decreased risk of coronary artery disease, with an improvement in the differentiation of preadipocytes into adipocytes, and with increased endothelial nitric oxide production. Therefore, adiponectin appears to be an important molecule involved in limiting the pathogenesis of obesity-linked disorders, and it may have potential benefits in the treatment and prevention of cardiovascular disease. Caloric restriction, moderate alcohol consumption, and consuming a Mediterranean diet increase adiponectin concentrations, and current evidence suggests a positive, dose-dependent relation between ω-3 (n-3) fatty acid intake and circulating concentrations of adiponectin. Recently, it was reported that the administration of aged garlic extract and a single food intervention with pistachios can increase adiponectin concentrations in individuals with metabolic syndrome. Moreover, the Mediterranean diet is associated with higher adiponectin concentrations. Additional studies are needed to evaluate the potential benefits of increasing adiponectin by nutritional interventions in the treatment and prevention of cardiometabolic diseases. PMID:26764331

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

    PubMed

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

    2016-09-15

    Adiponectin has been shown to suppress hepatic gluconeogenesis. However, the signaling pathways underlying its action remain ill-defined. The purpose of this study was to examine the potential role of APPL1 in mediating anti-gluconeogenic ability of adiponectin. Primary hepatocytes were isolated from male C57BL/6 mice. Western blot and RT-PCR were performed to detect protein expression and mRNA level, respectively. The protein-protein association was determined by immunoprecipitation and GST pull-down assay. We found that APPL1 protein levels were negatively associated with expressions of proteins and mRNAs of gluconeogenesis enzymes under stimulation with adiponectin. In addition, adiponectin-stimulated STAT3 phosphorylation and acetylation were positively regulated by APPL1 and negative regulated by SirT1. Pharmacological and genetic inhibition of STAT3 mitigated impact of adiponectin on hepatic gluconeogenesis. Furthermore, adiponectin administration facilitated the binding of APPL1 to SirT1 and suppressed the association of SirT1 with STAT3. Taken together, our study showed that APPL1-SirT1-STAT3 pathway mediated adiponectin signaling in primary hepatocytes. This new finding provides a novel mechanism by which adiponectin suppresses hepatic gluconeogenesis. PMID:27246173

  19. Adiponectin exacerbates collagen-induced arthritis via enhancing Th17 response and prompting RANKL expression.

    PubMed

    Sun, Xiaoxuan; Feng, Xiaoke; Tan, Wenfeng; Lin, Na; Hua, Minhui; Wei, Yu; Wang, Fang; Li, Ningli; Zhang, Miaojia

    2015-01-01

    We previously reported adiponectin (AD) is highly expressed in the inflamed synovial joint tissue and correlates closely with progressive bone erosion in Rheumatoid arthritis (RA) patients. Here, we investigate the role of adiponectin in regulating Th17 response and the expression of receptor activator of nuclear factor-κB ligand (RANKL) in mice with CIA mice by intraarticularly injection of adiponectin into knee joints on day 17, day 20 and day 23 post first collagen immunization. The increased adiponectin expression was found in inflamed joint tissue of collagen-induced arthritis (CIA) mice. Adiponectin injection resulted in an earlier onset of arthritis, an aggravated arthritic progression, more severe synovial hyperplasia, bone erosion and osteoporosis in CIA mice. CD4(+)IL-17(+) Th17 cells, IL-17 mRNA and RANKL mRNA expression were markedly increased in the joint tissue of adiponectin treated CIA mice. Moreover, adiponectin treatment markedly enhanced Th17 cell generation from naive CD4(+) T cells in vitro, which accompanied by the high expression of Th17 transcription factor ROR-γt, and Th17 cytokine genes included IL-22 and IL-23. This study reveals a novel effect of adiponectin in exacerbating CIA progression by enhancing Th17 cell response and RANKL expression. PMID:26063682

  20. Subattomole detection of adiponectin in urine by ultrasensitive ELISA coupled with thio-NAD cycling

    PubMed Central

    Morikawa, Mika; Naito, Rina; Mita, Koichi; Watabe, Satoshi; Nakaishi, Kazunari; Yoshimura, Teruki; Miura, Toshiaki; Hashida, Seiichi; Ito, Etsuro

    2015-01-01

    Adiponectin is a hormone secreted from adipocytes, and it demonstrates antidiabetic, anti-atherosclerotic, antiobesity and anti-inflammatory effects. However, the patterns of change in urinary adiponectin levels in various diseases remain unknown, because only trace amounts of the hormone are present in urine. In the present study, we applied an ultrasensitive ELISA coupled with thio-NAD cycling to measure urinary adiponectin levels. Spikeand-recovery tests using urine confirmed the reliability of our ultrasensitive ELISA. The limit of detection for adiponectin in urine was 2.3×10−19 moles/assay (1.4 pg/mL). The urinary adiponectin concentration ranged between 0.04 and 5.82 ng/mL in healthy subjects. The pilot study showed that the urinary adiponectin levels, which were corrected by the creatinine concentration, were 0.73±0.50 (ng/mg creatinine, N=6) for healthy subjects, versus 12.02±3.85 (ng/mg creatinine, N=3) for patients with diabetes mellitus (DM). That is, the urinary adiponectin levels were higher (P<0.05) in DM patients than in healthy subjects. Further, these urinary adiponectin levels tended to increase with the progression of DM accompanied with nephropathy. Our method is thus expected to provide a simple, rapid and reasonably priced test for noninvasive monitoring of the progression of DM without the requirement of special tools.

  1. Modulation of intestinal L-glutamate transport by luminal leptin.

    PubMed

    Fanjul, Carmen; Barrenetxe, Jaione; Lostao, María Pilar; Ducroc, Robert

    2015-06-01

    Leptin is secreted into the digestive tract and contributes to the absorption of dietary molecules by regulating transporters activity. Here, we studied the effect of luminal leptin on the intestinal transport of L-glutamate, an important component of human diet. We examined the effect of leptin on L-glutamate uptake in rat intestine in vitro measuring glutamate-induced short-circuit current (Isc) in Ussing chambers and L-[(3)H (U)]-glutamate uptake in jejunal everted rings. Glutamate-induced Isc was only observed in Na(+)-free conditions. This Isc was concentration (1-60 mmol L(-1)) and pH dependent. Luminal leptin increased glutamate Isc (∼100 %). Dose-response curve showed a biphasic pattern, with maximal stimulations observed at 10(-13) and 10(-10) mmol L(-1), that were sensitive to leptin receptor antagonist. In everted rings, two glutamate transport mechanisms were distinguished: a Na(+)-dependent, H(+)-independent, that was inhibited by leptin (∼20 %), and a Na(+)-independent but H(+)-dependent, that was enhanced by leptin (∼20 %), in line with data obtained in Ussing chambers. Altogether, these data reveal original non-monotonic effect of luminal leptin in the intestine and demonstrate a new role for this hormone in the modulation of L-glutamate transport, showing that luminal active gut peptides can influence absorption of amino acids. PMID:25935421

  2. Hypothalamic sites of leptin action linking metabolism and reproduction.

    PubMed

    Donato, José; Cravo, Roberta M; Frazão, Renata; Elias, Carol F

    2011-01-01

    A critical amount of energy reserve is necessary for puberty initiation, for normal sexual maturation and maintenance of cyclicity and fertility in females of most species. Therefore, the existence of circulating metabolic cues which directly modulate the hypothalamus-pituitary-gonad axis is predictable. The adipocyte-derived hormone leptin is one of these cues having been studied extensively in the context of regulating the reproductive physiology. Humans and mice lacking leptin (ob/ob) or leptin receptor (LepR, db/db) are infertile. Leptin administration to leptin-deficient subjects and ob/ob mice induces puberty and restores fertility. LepR is expressed in brain, pituitary gland and gonads, but studies using genetically engineered mouse models determined that the brain plays a major role. Recently, it has been made clear that leptin acts indirectly on gonadotropin-releasing hormone (GnRH)-secreting cells via actions on interneurons. However, the exact site(s) of leptin action has been difficult to determine. In this review, we discuss the recent advances in the field focused on the identification of potential site(s) or specific neuronal populations involved in leptin's effects in the neuroendocrine reproductive axis. PMID:21099209

  3. Plasma leptin during reproduction in European Starlings (Sturnus vulgaris)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Leptin, a systemic hormone produced by adipocytes or fat cells, has been widely studied in mammals, and is known to play diverse roles in body mass regulation, immune function, reproduction, etc. However we know very little about avian leptin, especially in free-living birds; indeed, this remains a ...

  4. Anxiolytic-like effects of leptin on fixed interval responding.

    PubMed

    Tyree, Susan M; Munn, Robert G K; McNaughton, Neil

    2016-09-01

    Leptin has been shown to affect energy homeostasis, learning and memory, and some models of anxiolytic action. However, leptin has produced inconsistent results in previous non-operant behavioural tests of anxiety. Here, we test the anxiolytic potential of leptin in an operant paradigm that has produced positive results across all classes of anxiolytic so far tested. Rats were tested in the Fixed Interval 60 Seconds (FI60) task following administration of 0/0.5/1.0mg/kg (i.p.) leptin or an active anxiolytic control of 5mg/kg (i.p.) chlordiazepoxide (CDP). By the end of the 14days of testing in the FI60 task, 0.5mg/kg leptin released suppressed responding in a manner similar to CDP, and 1.0mg/kg leptin produced a relative depression in responding, a similar outcome pattern to previously tested 5HT-agonist anxiolytics. This suggests that leptin behaves similarly to established serotonergic anxiolytics such as buspirone and fluoxetine; with the delay in development of effect during testing, and the inverted-U dose-response curve explaining the inconsistent behaviour of leptin in behavioural tests of anxiety, as this type of pattern is common to serotonergic anxiolytics. PMID:27180106

  5. Development of Dissociation-Enhanced Lanthanide Fluoroimmunoassay for Measuring Leptin.

    PubMed

    Kim, Namsoo; Son, So-Hee

    2016-09-01

    Development of a dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) for measuring leptin, a satiety hormone of appetite control, was conducted in sandwich assay format exploiting a microplate immobilized with an anti-leptin antibody and another antibody raised against leptin and tagged with an europium chelate. In the leptin DELFIA of this study, amounts of antibody coated to the microplate and of the bioconjugate for the second immune reaction were optimized as 0.5 μg and 200 ng per well, respectively. When plotted in double-logarithmic scale, a linear relationship of y (log10 response signal) = 0.6023× (log10 leptin concentration) + 3.4084 (r(2) = 0.9646) was obtained at the leptin concentrations of 0.01─50 ng/mL with the limit of detection of 0.01 ng/mL. Individual leptin concentrations in various samples were well convergent to the calibration curve of the current assay. When applied to the measurement of leptin in a rat serum, the present assay was found quite effective and was competitive to a commercial sandwich-type ELISA. PMID:27343179

  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. PMID:26610729

  7. Effect of repeated US stimulation on adiponectin secretion by adipocytes of obese human subjects

    NASA Astrophysics Data System (ADS)

    Fujii, Yasutomo; Taniguchi, Nobuyuki; Satoh, Masaaki; Irie, Takasuke; Itoh, Kouichi

    2006-05-01

    To clarify the effect of the repeated sonication on the adiponectin secretion by adipocytes obtained from obese subjects. Using 1-MHz continuous-wave ultrasound at an intensity of 0.50 or 2.1 W/cm2, we sonicated culture flasks of subcutaneous adipocytes obtained from obese human subjects, in a series of 3 sessions of US stimulation applied for a daily total of 15 min. For the measurement of adiponectin secretion, 50 μl of the culture medium was collected from each flask every 24 h after the 1st stimulation. Quantification of adiponectin protein levels in cell culture supernatants was performed with a commercially available ELISA kit recommended by the manufacturer. The adiponectin concentrations in the culture medium of the US stimulation groups rose significantly (p<0.05). Repeated US stimulation may accelerate adiponectin secretion in obese human adipocytes.

  8. Adiponectin Regulates Vascular Endothelial Growth Factor-C Expression in Macrophages via Syk-ERK Pathway

    PubMed Central

    Hu, Di; Fukuhara, Atsunori; Miyata, Yugo; Yokoyama, Chieko; Otsuki, Michio; Kihara, Shinji; Shimomura, Iichiro

    2013-01-01

    Adiponectin is exclusively expressed in adipose tissues and exhibits protective effects against cardiovascular and metabolic diseases. It enhances AMP-activated kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα) signaling in the liver and skeletal muscles, however, its signaling pathways in macrophages remain to be elucidated. Here, we show that adiponectin upregulated the expression of vascular endothelial growth factor (VEGF)-C, and induced phosphorylation of extracellular signal-regulated kinase (ERK) in macrophages. Inhibition of Syk abrogated adiponectin-induced VEGF-C expression and ERK phosphorylation. Furthermore, inhibition of ERK blocked the induction of VEGF-C gene. Inhibition of Syk, but not that of ERK, abrogated adiponectin-induced expression of cyclooxygenase (COX)-2, tissue inhibitor of metalloproteinase (TIMP)-1, and interleukin (IL)-6. These results indicate that adiponectin regulates VEGF-C expression via Syk-ERK pathway in macrophages. PMID:23424645

  9. Expression of functional leptin receptors in rodent Leydig cells.

    PubMed

    Caprio, M; Isidori, A M; Carta, A R; Moretti, C; Dufau, M L; Fabbri, A

    1999-11-01

    Several studies indicate that the size of body fat stores and the circulating levels of the adipocyte-derived hormone leptin are able to influence the activity of the hypothalamic-pituitary-gonadal axis. The leptin-hypothalamic-pituitary-gonadal interactions have been mainly studied at the level of the central nervous system. In this study, we investigated the possibility that leptin may have direct effects on the rodent Leydig cell function. To probe this hypothesis, we first analyzed the expression of leptin receptors (OB-R) in rodent Leydig cells in culture. RT-PCR studies showed that rat Leydig cells express both the long (OB-Rb) and short isoform (OB-Ra) of leptin receptor, whereas MLTC-1 cells (a murine Leydig tumor cell line) express only the long isoform. Short-term (30-90 min) incubation of rat Leydig cells with increasing concentrations ofleptin (2-500 ng/ml) led to a significant and dose-dependent inhibition of human (h)CG-stimulated testosterone (T) production (approximately 60% reduction, IC50 = 20 ng/ml) but no change in basal androgen release. Also, leptin (150 ng/ml) amplified hCG-induced intracellular cAMP formation (1- to 2-fold) without modifying basal cAMP levels. Subsequent experiments showed that leptin inhibited 8Br-cAMP-stimulated T production, indicating that leptin's effect is exerted beyond cAMP. The inhibitory effect of leptin on hCG-induced T secretion was accompanied by a significant reduction of androstenedione and a concomitant rise of the precursor metabolites pregnenolone, progesterone, and 17-OH-progesterone, conceivable with a leptin-induced lesion of 17,20 lyase activity. Separate experiments performed with the MLTC-1 cells (not expressing cytochrome P450-17alpha) showed that leptin, though amplifying hCG-stimulated cAMP production, did not modify hCG-stimulated pregnenolone and progesterone release. These results further indicate that leptin action on steroidogenesis occurs downstream of progesterone synthesis. Northern Blot

  10. Lateral Thinking About Leptin: A Review of Leptin Action via the Lateral Hypothalamus

    PubMed Central

    Leinninger, Gina M.

    2011-01-01

    The lateral hypothalamic area (LHA) was initially described as a “feeding center” but we are now beginning to understand that the LHA contributes to other aspects of physiology as well. Indeed, the best-characterized neuronal populations of the LHA (which contain melanin-concentrating hormone (MCH) or the hypocretins/orexins (OX) are not strictly orexigenic, but also have roles in regulation of the autonomic and sympathetic nervous systems as well as in modulating motivated behavior. Leptin is an anorectic hormone that regulates energy homeostasis and the mesolimbic DA system (which transduces the wanting of food, drugs of abuse and sex) in part, via actions at the LHA. At least three populations of LHA neurons are regulated by leptin: those containing MCH, OX or the long form of the leptin receptor, LepRb. The emerging picture of leptin interaction with these LHA populations suggests that the LHA is not merely regulating feeding, but is a crucial integrator of energy balance and motivated behavior. PMID:21550356

  11. Leptin expression affects metabolic rate in zebrafish embryos (D. rerio)

    PubMed Central

    Dalman, Mark R.; Liu, Qin; King, Mason D.; Bagatto, Brian; Londraville, Richard L.

    2013-01-01

    We used antisense morpholino oligonucleotide technology to knockdown leptin-(A) gene expression in developing zebrafish embryos and measured its effects on metabolic rate and cardiovascular function. Using two indicators of metabolic rate, oxygen consumption was significantly lower in leptin morphants early in development [<48 hours post-fertilization (hpf)], while acid production was significantly lower in morphants later in development (>48 hpf). Oxygen utilization rates in <48 hpf embryos and acid production in 72 hpf embryos could be rescued to that of wildtype embryos by recombinant leptin coinjected with antisense morpholino. Leptin is established to influence metabolic rate in mammals, and these data suggest leptin signaling also influences metabolic rate in fishes. PMID:23847542

  12. Creation and Preliminary Characterization of a Leptin Knockout Rat

    PubMed Central

    Vaira, Sergio; Yang, Chang; McCoy, Aaron; Keys, Kelly; Xue, Shurong; Weinstein, Edward J.; Novack, Deborah V.

    2012-01-01

    Leptin, a cytokine-like hormone secreted mainly by adipocytes, regulates various pathways centered on food intake and energy expenditure, including insulin sensitivity, fertility, immune system, and bone metabolism. Here, using zinc finger nuclease technology, we created the first leptin knockout rat. Homozygous leptin null rats are obese with significantly higher serum cholesterol, triglyceride, and insulin levels than wild-type controls. Neither gender produced offspring despite of repeated attempts. The leptin knockout rats also have depressed immune system. In addition, examination by microcomputed tomography of the femurs of the leptin null rats shows a significant increase in both trabecular bone mineral density and bone volume of the femur compared with wild-type littermates. Our model should be useful for many different fields of studies, such as obesity, diabetes, and bone metabolism-related illnesses. PMID:22948215

  13. Evaluation of leptin receptor expression on buffalo leukocytes.

    PubMed

    De Matteis, Giovanna; Grandoni, Francesco; Scatà, Maria Carmela; Catizone, Angela; Reale, Anna; Crisà, Alessandra; Moioli, Bianca

    2016-09-01

    Experimental evidences support a direct role for leptin in immunity. Besides controlling food intake and energy expenditure, leptin was reported to be involved in the regulation of the immune system in ruminants. The aim of this work was to highlight the expression of leptin receptor (LEPR) on Bubalus bubalis immune cells using a multi-approach assessment: flow cytometry, confocal microscopy and gene expression analysis. Flow cytometric analysis of LEPR expression showed that peripheral blood monocytes were the predominant cells expressing LEPR. This result was corroborated by confocal microscopy and RT-PCR analysis. Moreover, among lymphocytes, LEPR was mainly expressed by B lymphocytes and Natural Killer cells. Evidence of LEPR expression on buffalo blood leukocytes showed to be a good indicator of the responsivity of these cells to leptin, so confirming the involvement of leptin in buffalo immune response. PMID:27436440

  14. Circulating Leptin and Pain Perception among Tobacco Dependent Individuals

    PubMed Central

    al’Absi, Mustafa; Lemieux, Andrine; Nakajima, Motohiro; Hatsukami, Dorothy K.; Allen, Sharon

    2015-01-01

    Recent preclinical evidence suggests that leptin may modulate the stress response and may increase nociception. In this study, we examined for the first time the extent to which cigarette smoking is associated with leptin levels during an extended rest period and in response to noxious stimuli. Repeated blood samples were collected during a laboratory session from smokers and nonsmokers and assayed for leptin. Pain experiences, as well as neuroendocrine and cardiovascular measures, were collected across cold pressor and thermal heat pain tests. Both analysis of variance and correlations confirmed that smokers demonstrated dysregulations in leptin responsivity and association with pain relative to nonsmokers. The flat pattern of leptin release and the weak associations of this hormone with pain in smokers suggest a long-term effect of tobacco dependence on this regulatory hormone. In light of leptin’s influence on reward pathways, further investigation of leptin’s involvement in nicotine dependence is warranted. PMID:25720946

  15. 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

    2016-01-01

    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

  16. 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

  17. Site-specific circadian expression of leptin and its receptor in human adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian variability of circulating leptin levels has been well established over the last decade. However, the circadian behavior of leptin in human adipose tissue remains unknown. This also applies to the soluble leptin receptor. We investigated the ex vivo circadian behavior of leptin and its rec...

  18. Meta-Chlorophenylpiperazine enhances leptin sensitivity in diet-induced obese mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most forms of human obesity are characterized by impaired leptin sensitivity and, therefore, the effectiveness of anti-obesity leptin therapy in these leptin-resistant obese patients is marginal. Hence, the development of strategies to increase leptin sensitivity is of high priority in the field of ...

  19. Associations of Candidate SNP on Age, Leptin Concentration, Backfat, and Body Weight at Puberty in Gilts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Body weight (BW), backfat thickness (BF), and leptin play important roles in livestock reproduction. The objective of this study was to determine whether polymorphisms in the leptin (LEP), leptin receptor (LEPR), PAX5, and POMC genes were associated with age, leptin concentration, body condition as ...

  20. Production, gene structure and characterization of two orthologs of leptin and a leptin receptor in tilapia.

    PubMed

    Shpilman, Michal; Hollander-Cohen, Lian; Ventura, Tomer; Gertler, Arieh; Levavi-Sivan, Berta

    2014-10-01

    Full-length cDNA encoding two leptin sequences (tLepA and tLepB) and one leptin receptor sequence (tLepR) were identified in tilapia (Oreochromis niloticus). The full-length cDNA of tLepR was 3423bp, encoding a protein of 1140 amino acid (aa) which contained all functionally important domains conserved among vertebrate leptin receptors. The cDNAs of tLepA and tLepB were 486bp and 459bp in length, encoding proteins of 161 aa and 152 aa, respectively. Modeling the three-dimensional structures of tLepA and tLepB predicted strong conservation of tertiary structure with that of human leptin, comprised of four helixes. Using synteny, the tLeps were found near common genes, such as IMPDH1 and LLRC4. The cDNA for tLepA and tLepB was cloned and synthetic cDNA optimized for expression in Escherichia coli was prepared according to the cloned sequence. The tLepA- and tLepB-expressing plasmids were transformed into E. coli and expressed as recombinant proteins upon induction with nalidixic acid, found almost entirely in insoluble inclusion bodies (IBs). The proteins were solubilized, refolded and purified to homogeneity by anion-exchange chromatography. In the case of tLepA, the fraction eluted contained a mixture of monomers and dimers. The purified tLepA and tLepB monomers and tLepA dimer showed a single band of ∼15kDa on an SDS-polyacrylamide gel in the presence of reducing agent, whereas the tLepA dimer showed one band of ∼30kDa in the absence of reducing agent, indicating its formation by S-S bonds. The three tLeps were biologically active in promoting proliferation of BAF/3 cells stably transfected with the long form of human leptin receptor (hLepR), but their activity was four orders of magnitude lower than that of mammalian leptin. Furthermore, the three tLeps were biologically active in promoting STAT-LUC activation in COS7 cells transfected with the identified tLepR but not in cells transfected with hLepR. tLepA was more active than tLepB. Low or no activity

  1. 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

  2. MicroRNA-378 Regulates Adiponectin Expression in Adipose Tissue: A New Plausible Mechanism

    PubMed Central

    Ishida, Masayoshi; Shimabukuro, Michio; Yagi, Shusuke; Nishimoto, Sachiko; Kozuka, Chisayo; Fukuda, Daiju; Soeki, Takeshi; Masuzaki, Hiroaki; Tsutsui, Masato; Sata, Masataka

    2014-01-01

    Aims Mechanisms regulating adiponectin expression have not been fully clarified. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, are involved in biological processes, including obesity and insulin resistance. We evaluated whether the miRNA-378 pathway is involved in regulating adiponectin expression. Methods and Results First, we determined a putative target site for miRNA-378 in the 3 prime untranslated region (3'UTR) of the adiponectin gene by in silico analysis. The levels of adiponectin mRNA and protein were decreased in 3T3-L1 cells overexpressing the mimic of miRNA-378. Luminescence activity in HEK293T cells expressing a renilla-luciferase-adiponectin-3'UTR sequence was inhibited by overexpressing the mimic of miRNA-378, and the decrease was reversed by adding the inhibitor of miRNA-378. Moreover, we confirmed the inhibitory effects of the mimic were cancelled in a deleted mutant of the miR-378 3′-UTR binding site. Addition of tumor necrosis factor-α (TNFα) led a upregulation of miR-378 and downregulation of adiponectin at mRNA and protein levels in 3T3-L1 cells. Level of miR-378 was higher and mRNA level of adiponectin was lower in diabetic ob/ob mice than those of normal C57BL/6 mice and levels of miR378 and adiponectin were negatively well correlated (r = −0.624, p = 0.004). Conclusions We found that levels of miRNA-378 could modulate adiponectin expression via the 3'UTR sequence-binding site. Our findings warrant further investigations into the role of miRNAs in regulating the adiponectin expression. PMID:25379946

  3. Adiponectin Regulation of Stellate Cell Activation via PPARγ-Dependent and -Independent Mechanisms

    PubMed Central

    Shafiei, Mahnoush S.; Shetty, Shoba; Scherer, Philipp E.; Rockey, Don C.

    2011-01-01

    In this study, we elucidated the mechanism by which adiponectin modulates hepatic stellate cell activation and fibrogenesis. Adiponectin-overexpressing transgenic mice receiving thioacetamide were resistant to fibrosis, compared with controls. In contrast, adiponectin-null animals developed severe fibrosis. Expression of collagen α1(I) and α-smooth muscle actin (α-SMA) mRNAs were significantly lower in adiponectin-overexpressing mice, compared with controls. In wild-type stellate cells exposed to a lentivirus encoding adiponectin, expression of peroxisome proliferator-activated receptor-γ (PPARγ), SREBP1c, and CEBPα mRNAs was significantly increased (3.2-, 4.1-, and 2.2-fold, respectively; n = 3; P < 0.05, adiponectin virus versus control), consistent with possible activation of an adipogenic transcriptional program. Troglitazone, a PPARγ agonist, strongly suppressed up-regulation of collagen α1(I) and α-SMA mRNA in stellate cells isolated from wild-type mice; however, stellate cells from adiponectin-null animals failed to respond to troglitazone. Furthermore, in isolated stellate cells in which PPARγ was depleted using an adenovirus-Cre-recombinase system and in which adiponectin was also overexpressed, collagen α1(I) and α-SMA were significantly inhibited. We conclude that the PPARγ effect on stellate cell activation and the fibrogenic cascade appears to be adiponectin-dependent; however, the inhibitory effect of adiponectin on stellate cell activation was not dependent on PPARγ, suggesting the presence of PPARγ-dependent as well as independent pathways in stellate cells. PMID:21641391

  4. 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

  5. Vascular smooth muscle-specific deletion of the leptin receptor attenuates leptin-induced alterations in vascular relaxation.

    PubMed

    Ryan, Michael J; Coleman, T Taylor; Sasser, Jennifer M; Pittman, Katarina M; Hankins, Michael W; Stec, David E

    2016-05-15

    Obesity is a risk factor for cardiovascular disease and is associated with increased plasma levels of the adipose-derived hormone leptin. Vascular smooth muscle cells (VSMC) express leptin receptors (LepR); however, their physiological role is unclear. We hypothesized that leptin, at levels to mimic morbid obesity, impairs vascular relaxation. To test this, we used control and VSM-LepR knockout mice (VSM-LepR KO) created with a tamoxifen-inducible specific Cre recombinase to delete the LepR gene in VSMC. Control (10-12 wk old) and VSM-LepR KO (10-12 wk old) mice were fed a diet containing tamoxifen (50 mg/kg) for 6 wk, after which vascular reactivity was studied in isolated carotid arteries using an organ chamber bath. Vessels were incubated with leptin (100 ng/ml) or vehicle (0.1 mM Tris·HCl) for 30 min. Leptin treatment resulted in significant impairment of vessel relaxation to the endothelial-specific agonist acetylcholine (ACh). When these experiments were repeated in the presence of the superoxide scavenger tempol, relaxation responses to ACh were restored. VSM-LepR deletion resulted in a significant attenuation of leptin-mediated impaired ACh-induced relaxation. These data show that leptin directly impairs vascular relaxation via a VSM-LepR-mediated mechanism, suggesting a potential pathogenic role for leptin to increase cardiovascular risk during obesity. PMID:26936780

  6. Serum leptin concentrations, leptin mRNA expression, and food intake during the estrous cycle in rats.

    PubMed

    Fungfuang, Wirasak; Nakada, Tomoaki; Nakao, Nobuhiro; Terada, Misao; Yokosuka, Makoto; Gizurarson, Sveinbjorn; Hau, Jann; Moon, Changjong; Saito, Toru R

    2013-03-01

    The aim of this study was to investigate food intake, serum leptin levels, and leptin mRNA expression during the sexual cycle in rats. Female Wistar-Imamichi rats aged 8-10 weeks were used in this experiment. Food intake was measured during the light and dark phases (light on at 07:00 and off at 19:00) of the 4-day estrous cycle in female rats. Serum leptin levels were measured by ELISA, and leptin mRNA expression levels were analyzed using real-time PCR on diestrous- and proestrous-stage rats. Our results revealed that during the sexual cycle, food intake was significantly higher in the dark phase compared with the light phase. Food intake in proestrous females was significantly lower in the light and dark phases compared with the other groups. Serum leptin concentrations were significantly higher in both phases in proestrous rats compared with diestrous rats. There was a significant increase in leptin mRNA expression in adipose tissue during the proestrous period compared with the diestrous period. These findings suggest that increased leptin mRNA expression and serum leptin levels, which are induced by estrogen during the proestrous stage, may play a role in regulating appetitive behavior. PMID:23573101

  7. Leptin suppresses sweet taste responses of enteroendocrine STC-1 cells.

    PubMed

    Jyotaki, Masafumi; Sanematsu, Keisuke; Shigemura, Noriatsu; Yoshida, Ryusuke; Ninomiya, Yuzo

    2016-09-22

    Leptin is an important hormone that regulates food intake and energy homeostasis by acting on central and peripheral targets. In the gustatory system, leptin is known to selectively suppress sweet responses by inhibiting the activation of sweet sensitive taste cells. Sweet taste receptor (T1R2+T1R3) is also expressed in gut enteroendocrine cells and contributes to nutrient sensing, hormone release and glucose absorption. Because of the similarities in expression patterns between enteroendocrine and taste receptor cells, we hypothesized that they may also share similar mechanisms used to modify/regulate the sweet responsiveness of these cells by leptin. Here, we used mouse enteroendocrine cell line STC-1 and examined potential effect of leptin on Ca(2+) responses of STC-1 cells to various taste compounds. Ca(2+) responses to sweet compounds in STC-1 cells were suppressed by a rodent T1R3 inhibitor gurmarin, suggesting the involvement of T1R3-dependent receptors in detection of sweet compounds. Responses to sweet substances were suppressed by ⩾1ng/ml leptin without affecting responses to bitter, umami and salty compounds. This effect was inhibited by a leptin antagonist (mutant L39A/D40A/F41A) and by ATP gated K(+) (KATP) channel closer glibenclamide, suggesting that leptin affects sweet taste responses of enteroendocrine cells via activation of leptin receptor and KATP channel expressed in these cells. Moreover, leptin selectively inhibited sweet-induced but not bitter-induced glucagon-like peptide-1 (GLP-1) secretion from STC-1 cells. These results suggest that leptin modulates sweet taste responses of enteroendocrine cells to regulate nutrient sensing, hormone release and glucose absorption in the gut. PMID:27353597

  8. CONTROL OF BLOOD PRESSURE, APPETITE AND GLUCOSE BY LEPTIN IN MICE LACKING LEPTIN RECEPTORS IN POMC NEURONS

    PubMed Central

    do Carmo, Jussara M.; da Silva, Alexandre A.; Cai, Zhengwei; Lin, Shuying; Dubinion, John H.; Hall, John E.

    2011-01-01

    Although the CNS melanocortin system is an important regulator of energy balance, the role of proopiomelanocortin (POMC) neurons in mediating the chronic effects of leptin on appetite, blood pressure, and glucose regulation is unknown. Using Cre/loxP technology we tested whether leptin receptor deletion in POMC neurons (LepRflox/flox/POMC-Cre mice) attenuates the chronic effects of leptin to increase mean arterial pressure (MAP), enhance glucose utilization and oxygen consumption (VO2), and reduce appetite. LepRflox/flox/POMC-Cre, wild-type (WT), LepRflox/flox and POMC-Cre mice were instrumented for MAP and heart rate (HR) measurement by telemetry, and venous catheters for infusions. LepRflox/flox/POMC-Cre mice were heavier, hyperglycemic, hyperinsulinemic, and hyperleptinemic compared to WT, LepRflox/flox and POMC-Cre mice. Despite exhibiting features of metabolic syndrome, LepRflox/flox/POMC-Cre mice had normal MAP and HR compared to LepRflox/flox but lower MAP and HR compared to WT mice. After a 5-day control period, leptin was infused (2 μg/kg/min, i.v.) for 7 days. In control mice, leptin increased MAP by ~5 mmHg despite decreasing food intake by ~35%. In contrast, leptin infusion in LepRflox/flox/POMC-Cre mice reduced MAP by ~3 mmHg and food intake by ~28%. Leptin significantly decreased insulin and glucose levels in control mice but not in LepRflox/flox/POMC-Cre mice. Leptin increased VO2 in LepRflox/flox/POMC-Cre and WT mice. Activation of POMC neurons is necessary for the chronic effects of leptin to raise MAP and reduce insulin and glucose levels, whereas leptin receptors in other areas of the brain besides POMC neurons appear to play a key role in mediating leptin’s chronic effects on appetite and VO2. PMID:21422382

  9. Leptin inhibits steroid biosynthesis by human granulosa-lutein cells.

    PubMed

    Ghizzoni, L; Barreca, A; Mastorakos, G; Furlini, M; Vottero, A; Ferrari, B; Chrousos, G P; Bernasconi, S

    2001-06-01

    Absence of leptin secretion compromises reproductive function and fertility in t