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Adiponectin
Kinds of Adiponectin Terms modified by Adiponectin Selected AbstractsThe effect of thiazolidinediones on adiponectin serum level: a meta-analysisDIABETES OBESITY & METABOLISM, Issue 5 2008N. Riera-Guardia Background and aims:, Adiponectin is a hormone mainly produced by white adipose tissue. Decreased levels of adiponectin are linked with visceral obesity, insulin resistance states, and cardiovascular diseases. Recently, several studies have pointed out an increase in adiponectin serum levels in subjects undergoing treatment with thiazolidinediones (TZD). The aim of this study is to systematically review the current state of evidence of the effect of TZD on adiponectin serum level with special attention to avoid publication bias. Materials and methods:, An extensive literature search was performed. Meta Analysis Version 2.0 computer program was used to calculate statistical differences in means and 95% confidence interval (CI). Publication bias was assessed using different statistical approaches. Results:, In the meta-analysis including 19 studies the overall standardized mean difference was 0.94 (95% CI, 0.81,1.06) which means that subjects treated with TZDs on average had means of adiponectin concentration that were about 1 standard deviation higher than the comparison groups even after controlling for possible biases. Conclusions:, The results obtained agree with a moderate increase of serum adiponectin. The results clearly reveal an increase of endogenous serum adiponectin levels by intake of TZDs and may point to a potential new option to manage obesity-related diseases. [source] Adiponectin and visfatin concentrations in children treated with valproic acidEPILEPSIA, Issue 2 2008Markus Rauchenzauner Summary Chronic antiepileptic therapy with valproic acid (VPA) is associated with increased body weight and insulin resistance in adults and children. Attempts to determine the underlying pathophysiologic mechanisms have failed. Adipocytokines have recently been defined as a link between glucose and fat metabolism. We herein demonstrate that VPA-associated overweight is accompanied by lower adiponectin and higher leptin concentrations in children. The absence of any relationship with visfatin concentration does not suggest a role of this novel insulin-mimetic hormone in VPA-associated metabolic alterations. Therefore, adiponectin and leptin but not visfatin may be considered as potential regulators of glucose and fat metabolism during VPA-therapy. [source] Adiponectin protects LPS-induced liver injury through modulation of TNF-, in KK-Ay obese miceHEPATOLOGY, Issue 1 2004Takayuki Masaki Adiponectin, an adipocytokine, has been identified in adipose tissue, and its receptors are widely distributed in many tissues, including the liver. The present study was performed to clarify the role of adiponectin in lipopolysaccharide (LPS)-induced liver injury using KK-Ay obese mice. We analyzed the effects of adiponectin pretreatment on liver injury induced by D -galactosamine/LPS (GalN/LPS) in KK-Ay obese mice. GalN/LPS treatment induced significant increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the blood, apoptotic and necrotic changes in hepatocytes, and/or showed a high degree of lethality. The GalN/LPS-induced liver injury was more pronounced in KK-Ay obese mice than in lean controls. Pretreatment with adiponectin ameliorated the GalN/LPS-induced elevation of serum AST and ALT levels and the apoptotic and necrotic changes in hepatocytes, resulting in a reduction in lethality. In addition, pretreatment with adiponectin attenuated the GalN/LPS-induced increases in serum and hepatic tumor necrosis factor , (TNF-,) levels and increased peroxisome proliferator-activated receptor (PPAR) , messenger RNA expression in the liver. Furthermore, abdominal macrophages from KK-Ay obese mice pretreated with adiponectin in vitro exhibited decreased LPS-induced TNF-, production compared with controls. Finally, adiponectin pretreatment also ameliorated TNF-,-induced liver injury. In conclusion, these findings suggest that adiponectin prevents LPS-induced hepatic injury by inhibiting the synthesis and/or release of TNF-, of KK-Ay obese mice. (HEPATOLOGY 2004;40:177,184.) [source] Adiponectin as a therapeutic target of non-alcoholic steatohepatitisHEPATOLOGY RESEARCH, Issue 10 2009Goshi Shiota No abstract is available for this article. [source] Regulation of adiponectin in adipocytes upon exposure to HIV-1HIV MEDICINE, Issue 4 2006J-LG Sankalé Objectives 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 peptide implicated in regulation of glucose and lipid metabolisms. In this study we investigated the effect of HIV on adipocytes, to determine whether HIV can directly infect adipocytes and/or alter the regulation and secretion of the adipocyte-derived hormone adiponectin. Methods Human subcutaneous preadipocytes and adipocytes were exposed to HIV-1 under various conditions. Adiponectin was measured in supernatants and cell lysates. Results Although adipocytes expressed CD4, the major HIV receptor, they could not be infected in vitro. However, exposure to HIV dramatically increased the secretion of adiponectin from human adipocytes, in the absence of infection. This was exacerbated with sustained exposure to HIV in a transwell assay. Further, human peripheral mononuclear cells also produced adiponectin, but this was largely dependent upon T-cell activation. Conclusions We propose that the stimulation of adiponectin production by HIV can perturb adiponectin regulation, leading to substantially decreased levels upon viral suppression by antiretroviral therapy. These data suggest a potential molecular mechanism of adiponectin regulation in HIV-infected patients. [source] Low adiponectin levels are associated with renal cell carcinoma: A case-control studyINTERNATIONAL JOURNAL OF CANCER, Issue 7 2007Themistoklis N. Spyridopoulos Abstract Adiponectin is a novel endogenous insulin sensitizer, secreted by mature adipocytes. Circulating levels of adiponectin are inversely associated with obesity and insulin resistance. Because obesity is a risk factor for renal cell carcinoma (RCC), we hypothesized that low adiponectin levels are associated with RCC. To evaluate this hypothesis, we conducted a case- control study of 70 patients with histologically confirmed RCC and 280 healthy controls matched by gender, age and county of residence. Study subjects were interviewed and blood samples were collected during a 32-month period in Athens, Greece. Serum adiponectin levels were statistically, significantly and inversely associated with RCC when compared with controls (OR = 0.76, p = 0.05) and this association remained practically unchanged after controlling for BMI; the introduction of waist to hip ratio along with adiponectin in the multiple logistic regression analysis model rendered the association between adiponectin and RCC risk insignificant, indicating that altered levels of adiponectin may mediate the effect of central or intra-abdominal obesity on RCC. Prospective studies as well as studies exploring underlying mechanisms are needed to fully explore the role of adiponectin in predicting future risk of RCC in humans. © 2006 Wiley-Liss, Inc. [source] Involvement of the JAK-STAT pathway and SOCS3 in the regulation of adiponectin-generated reactive oxygen species in murine macrophage RAW 264 cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2010Sumio Akifusa Abstract Adiponectin is a protein hormone produced by differentiating adipocytes and has been proposed to have anti-diabetic and immunosuppressive properties. We previously reported that the globular form of adiponectin (gAd) induces the generation of reactive oxygen species (ROS) and nitric oxide (NO), followed by caspase-dependent apoptotic cell death in RAW 264 cells. Here, we demonstrate that gAd-induced ROS generation and apoptosis were diminished by suppressor of cytokine signaling 3 (SOCS3). The phosphorylation level of signal transducer and activator of transcription (STAT) 3 detected by Western blotting was highest at 20,min in gAd-treated RAW 264 cells. This phosphorylation was inhibited by AG490, a specific inhibitor of janus-activator kinase (JAK). The gAd-induced ROS and NO were reduced by administration of AG490 and Jak-2-specific siRNA in RAW 264 cells. The gAd stimulation transiently induced SOCS3 mRNA expression and protein production. We examined SOCS3-overexpressing RAW 264 cells to investigate the role of the JAK-STAT pathway in gAd-induced ROS and NO generation. SOCS3 overexpression significantly reduced both ROS and NO generation. Additionally, gAd-induced caspase activation and apoptotic cell death were reduced in SOCS3 transfectants compared with vector control transfectants. These results suggest that the JAK-STAT pathway, which can be suppressed by SOCS3 expression, is involved in gAd-induced ROS and NO generation followed by apoptotic cell death. J. Cell. Biochem. 111: 597,606, 2010. © 2010 Wiley-Liss, Inc. [source] Adiponectin Is a Link Among Inflammation, Insulin Resistance, and High-Density Lipoprotein Cholesterol But Is Not Associated With Paraoxonase Activity in Premenopausal WomenJOURNAL OF CLINICAL HYPERTENSION, Issue 11 2009Pinar Cetinalp-Demircan PhD The aim of this study was to evaluate whether insulin sensitivity, inflammatory response, and plasma lipid profile are associated with circulating adiponectin levels in nondiabetic healthy women. The authors also assessed whether adiponectin has any effect on high-density lipoprotein cholesterol,linked paraoxonase 1 (PON-1) activity and on the susceptibility of low-density lipoproteins to oxidation. Plasma adiponectin was measured in 91 nondiabetic premenopausal women, and the patients were then divided into quartiles. Circulating adiponectin was found to be associated with body mass index (r=.55, P<.001). After adjustment for body mass index, adiponectin showed an inverse correlation with the homeostasis model assessment of insulin resistance (HOMA-IR) (r=,.41, P<.001) and a positive correlation with high-density lipoprotein cholesterol (r=.43, P<.001). In linear regression analysis, HOMA-IR, tumor necrosis factor ,, and high-density lipoprotein cholesterol levels were found to be independently associated with adiponectin. However, high-density lipoprotein cholesterol,linked PON-1 activity and the susceptibility of low-density lipoproteins to in vitro oxidation did not seem to be related to plasma adiponectin concentrations. [source] Expression of adiponectin and its receptors in livers of morbidly obese patients with non-alcoholic fatty liver diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2009Hong Ma Abstract Background and Aim:, Obesity is one of the risk factors for non-alcoholic fatty liver disease (NAFLD) and a common disease that comprises simple steatosis and non-alcoholic steatohepatitis (NASH), and can eventually lead to liver cirrhosis. Adiponectin is an adipocyte-derived protein that has anti-obesity, antidiabetic and anti-inflammatory properties, and is considered to possess a hepatoprotective function. Its role in the development and progression of NAFLD in morbidly obese patients is unknown. In this study, we examined the expression levels of adiponectin and its receptors in liver biopsies of morbidly obese patients and then determined whether there was an association with the disease severity. Methods:, Liver biopsies from 30 morbidly obese patients (18 NASH vs 12 steatosis) were analyzed. The needle core biopsies were subjected to routine histological examination and stained immunohistochemically for adiponectin, adiponectin receptor I (adipoRI) and receptor II (adipoRII). Results:, The two groups were comparable with respect to body mass index, age and gender distribution. The expression of adiponectin decreased in liver biopsies with NASH as compared to those with simple steatosis (1.61 ± 0.70 vs 2.25 ± 0.75, P = 0.028). Spearman's rank correlation coefficient analysis showed that the staining intensity of adiponectin negatively correlated with the grade of inflammation (r = ,0.368, P = 0.045) and stage of fibrosis (r = ,0.380, P = 0.038). There was no significant difference in expression of adipoRI and adipoRII between the two groups. Conclusion:, These findings indicate that decreased liver adiponectin expression may play a role in the development and progression of NAFLD, from simple steatosis to NASH, in morbidly obese patients. [source] Relationship of adiponectin and resistin levels in umbilical and maternal serum with fetal macrosomiaJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2010Jing Wang Abstract Aim:, Adiponectin and resistin are novel hormones secreted by human adipocytes and mononuclear cells, which have been postulated to play roles in the regulation of energy metabolism during pregnancy. However, correlations between adiponectin and resistin levels in umbilical and maternal serum and fetal macrosomia remain poorly understood. The purpose of this study was to clarify the relationship of adiponectin and resistin levels in umbilical and maternal serum with fetal macrosomia. Methods:, Serum adiponectin and resistin levels were prospectively measured by enzyme immunoassay in 70 mothers and their 70 neonates. The study group included 30 neonates with macrosomia and the control group included 40 neonates that were appropriate for gestational age. The correlations of cord serum adiponectin and resistin with maternal serum adiponectin and resistin, birth weight, body mass index (BMI), and placental weight were analyzed. Results:, Serum adiponectin and resistin levels were significantly decreased in macrosomic mothers compared with those in control women. The levels of adiponectin and resistin were diminished in macrosomic babies in comparison with control newborns. Umbilical serum adiponectin levels were inversely correlated with birth weight, newborn BMI, and placental weight, but not with maternal serum adiponectin levels. Umbilical serum resistin levels had a positive correlation with maternal serum resistin and a negative correlation with birth weight, newborn BMI, and placental weight. In addition, maternal serum resistin levels were inversely correlated with newborn birth weight. Conclusion:, It is suggested that adiponectin and resistin play important roles in controlling body weight and may be related to the occurrence of fetal macrosomia. [source] Molecular Mechanisms of Alcoholic Fatty LiverALCOHOLISM, Issue 2 2009Vishnudutt Purohit Alcoholic fatty liver is a potentially pathologic condition which can progress to steatohepatitis, fibrosis, and cirrhosis if alcohol consumption is continued. Alcohol exposure may induce fatty liver by increasing NADH/NAD+ ratio, increasing sterol regulatory element-binding protein-1 (SREBP-1) activity, decreasing peroxisome proliferator-activated receptor-, (PPAR-,) activity, and increasing complement C3 hepatic levels. Alcohol may increase SREBP-1 activity by decreasing the activities of AMP-activated protein kinase and sirtuin-1. Tumor necrosis factor-, (TNF-,) produced in response to alcohol exposure may cause fatty liver by up-regulating SREBP-1 activity, whereas betaine and pioglitazone may attenuate fatty liver by down-regulating SREBP-1 activity. PPAR-, agonists have potentials to attenuate alcoholic fatty liver. Adiponectin and interleukin-6 may attenuate alcoholic fatty liver by up-regulating PPAR-, and insulin signaling pathways while down-regulating SREBP-1 activity and suppressing TNF-, production. Recent studies show that paracrine activation of hepatic cannabinoid receptor 1 by hepatic stellate cell-derived endocannabinoids also contributes to the development of alcoholic fatty liver. Furthermore, oxidative modifications and inactivation of the enzymes involved in the mitochondrial and/or peroxisomal ,-oxidation of fatty acids could contribute to fat accumulation in the liver. [source] Pioglitazone in the treatment of NASH: the role of adiponectinALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010A. Gastaldelli Summary Background, Plasma adiponectin is decreased in NASH patients and the mechanism(s) for histological improvement during thiazolidinedione treatment remain(s) poorly understood. Aim, To evaluate the relationship between changes in plasma adiponectin following pioglitazone treatment and metabolic/histological improvement. Methods, We measured in 47 NASH patients and 20 controls: (i) fasting glucose, insulin, FFA and adiponectin concentrations; (ii) hepatic fat content by magnetic resonance spectroscopy; and (iii) peripheral/hepatic insulin sensitivity (by double-tracer oral glucose tolerance test). Patients were then treated with pioglitazone (45 mg/day) or placebo and all measurements were repeated after 6 months. Results, Patients with NASH had decreased plasma adiponectin levels independent of the presence of obesity. Pioglitazone increased 2.3-fold plasma adiponectin and improved insulin resistance, glucose tolerance and glucose clearance, steatosis and necroinflammation (all P < 0.01,0.001 vs. placebo). In the pioglitazone group, plasma adiponectin was significantly associated (r = 0.52, P = 0.0001) with hepatic insulin sensitivity and with the change in both variables (r = 0.44, P = 0.03). Increase in adiponectin concentration was related also to histological improvement, in particular, to hepatic steatosis (r = ,0.46, P = 0006) and necroinflammation (r = ,0.56, P < 0.0001) but importantly also to fibrosis (r = ,0.29, P = 0.03). Conclusions, Adiponectin exerts an important metabolic role at the level of the liver, and its increase during pioglitazone treatment is critical to reverse insulin resistance and improve liver histology in NASH patients. [source] Total and high molecular weight adiponectin concentrations in plasma of patients with end-stage renal disease before and after peritoneal dialysisNEPHROLOGY, Issue 3 2008JAE-HO PARK SUMMARY: Background: Adiponectin is an antiatherogenic adipocyte-derived proteins. The level of plasma adiponectin is inversely correlated to cardiovascular risk in patients with end-stage renal disease (ESRD). The aim of this study was to elucidate the changes of adiponectin concentrations in newly diagnosed ESRD patients after peritoneal dialysis. Methods: In 16 newly diagnosed ESRD patients, total concentrations of adiponectin and high molecular weight (HMW) adiponectin, the HMW ratio (HMWR; ratio of the plasma level of HMW adiponectin to that of total adiponectin), the body mass index (BMI), insulin concentrations, blood glucose and estimation of the insulin sensitivity index by the homeostasis model assessment (HOMRIR) were compared before and after 1 year of peritoneal dialysis. Results: Plasma total adiponectin was decreased from 15.52 ± 9.35 ,g/mL to 11.80 ± 6.84 ,g/mL (P = 0.046), HMW adiponectin was decreased from 9.05 ± 6.48 ,g/mL to 4.83 ± 4.15 ,g/mL (P = 0.009), and HMWR was decreased from 0.51 ± 0.18 to 0.35 ± 0.20 (P = 0.008). Total and HMW adiponectin/BMI ratio was decreased. The BMI was increased from 25.2 ± 5.7 to 25.8 ± 6.2 (P = 0.036). The HOMRIR, insulin level and lipid profile were not changed. Conclusion: Total adiponectin, HMW adiponectin and HMWR were decreased in newly diagnosed ESRD patients after 1 year of peritoneal dialysis. The factors that influence the decrease of the level of adiponectin should be studied in a larger prospective study. [source] Relationship between adipokines and manifestations of childhood asthmaPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 6 2008Kyung W. Kim Although the prevalences of asthma and obesity are increasing substantially in recent decades, very little is known about the possible association between them. We evaluated the roles of leptin, adiponectin, and resistin, which are adipokines produced by adipose tissue, on childhood asthma, and their association with pulmonary function and bronchial hyperresponsiveness. We studied 149 atopic asthmatic children, 37 non-atopic asthmatic children, and 54 healthy children. Body mass index was calculated using height and weight, which were measured on the same day that pulmonary function tests and methacholine challenge tests were performed. Skin prick tests were performed, and total eosinophil count, total serum immunoglobulin E (IgE), serum eosinophil cationic protein, leptin, adiponectin, and resistin were measured in all subjects. Atopic asthmatics had lower resistin levels compared with non-atopic asthma and control groups, but leptin and adiponectin did not show any difference among these three groups. Resistin demonstrated positive correlation with methacholine PC20 and negative correlations with eosinophil count and serum total IgE. Leptin and adiponectin showed associations with forced expiratory volume in 1 s or forced expiratory flow between 25,75%. Multiple regression analysis revealed that resistin was a significant predictive factor for asthma. There was no direct association between asthma and leptin or adiponectin. Our findings suggest that resistin may play a negative predictive role in asthma. Adiponectin and leptin showed close associations with pulmonary function and may have disease-modifying effects in children with asthma. [source] Adiponectin and type 2 diabetes in Samoan adultsAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 3 2009Julia R. Dibello Objective: Previous studies have established an association between adiponectin and type 2 diabetes. It is unclear whether adiponectin will be useful among Samoan Islanders, characterized by markedly elevated levels of obesity, in differentiating those at risk of developing type 2 diabetes. Methods: Cross-sectional, genetic epidemiology study of obesity in American Samoa and Samoa 2002,2003 (n = 1,599). Logistic regression provided adjusted odds ratios and 95% confidence intervals for the association between adiponectin, diabetes, and prediabetes (impaired fasting glucose). Results: There is a significant decreasing trend in the odds of diabetes and prediabetes across increasing quintiles of adiponectin with an OR of 2.8 (95% CI: 1.6, 5.0) and 2.9 (95% CI: 1.5, 5.7), respectively, in the lowest relative to the highest quintile of adiponectin (P -for-trend = 0.004 and 0.001). Conclusions: Adiponectin is an important correlate, independent of other risk factors, of the pathogenesis of type 2 diabetes among Samoan islanders and may help distinguish those at higher risk of developing this disease. Am. J. Hum. Biol. 2009. © 2008 Wiley-Liss, Inc. [source] Adiponectin-mediated changes in effector cells involved in the pathophysiology of rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 10 2010Klaus W. Frommer Objective Rheumatoid arthritis (RA) is associated with increased production of adipokines, which are cytokine-like mediators that are produced mainly in adipose tissue but also in synovial cells. Since RA synovial fibroblasts (RASFs), lymphocytes, endothelial cells, and chondrocytes are key players in the pathophysiology of RA, this study was undertaken to analyze the effects of the key adipokine adiponectin on proinflammatory and prodestructive synovial effector cells. Methods Lymphocytes were activated in part prior to stimulation. All cells were stimulated with adiponectin, and changes in gene and protein expression were determined by Affymetrix and protein arrays. Messenger RNA and protein levels were confirmed using semiquantitative reverse transcription,polymerase chain reaction (PCR), real-time PCR, and immunoassays. Intracellular signal transduction was evaluated using chemical signaling inhibitors. Results Adiponectin stimulation of human RASFs predominantly induced the secretion of chemokines, as well as proinflammatory cytokines, prostaglandin synthases, growth factors, and factors of bone metabolism and matrix remodeling. Lymphocytes, endothelial cells, and chondrocytes responded to adiponectin stimulation with enhanced synthesis of cytokines and various chemokines. Additionally, chondrocytes released increased amounts of matrix metalloproteinases. In RASFs, adiponectin-mediated effects were p38 MAPK and protein kinase C dependent. Conclusion Our previous findings indicated that adiponectin was present in inflamed synovium, at sites of cartilage invasion, in lymphocyte infiltrates, and in perivascular areas. The findings of the present study indicate that adiponectin induces gene expression and protein synthesis in human RASFs, lymphocytes, endothelial cells, and chondrocytes, supporting the concept of adiponectin being involved in the pathophysiologic modulation of RA effector cells. Adiponectin promotes inflammation through cytokine synthesis, attraction of inflammatory cells to the synovium, and recruitment of prodestructive cells via chemokines, thus promoting matrix destruction at sites of cartilage invasion. [source] Adiponectin stimulates prostaglandin E2 production in rheumatoid arthritis synovial fibroblastsARTHRITIS & RHEUMATISM, Issue 6 2010Natsuko Kusunoki Objective Adipokines may influence inflammatory and/or immune responses. This study was undertaken to examine whether adiponectin affects the production of prostaglandin E2 (PGE2) by rheumatoid arthritis synovial fibroblasts (RASFs). Methods Synovial tissue was obtained from patients with RA who were undergoing joint replacement surgery. Fibroblast-like cells from the third or fourth passage were used as RASFs. Expression of adiponectin receptor messenger RNA (mRNA) and protein was detected. PGE2 (converted from arachidonic acid) was measured by enzyme-linked immunosorbent assay (ELISA). Expression of mRNA and protein for cyclooxygenase 2 (COX-2) and membrane-associated PGE synthase 1 (mPGES-1), key enzymes involved in PGE2 synthesis, was detected in RASFs. The effects of RNA interference (RNAi) targeting the adiponectin receptor genes and the receptor signal inhibitors were examined. The influence of adiponectin on NF-,B activation in RASFs was measured with an ELISA kit. Results Adiponectin receptors were detected in RASFs. Adiponectin increased both COX-2 and mPGES-1 mRNA and protein expression by RASFs in a time- and concentration-dependent manner. PGE2 production by RASFs was also increased by the addition of adiponectin, and this increase was inhibited by RNAi for the adiponectin receptor gene, or coincubation with the receptor signal inhibitors. Enhancement of NF-,B activation by adiponectin as well as by interleukin-1, was observed in RASFs. Conclusion Our findings indicate that adiponectin induces COX-2 and mPGES-1 expression, resulting in the enhancement of PGE2 production by RASFs. Thus, adiponectin may play a role in the pathogenesis of synovitis in RA patients. [source] Activation of AMP-activated protein kinase by adiponectin rescues salivary gland epithelial cells from spontaneous and interferon-,,induced apoptosisARTHRITIS & RHEUMATISM, Issue 2 2010Stergios Katsiougiannis Objective Primary Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltrates associated with destruction of salivary gland epithelial cells (SGECs) induced mainly by apoptosis. Adiponectin is an immunoregulatory hormone. We have previously shown that SGECs from patients with primary SS as well as from controls differentially express adiponectin. SGECs derived from patients with primary SS constitutively produce and secrete adiponectin in higher quantities. The aim of this study was to investigate the effect of adiponectin on the proliferation and apoptosis of SGECs. Methods Cultured, non-neoplastic SGECs were treated with recombinant human adiponectin, and the rate of cell proliferation was assessed. Spontaneous and interferon-, (IFN,),induced apoptosis was evaluated with a specific single-stranded DNA enzyme-linked immunosorbent assay. The AMP-activated protein kinase (AMPK) inhibitor Compound C was used to test the involvement of AMPK in adiponectin effects. Western blotting was applied to detect the phosphorylation levels of AMPK after adiponectin treatment. Results Adiponectin treatment resulted in a dose-dependent suppression of proliferation of SGECs from patients with primary SS and control donors. Adiponectin protected cells from spontaneous as well as from IFN,-induced apoptosis. Furthermore, the antiapoptotic effects of adiponectin were dependent upon AMPK phosphorylation at Thr172, since pretreatment of SGECs with Compound C abolished the adiponectin protective effect. Conclusion Adiponectin exerted antiproliferative effects on SGECs without inducing apoptosis and protected SGECs from spontaneous as well as from IFN,-induced apoptosis through an AMPK-dependent pathway. Our observations suggest that adiponectin may protect SGECs in this specific inflammatory milieu, providing a potential pathway through which AMPK may regulate cell survival under energy stress conditions such as autoimmune inflammation. [source] Proinflammatory Cytokines, Hepatocyte Growth Factor and Adipokines in Peritoneal Dialysis PatientsARTIFICIAL ORGANS, Issue 7 2010Chien-Te Lee Abstract Chronic inflammation is a well-recognized complication in dialysis patients and a potential role of the adipose tissue as an important tissue of origin contributing to inflammation has been proposed. Stable peritoneal dialysis (PD) patients were enrolled to investigate the relationship between serum levels of proinflammatory cytokines and adipokines. Our results revealed that there was a strong association between high sensitivity C-reactive protein and interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-,) but not with IL-10 and IL-18. IL-6 correlated with TNF-,, IL-10, and IL-18. No association was found between IL-10 and IL-18. Adiponectin was positively correlated with all proinflammatory cytokines, except IL-10. No significant association was found between resistin and proinflammatory cytokines. Hepatocyte growth factor (HGF) was directly related to proinflammatory cytokines but not with adipokines. The presence of residual kidney function (RKF) affected IL-6, TNF-,, and HGF levels. The peritoneal transport property did not influence inflammatory cytokine and adipokine levels. In conclusion, there was a close relationship between proinflammatory cytokines and adipokines. HGF correlated with proinflammatory cytokines but not with adipokines. The PD-related factors such as RKF, peritoneal property and dialysis glucose load affected levels of proinflammatory cytokines. Body mass index was an important determinant of leptin and adiponectin in PD patients. [source] Effect of adiponectin on apoptosis: Proapoptosis or antiapoptosis?BIOFACTORS, Issue 3 2010Yiyi Sun Abstract Adiponectin is a protein hormone mainly secreted by adipose tissue that regulates energy homeostasis and glucose and lipid metabolism. Compared with other adipose-derived hormones, adiponectin is very abundant in plasma and is proposed to be a convenient biomarker for many diseases. A large number of in vitro and in vivo studies support the beneficial effects of adiponectin on metabolic syndrome, diabetes, and atherosclerosis. However, the protective actions were challenged occasionally by the controversies in its role in inflammation and in the specific functions of its different conformations. Recently, quite a few reports suggested that the antiapoptotic activity of adiponectin might contribute to its therapeutic potential during ischemia/reperfusion injury in vivo, whereas some studies demonstrated that adiponectin induced apoptosis both in vitro and in vivo. Herein, this review attempts to summarize the present consensus and divergence and to provide possible alternative and/or complementary explanations for this apparent paradox. [source] Short communication: A longitudinal study of serum adiponectin during normal pregnancyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 1 2006Jens Fuglsang Adiponectin is secreted from adipose tissue. Serum adiponectin levels are inversely correlated with body mass index (BMI) and also insulin resistance, independent of the BMI. A role for adiponectin in the development of insulin resistance has been implied in pregnancy. However, no studies have been performed to describe the individual longitudinal course of adiponectin in normal pregnancies. Therefore, we measured serum adiponectin during and after normal pregnancy in 11 healthy women. Serum levels peaked in midpregnancy and the lowest levels were seen in late pregnancy. An inverse association with maternal BMI was observed. [source] Adiponectin, ghrelin, and leptin in cancer cachexia in breast and colon cancer patientsCANCER, Issue 4 2006Ido Wolf M.D. Abstract BACKGROUND The hormone ghrelin and the adipocytokines leptin and adiponectin participate in body weight regulation. In response to weight loss, ghrelin and adiponectin levels increase and leptin decreases. Cancer cachexia is a complex metabolic state, characterized by loss of muscle mass and adipose tissue together with anorexia. The authors hypothesized that responses of these hormones may be attenuated in cancer cachexia. METHODS Fasting plasma ghrelin, adiponectin, and leptin levels, as well as weight loss, were determined in 40 cancer patients: 18 of them suffered from cancer-induced cachexia, and 22 served as a comparison group. Hormone levels were measured before administration of cancer therapy. RESULTS A similar distribution of age, gender, and diagnosis was observed in both study groups, but the cachectic patients had higher rates of metastatic disease and lower albumin levels. No significant correlation was observed between plasma adiponectin levels and weight loss. Mean plasma ghrelin levels were higher among cachectic compared with noncachectic patients. Notably, the association between ghrelin levels and weight loss was only modest, and in a third of the cachectic patients, ghrelin levels were equal to or lower than those in the noncachectic group. Plasma leptin levels showed gender-dependent associations, and significantly lower levels were found among cachectic women but not among cachectic men. CONCLUSIONS Results suggested a gender-dependent attenuation of expected physiologic responses to weight loss among cancer cachexia patients. Thus, impaired response of adiponectin, ghrelin, and leptin may play a role in the pathogenesis of cancer cachexia syndrome. Cancer 2006. © 2006 American Cancer Society. [source] Adiponectin inhibits the growth and peritoneal metastasis of gastric cancer through its specific membrane receptors AdipoR1 and AdipoR2CANCER SCIENCE, Issue 7 2007Makoto Ishikawa Adiponectin, a circulating peptide hormone produced in adipose tissue, has been shown to be reduced in the plasma of patients with cancer, suggesting that this adipokine may be mechanically involved in the pathogenesis of adiposity-related carcinogenesis. In this study, we examined the expression of adiponectin receptors (AdipoR1 and AdipoR2) and assessed the function of adiponectin in gastric cancer. All of the six gastric cancer cell lines significantly expressed mRNA and protein of both receptors with variable levels. Addition of 30 µg/mL adiponectin potently induced apoptosis and inhibited the proliferation of AZ521 and HCG27. Down-regulation of either AdipoR1 or AdipoR2 by specific siRNA significantly suppressed the growth inhibitory effects of adiponectin in both cell lines. Moreover, a local injection of adiponectin markedly inhibited the growth of AZ521 inoculated subcutaneously in nude mice. Similarly, the continuous intraperitoneal infusion of adiponectin effectively suppressed the development of peritoneal metastasis of AZ521. Adiponectin negatively regulates the progression of gastric cancer cells possibly through both AdipoR1 and AdipoR2. Although adiponectin was already reported to have antiangiogenic effects, our results suggest that the antitumor effect of adiponectin was, at least partially, dependent on the direct effects on tumor cells. (Cancer Sci 2007; 98: 1120,1127) [source] Adiponectin levels are high in children with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiencyACTA PAEDIATRICA, Issue 5 2009Thomas MK Völkl Abstract Objective: It has been shown that adiponectin serves as an insulin-sensitizing adipokine. Serum concentrations of adiponectin are low in children with obesity, and increase with fat mass loss, indicating that adiponectin can serve as a biomarker. Since the prevalence of overweight and obesity is increased in children with congenital adrenal hyperplasia (CAH), our study aimed to evaluate serum levels of adiponectin in a cohort of CAH children and adolescents, and their associations with clinical parameters such as chronological age (CA), body mass index (BMI), Tanner stage (TS), medication and metabolic control. Patients and methods: We studied 51 patients, aged between 5.6 and 19.6 years (median 11.8; 30 females, 21 males), cross-sectionally. All patients had genetically confirmed CAH and received standard steroid substitution therapy. Adiponectin was measured by an enzyme linked immunoassay. Since BMI SDS of the CAH cohort were significantly higher compared to the reference population, we built matched pairs with healthy Caucasian subjects from a normal representative cohort for sex, Tanner stage, chronologic age and BMI. Results: Adiponectin concentrations were significantly higher in CAH patients (median 11 ,g/L) compared to the matched controls (6.7 ,g/L, p < 0.0001). Correlation analyses in CAH patients revealed a significant inverse relationship between adiponectin and CA, TS, BMI, serum DHEAS and serum testosterone, but no correlation with hydrocortisone and fludrocortisone dosage. Conclusion: Currently, the importance of the elevated adiponectin concentrations in CAH children for risk assessment is not clear. However, our data imply that besides adequate metabolic control of glucocorticoid substitution, a long-term follow-up of other metabolic markers of insulin resistance should be conducted in CAH patients. [source] Adiponectin: an intriguing hormone for paediatriciansACTA PAEDIATRICA, Issue 6 2008F Savino Abstract Adiponectin, a protein hormone produced by adipocytes, is also found in breast milk, which in turn is implicated in childhood obesity prevention. Although a biological role for adiponectin has not been firmly established, clinical and experimental research indicates that it regulates lipid and glucose metabolism, affects foetal development, and exerts anti-inflammatory and antiatherogenic effects. Conclusion: This review demonstrates an emerging interest of paediatric research on adiponectin. A better understanding of adiponectin's bioactivity might clarify whether breast milk indeed prevents childhood obesity. [source] Circulating adiponectin levels during human endotoxaemiaCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2003P. KELLER SUMMARY Adiponectin, an adipocytokine secreted by fat tissue, may prevent development of diabetes type II, as high adiponectin levels are linked with insulin sensitivity. In contrast, tumour necrosis factor (TNF)- ,, which is also produced by fat tissue, leads to insulin resistance and furthermore inhibits adiponectin mRNA production and secretion of the protein. However, adiponectin also negatively regulates TNF- , levels. Therefore, we set out to test whether an infusion of endotoxin would influence circulating adiponectin levels in healthy human subjects. Twenty-three healthy human subjects were injected with endotoxin (2 ng/kg body weight); eight of these subjects were also injected with saline and served as controls. Plasma levels of adiponectin, TNF- , and interleukin-6 were measured at 0, 1·5, 2, 4, 8 and 24 h. TNF- , and interleukin-6 levels peaked at 1·5 h and 2 h, respectively. Control subjects injected with saline showed a decrease in adiponectin plasma levels with time (P < 0·05) presumably owing to the effect of fasting or physical inactivity. However, there was no change in adiponectin plasma levels in endotoxin injected subjects, thus the effect of fasting was opposed. In conclusion, circulating adiponectin levels are reduced during a resting and fasting state, an effect reversed by endotoxin injection. [source] Insulin, adiponectin, IGFBP-1 levels and body composition in small for gestational age born non-obese children during prepubertal agesCLINICAL ENDOCRINOLOGY, Issue 1 2008Ozlem Sancakli Summary Background, Being small for gestational age (SGA) at birth and postnatal growth pattern may have an impact on insulin resistance and body composition in later life. Adiponectin is a strong determinant of insulin sensitivity. Objective, The aim of this study was to evaluate insulin resistance and adiponectin levels in SGA born children with catch-up growth (CUG) in the absence of obesity in prepubertal ages and relations with body composition and insulin-like growth factor binding protein (IGFBP)-1. Methods, Twenty-four (15F, 9M) SGA born children with CUG but without obesity were evaluated at age 6·3 ± 0·5 years with respect to glucose, insulin, IGFBP-1, leptin and adiponectin levels, and body composition by dual-energy X-ray absorptiometry (DEXA). Their data were compared to that of 62 (27F, 35M) appropriate for gestational age (AGA) children. Results, SGA and AGA children had similar height standard deviation score (SDS) corrected for parental height and body mass index (BMI) SDS. Homeostasis model for insulin resistance (HOMA-IR) was significantly high in SGA (0·7 ± 0·6) than in AGA children (0·4 ± 0·2) (P = 0·029). There were no significant differences in leptin, IGFBP-1, adiponectin, and total and truncal fat between SGA and AGA children. However, being born SGA and having higher BMI in the upper half for the distribution in the sample, although within normal ranges, was associated with lower adiponectin levels (estimated means of log adiponectin levels 3·8 ± 0·3 vs. 4·4 ± 0·1 µg/ml, P = 0·040). Conclusions, SGA children with CUG and with no obesity have higher insulin levels compared to AGA children. Both SGA birth and recent size seem to have an effect on serum adiponectin levels in childhood. [source] Adiponectin is independently associated with insulin sensitivity in women with polycystic ovary syndromeCLINICAL ENDOCRINOLOGY, Issue 6 2004Joachim Spranger Summary objective, The polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance predisposing to diabetes mellitus type 2 and atherosclerosis. Adiponectin is a recently discovered adipocytokine with insulin-sensitizing and putative antiatherosclerotic properties. The aim of the study was to elucidate determinants of circulating adiponectin levels and to investigate the potential role of adiponectin in insulin resistance in PCOS women. patients and measurements, Plasma adiponectin and parameters of obesity, insulin resistance and hyperandrogenism were measured In 62 women with PCOS and in 35 healthy female controls. results, Both in PCOS and controls, adiponectin levels were lower in overweight or obese women than in normal-weight women, without any difference between PCOS and controls after adjustment for body mass index (BMI). In PCOS and in controls there was a significant correlation of adiponectin with BMI (r = ,0·516, P < 0·001), fasting insulin (r = ,0·404, P < 0·001), homeostasis model sensitivity (HOMA %S) (r = ,0·424, P < 0·001) and testosterone (r = ,0·279, P < 0·01), but no correlation with androstenedione (r = ,0·112, P = 0·325), 17-OH-progesterone (r =,0·031, P = 0·784) or the LH/FSH ratio (r =,0·033, P = 0·753). Multiple linear regression analysis revealed that BMI and HOMA %S but not testosterone were independently associated with adiponectin plasma levels, explaining 16% (BMI) and 13% (HOMA %S) of the variability of adiponectin, respectively. In PCOS patients insulin sensitivity, as indicated by continuous infusion of glucose with model assessment (CIGMA %S) was significantly correlated with adiponectin (r = 0·55; P < 0·001), BMI (r =,0·575; P < 0·001), waist-to-hip ratio (WHR) (r =,0·48; P = 0·001), body fat mass assessed by dual-energy X-ray-absorptiometry (DEXA) [Dexa-fat (total) (r = ,0·61; P < 0·001) and Dexa-fat (trunk) (r = ,0·59; P < 0·001)] and with testosterone (r = ,0·42; P = 0·001). Multiple linear regression analysis demonstrated that markers of obesity such as BMI, total or truncal fat mass, age and adiponectin were independently associated with CIGMA %S, and that circulating adiponectin accounted for about 18% of the degree of insulin resistance in PCOS. By contrast, testosterone was not a significant factor, suggesting that PCOS per se did not affect insulin sensitivity independent from obesity, age and adiponectin. Metformin treatment for 6 months in insulin-resistant PCOS women (n = 9) had no effect on plasma adiponectin (P = 0·59) despite significant loss of weight and fat mass and improvement in hyperandrogenaemia. conclusions, PCOS per se is not associated with decreased levels of plasma adiponectin. However, circulating adiponectin is independently associated with the degree of insulin resistance in PCOS women and may contribute to the development and/or maintenance of insulin resistance independent from adiposity. [source] Cord plasma concentrations of adiponectin and leptin in healthy term neonates: positive correlation with birthweight and neonatal adiposityCLINICAL ENDOCRINOLOGY, Issue 1 2004Po-Jung Tsai Summary objective, Adiponectin is negatively associated with leptin, insulin and obesity in children and adults. Whereas increases in fetal insulin and leptin are associated with increased weight and adiposity at birth, the role of adiponectin in fetal growth has not yet been determined. The aims of this study were to examine the relationships between adiponectin and insulin, leptin, weight and adiposity at birth in healthy term infants. design and methods, Anthropometric parameters including weight, length, circumferences and skinfold thickness were measured, and plasma lipid profiles, insulin, leptin and adiponectin concentrations in cord blood samples from 226 singleton infants born at term after uncomplicated pregnancies were assayed. results, Cord plasma adiponectin, leptin and insulin levels correlated significantly and positively with birthweight (P = 0·001, P < 0·001, P < 0·001, respectively) and the sum of skinfold thicknesses (P < 0·001, P < 0·001, P < 0·001, respectively). Mean cord plasma adiponectin and leptin levels, but not insulin level, were significantly higher in large-for-gestational-age (LGA) infants compared with appropriate-for-gestational-age (AGA) infants. Cord plasma leptin concentration, but not adiponectin concentration, was significantly higher in female infants than in male infants (P = 0·003 and P = 0·94, respectively). Cord plasma adiponectin concentration correlated positively with leptin level (P = 0·007) but not with insulin level (P = 0·78). conclusions, High adiponectin levels are present in the cord blood. Cord plasma adiponectin and leptin levels are positively correlated with birthweight and adiposity. This suggests that adiponectin may be involved in regulating fetal growth. [source] AMPK-dependent hormonal regulation of whole-body energy metabolismACTA PHYSIOLOGICA, Issue 1 2009N. L. Dzamko Abstract AMP-dependent protein kinase (AMPK) is an evolutionarily conserved serine/threonine protein kinase central to the regulation of energy balance at both the cellular and whole-body levels. In its classical role as an intracellular metabolic stress-sensing kinase, AMPK switches on fatty acid oxidation and glucose uptake in muscle, while switching off hepatic gluconeogenesis. AMPK also has a broader role in metabolism through the control of appetite. Regulation of AMPK activity at the whole-body level is coordinated by a growing number of hormones and cytokines secreted from adipose tissue, skeletal muscle, pancreas and the gut including leptin, adiponectin, insulin, interluekin-6, resistin, TNF-, and ghrelin. Understanding how these secreted signalling proteins regulate AMPK activity to control fatty acid oxidation, glucose uptake, gluconeogenesis and appetite may yield therapeutic treatments for metabolic disorders such as diabetes, insulin resistance and obesity. 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