Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes

Faßhauer, Mathias; Kralisch, Susan; Klier, Margit; Lössner, Ulrike; Blüher, Matthias; Klein, Johannes; Paschke, Ralf

doi:10.1016/s0006-291x(03)00090-1

Cited by 482 publications

(310 citation statements)

References 30 publications

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“…Of these, IL-6 and leptin were considered in this study. IL-6 has been proposed as a potent regulator of adiponectin secretion [9] and sufficient quantities of leptin are thought to be required for normal adiponectin function. Although both were noted to associate positively with glucose intolerance in these individuals, neither correlated with S A or total adiponectin.…”

Section: Discussionmentioning

confidence: 99%

Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males

et al. 2005

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Aims/hypothesis: It is well established that total systemic adiponectin is reduced in type 2 diabetic subjects. To date most studies have been concerned with the singular full-length protein or proteolytically cleaved globular domain. It is, however, apparent that the native protein circulates in serum as a lower molecular weight hexamer and as larger multimeric structures of high molecular weight (HMW). In this study we address the clinical significance of each form of the protein with respect to glucose tolerance. Methods: Serum was obtained from 34 Indo-Asian male subjects (BMI 26.5±3.1; age 52.15±10.14 years) who had undertaken a 2-h oral glucose tolerance test. An aliquot of serum was fractionated using velocity sedimentation followed by reducing SDS-PAGE. Western blots were probed for adiponectin, and HMW adiponectin as a percentage of total adiponectin (percentage of higher molecular weight adiponectin [S A ] index) was calculated from densitometry readings. Total adiponectin was measured using ELISA; leptin, insulin and IL-6 were determined using ELISA. Results: Analysis of the cohort demonstrated that total adiponectin (r=0.625, p=0.0001), fasting insulin (r=−0.354, p=0.040) and age (r=0.567, p=0.0001) correlated with S A . S A showed a tighter, inverse correlation with 2-h glucose levels (r=−0.58, p=0.0003) than total adiponectin (r=−0.38, p=0.0001). Conclusions/interpretation: This study demonstrates the importance of the S A index as a better determinant of glucose intolerance than measurements of total adiponectin. Our findings suggest that HMW adiponectin is the active form of the protein.

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Section: Discussionmentioning

confidence: 99%

Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males

et al. 2005

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“…Some other studies have reported similar disassociation between adiponectin levels and insulin resistance 28,29 and the relationship between adiponectin and IR is probably not one of the direct cause and effect in all patients. It is possible that their inverse relationship may be mediated not only by insulin levels but also by other hormones such as catecholamines or androgens, [30][31][32] as well as by pro-inflammatory cytokines, 33,34 and some medications. 31,35 Our results also depict the prominent role that adipose tissue plays in both insulin resistance and the clinical expression of the metabolic syndrome (Figures 1 and 2).…”

Section: Discussionmentioning

confidence: 99%

Adiponectin, insulin resistance and clinical expression of the metabolic syndrome in patients with Type 2 diabetes

et al. 2006

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Background: Obesity and the metabolic syndrome have emerged as clinical and public health crises in many populations, but not all obese patients have the syndrome. As adipocytes produce several adipokines that modulate insulin action as well as glucose and lipid metabolism, we postulate that estimation of adipokines may be useful addition to the criteria used to identify obese individuals with the metabolic syndrome. Objective: To evaluate the determinants and associations of plasma adiponectin in relation to the metabolic syndrome in patients with Type 2 diabetes. Design: Cross-sectional study. Setting: General Teaching Hospital. Patients: One hundred and thirty five (57 M, 78 F) patients with Type 2 diabetes mellitus. Measurements: Adiponectin, leptin, high-sensitivity C-reactive protein (hs-CRP), fasting plasma insulin, glucose, glycated hemoglobin and full lipid profile. Patients were classified on the basis of the degree of adiposity, insulin resistance (IR) (homeostasis model assessment of insulin resistance (HOMA-IR)) and the number of the American Heart Association and the National Heart, Lung and Blood Institute criteria of the metabolic syndrome. Results: Adiponectin levels were inversely correlated with age, indices of obesity, IR and hs-CRP. Overweight/obese and nonobese insulin-sensitive patients had significantly higher (Po0.05) adiponectin levels than those with IR despite similar body mass index and waist circumference. Therefore, within each category of obesity stratification, lower adiponectin levels were associated with IR. Adiponectin showed stepwise decrease with increasing number of the criteria for diagnosis of the metabolic syndrome. Using multiple logistic regression, the odds ratio of the metabolic syndrome as predicted by adiponectin was 0.73 (95% confidence interval 0.53-0.96; P ¼ 0.04). At cutoff point of 18 ng/ml, the diagnostic sensitivity and specificity of adiponectin for the metabolic syndrome were 83 and 65%, respectively, in male patients and 92 and 41%, respectively, in female patients. Receiver operating characteristic analysis showed that adiponectin had significantly higher area under the curve compared with leptin, leptin:adiponectin ratio and triglycerides for the detection of the metabolic syndrome. Conclusions: In patients with Type 2 diabetes, adiponectin concentrations are closely related to IR and the components of the metabolic syndrome. Adiponectin concentration may be a useful addition to the criteria used for identifying obese subjects with the metabolic syndrome.

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“…8,19 Several in vitro studies have clearly demonstrated that, cytokines such as IL-6, IL-8, IL-1b and TNF-a are potent inhibitors of adiponectin. 20,28,33 Recently, it was shown that weight reduction in obese subjects leads to a marked decrease in proinflammatory proteins. 5 These proteins, adipose tissue and insulin resistance, seem to be partly involved in the process causing chronic subclinical inflammation, associated with cardiovascular disease.…”

Section: Discussionmentioning

confidence: 99%

Effects of marked weight loss on plasma levels of adiponectin, markers of chronic subclinical inflammation and insulin resistance in morbidly obese women

et al. 2005

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OBJECTIVE:Obesity is linked to the insulin resistance syndrome (IRS), type 2 diabetes (T2D) and cardiovascular disease. Markers of chronic subclinical inflammation such as high-sensitive C-reactive protein (hs-CRP) and interleukin 6 (IL-6) are closely related to insulin resistance and obesity. Recent evidence suggests that adiponectin, a protein whose circulating levels are decreased in obesity, has anti-inflammatory properties, and also appears to enhance potently insulin action and therefore appears to function as a signal produced by adipose tissue that influences whole-body glucose metabolism. SUBJECTS AND METHODS: We investigated the cross-sectional and longitudinal association of adiponectin with CRP and IL-6 in 41 morbidly obese women with different stages of glucose tolerance before and 17 months after significant weight loss induced by gastric surgery. Adiponectin was measured by RIA. CRP and IL-6 were determined by commercially available ELISA systems. RESULTS: Weight loss induced a significant shift from T2D (preoperatively 34% vs postoperatively 2%) to impaired glucose tolerance (IGT) (37% preoperatively vs 30% postoperatively) and normal glucose tolerance (NGT) (29% preoperatively vs 68% postoperatively). Preoperatively adiponectin levels were negatively correlated with CRP (r ¼ À0.59, Po0.0006), IL-6 (r ¼ À0.42, Po0.02) and leukocytes (r ¼ À0.41, Po0.007). After gastroplasty, adiponectin concentrations increased significantly (15.478.2 vs 19.876.2 mg/ml, Po0.005) associated with changes of weight and body mass index (r ¼ À0.45, Po0.007; r ¼ À0.35, Po0.04). Furthermore, preoperative CRP was significantly associated with changes in adiponectin even after adjustment for sex, age, preoperative body mass index (BMI) impaired glucose metabolism and changes in BMI and changes in BMI (standardized beta 0.61, P ¼ 0.005). CONCLUSION: Levels of adiponectin, which are associated with markers of chronic subclinical inflammation, could be significantly increased after weight loss in morbidly obese patients. This increase was more pronounced in patients with NGT compared to those with T2D and IGT. Preoperative levels of CRP are predictive for changes of adiponectin after weight loss.

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Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes

Cited by 482 publications

References 30 publications

Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males

Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males

Adiponectin, insulin resistance and clinical expression of the metabolic syndrome in patients with Type 2 diabetes

Effects of marked weight loss on plasma levels of adiponectin, markers of chronic subclinical inflammation and insulin resistance in morbidly obese women

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