Regulation of adiponectin by adipose tissue-derived cytokines: in vivo  and in vitro investigations in humans

Bruun, Jens Meldgaard; Lihn, Aina S.; Verdich, Camilla; Pedersen, Steen; Toubro, Søren; Astrup, Arne; Richelsen, Bjørn

doi:10.1152/ajpendo.00110.2003

Cited by 665 publications

(509 citation statements)

References 43 publications

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“…The molecular mechanisms involved in adiponectin secretion and multimerization as well as their regulation have not been deciphered. 10 However, it is clear that reactive oxygen species 29 and pro-inflammatory cytokines 30 are potent inhibitors of adiponectin gene expression. As BJ has a very high anti-oxidant activity, more than four times greater than NJ, 18,31 it could reduce oxidative stress in obese diabetic mice.…”

Section: Discussionmentioning

confidence: 99%

Antiobesity and antidiabetic effects of biotransformed blueberry juice in KKAy mice

et al. 2009

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Aim: Biotransformation of blueberry juice by the Serratia vaccinii bacterium gave rise to adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and glucose uptake in muscle cells and adipocytes, but inhibited adipogenesis. This study investigated the antiobesity and antidiabetic potential of biotransformed blueberry juice (BJ) in KKA y mice, rodent model of leptin resistance. Methods: BJ was incorporated in drinking water of KKA y mice. Parameters of body weight, food intake, plasma glucose, insulin, leptin, and adiponectin were measured. Before and after therapy, animals were subjected to an oral glucose tolerance test. At the end of treatment, liver, muscle, kidney, epididymal fat pad, abdominal fat pad, and dorsal fat pad were collected and weighed. Results: Incorporating BJ in drinking water protected young KKA y mice from hyperphagia and significantly reduced their weight gain. Moreover, BJ protected young KKA y mice against the development of glucose intolerance and diabetes mellitus. Chronic BJ administration in obese and diabetic KKA y mice reduced food intake and body weight. This effect could not fully explain the associated antidiabetic effect because BJ-treated mice still showed lower blood glucose level when compared with pair-fed controls. The adipokines pathway also seems to be involved because BJ significantly increased adiponectin levels in obese mice. Conclusions: This study shows that BJ decreases hyperglycemia in diabetic mice, at least in part by reversing adiponectin levels. BJ also protects young pre-diabetic mice from developing obesity and diabetes. Thus, BJ may represent a novel complementary therapy and a source of novel therapeutic agents against diabetes mellitus.

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Section: Discussionmentioning

confidence: 99%

Antiobesity and antidiabetic effects of biotransformed blueberry juice in KKAy mice

et al. 2009

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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%

“…19 In vitro incubation of human adipose tissue with IL-6 resulted in a decrement in adiponectin mRNA levels, suggesting that cytokines may inhibit adiponectin and so playing an important role in the association between adiponectin and insulin resistance. 20 However, none of these studies provided data of adiponectin comparing patients with different stages of glucose tolerance. Therefore, we investigated the cross-sectional and longitudinal association of adiponectin plasma levels with CRP and IL-6 in morbidly obese women with normal (NGT) and impaired glucose tolerance (IGT) as well as T2D before and after gastroplastic surgery.…”

Section: Introductionmentioning

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 is an anti-inflammatory adipokine that has an insulin-like role in promoting vasodilatation and anti-atherosclerotic effects, stimulating nitric oxide production in endothelial cells and inhibiting the release of proinflammatory adipokines, which in turn contribute to a coupling of vascular insulin resistance and endothelial dysfunction. 8,9 Moreover, a decrease in insulin sensitivity is related to increases in the endothelial expression of plasminogen activator inhibitor type-1 (PAI-1) and cellular/vascular adhesion molecules implicated in the initiation of endothelial dysfunction. 4,9,10 The prevalence of cardiovascular diseases in children and adolescents is increasing, and there is evidence that carotid IMT is higher in children with diabetes, hypercholesterolemia and obesity than in healthy controls.…”

Section: Introductionmentioning

confidence: 99%

Improvement in HOMA-IR is an independent predictor of reduced carotid intima-media thickness in obese adolescents participating in an interdisciplinary weight-loss program

et al. 2010

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The aim of this study was to verify whether a 1-year interdisciplinary weight-loss program improved common carotid artery intima-media thickness (IMT) and whether insulin resistance and/or inflammation (as measured by the markers plasminogen activator inhibitor type-1 and adiponectin) might underlie obesity in adolescents. A group of 29 post-pubescent obese adolescents were submitted to an interdisciplinary intervention over the course of 1 year. Common carotid artery IMT was determined ultrasonographically. Body composition, blood pressure (BP), glycemia, insulinemia, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile and adipokine concentrations were analyzed before and after the intervention. The interdisciplinary weight-loss program promoted a significant improvement in body composition, insulin concentration, HOMA-IR, lipid profile, BP and inflammatory state, in addition to significantly decreasing the common carotid artery IMT. Furthermore, this study demonstrated that the difference between baseline and final values of HOMA-IR (DHOMA-IR) was negatively correlated with concomitant changes in the adiponectin concentration (Dadiponectin; r¼À0.42; P¼0.02) and positively correlated with changes in common carotid artery IMT (Dcarotid IMT; r¼0.41; P¼0.03). Multiple regression analysis adjusted by age, cardiovascular risk factors and inflammatory markers showed that DHOMA-IR was an independent predictor of significant changes in common carotid artery IMT. This investigation demonstrated that an interdisciplinary weight-loss program promoted a reduction of the common carotid artery IMT in obese Brazilian adolescents, and the improvement of HOMA-IR was an independent predictor of carotid IMT changes in this population.

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Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans

Cited by 665 publications

References 43 publications

Antiobesity and antidiabetic effects of biotransformed blueberry juice in KKAy mice

Antiobesity and antidiabetic effects of biotransformed blueberry juice in KKAy mice

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

Improvement in HOMA-IR is an independent predictor of reduced carotid intima-media thickness in obese adolescents participating in an interdisciplinary weight-loss program

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