Dataset Information

Associations of adiponectin, resistin, and tumor necrosis factor-alpha with insulin resistance.

ABSTRACT: Adipose tissue-derived adipokines may contribute to insulin resistance.We tested the hypothesis that adipokines are associated with insulin resistance in a community-based cohort and that associations are maintained in people with and without the metabolic syndrome (high vs. low risk of diabetes).We studied a cross-sectional sample of 2356 individuals attending the seventh examination (1998-2001) of the Framingham Offspring Study. We measured levels of glucose, insulin, adiponectin, resistin, and TNFalpha in fasting blood samples and defined metabolic syndrome by updated National Cholesterol Education Program criteria. We used ANOVA to test associations of adipokines with insulin resistance and multivariable logistic regression models to assess joint associations of adipokines and metabolic syndrome with insulin resistance.Homeostasis model (HOMA-IR), with insulin resistance defined by HOMA-IR greater than the 75th percentile, was measured.Age- and sex-adjusted HOMA-IR levels were inversely related to adiponectin (r = -0.40, P < 0.0001) and positively related to resistin (r = 0.13, P < 0.0001) and TNFalpha (r = 0.12, P < 0.0001). The prevalence of insulin resistance increased with decreasing tertiles of adiponectin (from 10.9% in the third to 42.5% in the first tertile; P < 0.0001) and increasing tertiles of resistin (from 19.3 to 30.9%; P < 0.0001) and TNFalpha (from 18.8 to 32.0%; P < 0.0001). Results were similar after adjustment for body mass index. These associations were present in individuals with or without the metabolic syndrome. In multivariable regression models, metabolic syndrome and adipokines individually and jointly were significantly associated with insulin resistance.Adverse levels of adipokines are associated with insulin resistance in individuals at low or high diabetes risk.

SUBMITTER: Hivert MF

PROVIDER: S-EPMC2515087 | biostudies-other | 2008 Aug

REPOSITORIES: biostudies-other

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Associations of adiponectin, resistin, and tumor necrosis factor-alpha with insulin resistance.

Hivert Marie-France MF Sullivan Lisa M LM Fox Caroline S CS Nathan David M DM D'Agostino Ralph B RB Wilson Peter W F PW Meigs James B JB

The Journal of clinical endocrinology and metabolism 20080520 8

<h4>Context</h4>Adipose tissue-derived adipokines may contribute to insulin resistance.<h4>Objective</h4>We tested the hypothesis that adipokines are associated with insulin resistance in a community-based cohort and that associations are maintained in people with and without the metabolic syndrome (high vs. low risk of diabetes).<h4>Design, setting, and participants</h4>We studied a cross-sectional sample of 2356 individuals attending the seventh examination (1998-2001) of the Framingham Offspr ...[more]

PMID: 18492747

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Project description:Obesity is often associated with insulin resistance, low-grade systemic inflammation, and reduced plasma adiponectin. Inflammation is also increased in adipose tissue, but it is not clear whether the reductions of adiponectin levels are related to dysregulation of insulin activity and/or increased proinflammatory mediators. In this study, we investigated the interactions of insulin, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in the regulation of adiponectin production using in vivo and in vitro approaches. Plasma adiponectin and parameters of insulin resistance and inflammation were assessed in a cohort of lean and obese insulin-resistant subjects. In addition, the effect of insulin was examined in vivo using the hyperinsulinemic-euglycemic clamp, and in adipose tissue (AT) cultures. Compared with lean subjects, the levels of total adiponectin, and especially the high-molecular-weight (HMW) isomer, were abnormally low in obese insulin-resistant subjects. The hyperinsulinemic clamp data confirmed the insulin-resistant state in the obese patients and showed that insulin infusion significantly increased the plasma adiponectin in lean but not obese subjects (P < 0.01). Similarly, insulin increased total adiponectin release from AT explants of lean and not obese subjects. Moreover, expression and secretion of TNF-α and IL-6 increased significantly in AT of obese subjects and were negatively associated with expression and secretion of adiponectin. In 3T3-L1 and human adipocyte cultures, insulin strongly enhanced adiponectin expression (2-fold) and secretion (3-fold). TNF-α, and not IL-6, strongly opposed the stimulatory effects of insulin. Intriguingly, the inhibitory effect of TNF-α was especially directed toward the HMW isomer of adiponectin. In conclusion, these studies show that insulin upregulates adiponectin expression and release, and that TNF-α opposes the stimulatory effects of insulin. A combination of insulin resistance and increased TNF-α production could explain the decline of adiponectin levels and alterations of isomer composition in plasma of obese insulin-resistant subjects.

Project description:Although coffee consumption has been historically associated with negative health outcomes, recent evidence suggests a lower risk of metabolic syndrome, obesity and diabetes among regular coffee drinkers. Among the plethora of minor organic compounds assessed as potential mediators of coffee health benefits, trigonelline and its pyrolysis product N-methylpyridinium (NMP) were preliminary shown to promote glucose uptake and exert anti-adipogenic properties. Against this background, we aimed at characterizing the effects of trigonelline and NMP in inflamed and dysfunctional human adipocytes. Human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were treated with NMP or, for comparison, trigonelline, for 5 h before stimulation with tumor necrosis factor (TNF)-α. NMP at concentrations as low as 1 µmol/L reduced the stimulated expression of several pro-inflammatory mediators, including C-C Motif chemokine ligand (CCL)-2, C-X-C Motif chemokine ligand (CXCL)-10, and intercellular adhesion Molecule (ICAM)-1, but left the induction of prostaglandin G/H synthase (PTGS)2, interleukin (IL)-1β, and colony stimulating factor (CSF)1 unaffected. Furthermore, NMP restored the downregulated expression of adiponectin (ADIPOQ). These effects were functionally associated with downregulation of the adhesion of monocytes to inflamed adipocytes. Under the same conditions, NMP also reversed the TNF-α-mediated suppression of insulin-stimulated Ser473 Akt phosphorylation and attenuated the induction of TNF-α-stimulated lipolysis restoring cell fat content. In an attempt to preliminarily explore the underlying mechanisms of its action, we show that NMP restores the expression of the master regulator of adipocyte differentiation peroxisome proliferator-activated receptor (PPAR)γ and downregulates activation of the pro-inflammatory mitogen-activated protein jun N-terminal kinase (JNK). In conclusion, NMP reduces adipose dysfunction in pro-inflammatory activated adipocytes. These data suggest that bioactive NMP in coffee may improve the inflammatory and dysmetabolic milieu associated with obesity.

Project description:BackgroundTumor necrosis factor-α (TNF-α) may play an important role in the recalcitrant inflammatory and hyperproliferative dermatosis of psoriasis, and there may be a relationship between TNF-α polymorphisms and psoriasis risk.MethodsWe performed a meta-analysis to evaluate the associations between TNF-α polymorphisms and psoriasis. Electronic searches of Pubmed, Embase, and Web of Science were performed for all publications on the associations between TNF-α polymorphisms and psoriasis through September 26, 2012. The pooled odds ratios (ORs) with their 95% confidence interval (95%CIs) were calculated to assess the associations.ResultsSixteen case-control studies with a total of 2,253 psoriasis cases and 1,947 controls on TNF-α 308 G/A polymorphism and fourteen studies on TNF-α 238 G/A polymorphism with 2,104 cases and 1,838 controls were finally included into the meta-analysis. Overall, TNF-α 308 G/A polymorphism was significantly associated with decreased risk of psoriasis under three genetic comparison models (for A versus G: fixed-effects OR 0.71, 95%CI 0.62-0.82, P < 0.001; for AG versus GG: fixed-effects OR 0.67, 95%CI 0.57-0.78, P < 0.001; for AA/AG versus GG: fixed-effects OR 0.67, 95%CI 0.58-0.78, P < 0.001). In addition, TNF-α 238 G/A polymorphism was associated with increased risk of psoriasis under three genetic models (for A versus G: fixed-effects OR 2.46, 95%CI 2.04-2.96, P < 0.001; for AG versus GG: fixed-effects OR 2.69, 95%CI 2.20-3.28, P < 0.001; for AA/AG versus GG: fixed-effects OR 2.68, 95%CI 2.20-3.26, P < 0.001). Subgroup analysis by ethnicity identified a significant association between TNF-α 308 G/A polymorphism and decreased risk of psoriasis in both Caucasians and Asians and a significant association between TNF-α 238 G/A polymorphism and increased risk of psoriasis in Caucasians.ConclusionsThe meta-analysis suggests that TNF-α 308 G/A polymorphism is associated with decreased risk of psoriasis, while TNF-α 238 G/A is associated with increased risk of psoriasis.

Dataset Information

Associations of adiponectin, resistin, and tumor necrosis factor-alpha with insulin resistance.

Publications

Associations of adiponectin, resistin, and tumor necrosis factor-alpha with insulin resistance.

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