Dataset Information

Genetic variants of adiponectin receptor 2 are associated with increased adiponectin levels and decreased triglyceride/VLDL levels in patients with metabolic syndrome.

ABSTRACT: BACKGROUND: Adiponectin acts as an antidiabetic, antiinflammatory and antiatherogenic adipokine. These effects are assumed to be mediated by the recently discovered adiponectin receptors AdipoR1 and AdipoR2. AIM: The purpose of this study was to determine whether variations in the AdipoR1 and AdipoR2 genes may contribute to insulin resistance, dyslipidemia and inflammation. METHODS: We sequenced all seven coding exons of both genes in 20 unrelated German subjects with metabolic syndrome and tested genetic variants for association with glucose, lipid and inflammatory parameters. RESULTS: We identified three AdipoR2 variants (+795G/A, +870C/A and +963C/T) in perfect linkage disequilibrium (r2 = 1) with a minor allele frequency of 0.125. This haplotype was associated with higher plasma adiponectin levels and decreased fasting triglyceride, VLDL-triglyceride and VLDL-cholesterol levels. No association, however, was observed between the AdipoR2 SNP cluster and glucose metabolism. CONCLUSION: To our knowledge, this is the first study to identify an association between genetic variants of the adiponectin receptor genes and plasma adiponectin levels. Furthermore, our data suggest that AdipoR2 may play an important role in triglyceride/VLDL metabolism.

SUBMITTER: Broedl UC

PROVIDER: S-EPMC1482678 | biostudies-literature | 2006

REPOSITORIES: biostudies-literature

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Genetic variants of adiponectin receptor 2 are associated with increased adiponectin levels and decreased triglyceride/VLDL levels in patients with metabolic syndrome.

Broedl Uli C UC Lehrke Michael M Fleischer-Brielmaier Elisabeth E Tietz Anne B AB Nagel Jutta M JM Göke Burkhard B Lohse Peter P Parhofer Klaus G KG

Cardiovascular diabetology 20060515

<h4>Background</h4>Adiponectin acts as an antidiabetic, antiinflammatory and antiatherogenic adipokine. These effects are assumed to be mediated by the recently discovered adiponectin receptors AdipoR1 and AdipoR2.<h4>Aim</h4>The purpose of this study was to determine whether variations in the AdipoR1 and AdipoR2 genes may contribute to insulin resistance, dyslipidemia and inflammation.<h4>Methods</h4>We sequenced all seven coding exons of both genes in 20 unrelated German subjects with metaboli ...[more]

PMID: 16700915

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Project description:To assess basal and insulin-mediated VLDL-triglyceride (TG) kinetics and the relationship between VLDL-TG secretion and hepatic insulin resistance assessed by endogenous glucose production (EGP) in obese and lean men.A total of 12 normoglycemic, obese (waist-to-hip ratio >0.9, BMI >30 kg/m(2)) and 12 lean (BMI 20-25 kg/m(2)) age-matched men were included. Ex vivo-labeled [1-(14)C]VLDL-TGs and [3-(3)H]glucose were infused postabsorptively and during a hyperinsulinemic-euglycemic clamp to determine VLDL-TG kinetics and EGP. Body composition was determined by dual X-ray absorptiometry and computed tomography scanning. Energy expenditure and substrate oxidation rates were measured by indirect calorimetry.Basal VLDL-TG secretion rates were increased in obese compared with lean men (1.25 ± 0.34 vs. 0.86 ± 0.34 ?mol/kg fat-free mass [FFM]/min; P = 0.011), whereas there was no difference in clearance rates (150 ± 56 vs. 162 ± 77 mL/min; P = NS), resulting in greater VLDL-TG concentrations (0.74 ± 0.40 vs. 0.38 ± 0.20 mmol/L; P = 0.011). The absolute insulin-mediated suppression of VLDL-TG secretion was similar in the groups. However, the percentage reduction (-36 ± 18 vs. -54 ± 10%; P = 0.008) and achieved VLDL-TG secretion rates (0.76 ± 0.20 vs. 0.41 ± 0.19 ?mol/kg FFM/min; P < 0.001) were impaired in obese men. Furthermore, clearance rates decreased significantly in obese men, but there was no significant change in lean men (-17 ± 18 vs. 7 ± 20%; P = 0.007), resulting in less percentage reduction of VLDL-TG concentrations in obese men (-22 ± 20 vs. -56 ± 11%; P < 0.001). Insulin-suppressed EGP was similar (0.4 [0.0-0.8] vs. 0.1 [0.0-1.2] mg/kg FFM/min (median [range]); P = NS), and the percentage reduction was equivalent (-80% [57-98] vs. -98% [49-100], P = NS). Insulin-mediated glucose disposal was significantly reduced in obese men.Basal VLDL-TG secretion rates are increased in normoglycemic but insulin-resistant, obese men, resulting in hypertriglyceridemia. Insulin-mediated suppression of EGP is preserved in obese men, whereas suppression of VLDL-TG secretion is less pronounced in obese men. Compared with EGP, the inability to achieve suppression of VLDL-TG secretions to a level similar to control subjects during hyperinsulinemia seems to be an early manifestation in male obesity.

Dataset Information

Genetic variants of adiponectin receptor 2 are associated with increased adiponectin levels and decreased triglyceride/VLDL levels in patients with metabolic syndrome.

Publications

Genetic variants of adiponectin receptor 2 are associated with increased adiponectin levels and decreased triglyceride/VLDL levels in patients with metabolic syndrome.

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