Dataset Information

Enhanced metabolic flexibility associated with elevated adiponectin levels.

ABSTRACT: Metabolically healthy individuals effectively adapt to changes in nutritional state. Here, we focus on the effects of the adipocyte-derived secretory molecule adiponectin on adipose tissue in mouse models with genetically altered adiponectin levels. We found that higher adiponectin levels increased sensitivity to the lipolytic effects of adrenergic receptor agonists. In parallel, adiponectin-overexpressing mice also display enhanced clearance of circulating fatty acids and increased expansion of subcutaneous adipose tissue with chronic high fat diet (HFD) feeding. These adaptive changes to the HFD were associated with increased mitochondrial density in adipocytes, smaller adipocyte size, and a general transcriptional up-regulation of factors involved in lipid storage through efficient esterification of free fatty acids. The physiological response to adiponectin overexpression resembles in many ways the effects of chronic exposure to beta3-adrenergic agonist treatment, which also results in improvements in insulin sensitivity. In addition, using a novel computed tomography-based method for measurements of hepatic lipids, we resolved the temporal events taking place in the liver in response to acute HFD exposure in both wild-type and adiponectin-overexpressing mice. Increased levels of adiponectin potently protect against HFD-induced hepatic lipid accumulation and preserve insulin sensitivity. Given these profound effects of adiponectin, we propose that adiponectin is a factor that increases the metabolic flexibility of adipose tissue, enhancing its ability to maintain proper function under metabolically challenging conditions.

SUBMITTER: Asterholm IW

PROVIDER: S-EPMC2832156 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Enhanced metabolic flexibility associated with elevated adiponectin levels.

Asterholm Ingrid Wernstedt IW Scherer Philipp E PE

The American journal of pathology 20100121 3

Metabolically healthy individuals effectively adapt to changes in nutritional state. Here, we focus on the effects of the adipocyte-derived secretory molecule adiponectin on adipose tissue in mouse models with genetically altered adiponectin levels. We found that higher adiponectin levels increased sensitivity to the lipolytic effects of adrenergic receptor agonists. In parallel, adiponectin-overexpressing mice also display enhanced clearance of circulating fatty acids and increased expansion of ...[more]

PMID: 20093494

Similar Datasets

Project description:ObjectiveGamma-glutamyl dipeptides are bioactive peptides involved in inflammation, oxidative stress, and glucose regulation. Gamma-glutamyl-leucine (Gamma-Glu-Leu) has been extensively reported to be associated with the risk of cardio-metabolic diseases, such as obesity, metabolic syndrome, and type 2 diabetes. However, the causality remains to be uncovered. The aim of this study was to explore the causal-effect relationships between Gamma-Glu-Leu and metabolic risk.Materials and methodsIn this study, 1,289 subjects were included from a cross-sectional survey on metabolic syndrome (MetS) in eastern China. Serum Gamma-Glu-Leu levels were measured by untargeted metabolomics. Using linear regressions, a two-stage genome-wide association study (GWAS) for Gamma-Glu-Leu was conducted to seek its instrumental single nucleotide polymorphisms (SNPs). One-sample Mendelian randomization (MR) analyses were performed to evaluate the causality between Gamma-Glu-Leu and the metabolic risk.ResultsFour SNPs are associated with serum Gamma-Glu-Leu levels, including rs12476238, rs56146133, rs2479714, and rs12229654. Out of them, rs12476238 exhibits the strongest association (Beta = -0.38, S.E. = 0.07 in discovery stage, Beta = -0.29, S.E. = 0.14 in validation stage, combined P-value = 1.04 × 10-8). Each of the four SNPs has a nominal association with at least one metabolic risk factor. Both rs12229654 and rs56146133 are associated with body mass index, waist circumference (WC), the ratio of WC to hip circumference, blood pressure, and triglyceride (5 × 10-5 < P < 0.05). rs56146133 also has nominal associations with fasting insulin, glucose, and insulin resistance index (5 × 10-5 < P < 0.05). Using the four SNPs serving as the instrumental SNPs of Gamma-Glu-Leu, the MR analyses revealed that higher Gamma-Glu-Leu levels are causally associated with elevated risks of multiple cardio-metabolic factors except for high-density lipoprotein cholesterol and low-density lipoprotein cholesterol (P > 0.05).ConclusionFour SNPs (rs12476238, rs56146133, rs2479714, and rs12229654) may regulate the levels of serum Gamma-Glu-Leu. Higher Gamma-Glu-Leu levels are causally linked to cardio-metabolic risks. Future prospective studies on Gamma-Glu-Leu are required to explain its role in metabolic disorders.

Dataset Information

Enhanced metabolic flexibility associated with elevated adiponectin levels.

Publications

Enhanced metabolic flexibility associated with elevated adiponectin levels.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets