Diabetologia. 2013 Oct;56(10):2275-85.

Circulating miR-130b mediates metabolic crosstalk between fat and muscle in overweight/obesity.

Yu-cheng Wang, Yuying Li, Xin-yi Wang, Duo Zhang, Huihui Zhang, Qi Wu, Yu-qing He, Jian-ying Wang, Lian Zhang, Hongfeng Xia, Jun Yan, Xihua Li, Hao Ying

Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, People’s Republic of China.

 

Abstract

AIMS/HYPOTHESIS:

Adipose tissue is a dynamic endocrine organ that regulates whole-body energy homeostasis through the secretion of signalling molecules. Recent reports suggest that secreted microRNAs (miRNAs) may function as biologically active molecules for intercellular communication and the level of circulating miRNAs correlated with many disease. This study aims to identify obesity-related circulating miRNA that could be secreted from adipocytes and to explore its possible role in the pathogenesis of metabolic diseases.

METHODS:

Real-time RT-PCR was used to evaluate the circulating level of miR-130b in mouse models of obesity as well as in humans. Luciferase assay and immunoblotting were used to verify the miRNA target. The effect of miR-130b on mouse peroxisome proliferator-activated receptor γ coactivator-1α was also investigated by electrogene transfer.

RESULTS:

The circulating level of miR-130b was elevated in mouse models of obesity as well as in obese Chinese individuals. More interestingly, the circulating level of miR-130b was positively correlated with BMI. Moreover, circulating miR-130b was a better predictor of the metabolic syndrome than was triacylglycerol level. Mechanistically, adipocytes secreted miR-130b during adipogenesis. TGF-β, which is proportionately increased with obesity, stimulated miR-130b secretion from adipocytes. Furthermore, miR-130b was able to target muscle cells and reduce the expression of its direct target gene, PGC-1α (also known as PPARGC1A), which plays a key role in lipid oxidation in muscle.

CONCLUSIONS/INTERPRETATION:

Circulating miR-130b reflects the degree of obesity and could serve as a potential biomarker for hypertriacylglycerolaemia and metabolic syndrome. Circulating miR-130b could function as a metabolic mediator for adipose-muscle crosstalk and might be involved in the pathogenesis of obesity-associated metabolic diseases. Our findings presented here help us to further understand the molecular mechanisms that link obesity and obesity-related metabolic diseases and provide us with new therapeutic targets for defeating obesity-related diseases.

PMID: 23868745

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