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MicroRNA-425 controls lipogenesis and lipolysis in adipocytes

Author:
Qi, Renli, Wang, Jing, Wang, Qi, Qiu, Xiaoyu, Yang, Feiyun, Liu, Zuohua, Huang, Jinxiu
Source:
Biochimica et biophysica acta 2019
ISSN:
1388-1981
Subject:
adenosine triphosphate, adipocytes, adipogenesis, body fat, energy balance, genes, growth and development, lipid peroxidation, lipogenesis, lipolysis, mice, microRNA, obesity
Abstract:
An increasing number of studies have demonstrated that some microRNAs participate in the regulation of growth and development of adipocytes. The present study shows that microRNA-425-5p (miR-425) is a novel strong regulator of adipogenesis and adipolysis in adipocytes. Forced expression of miR-425 in mice promoted body fat accumulation and the development of obesity due to high-fat intake, whereas silencing miR-425 prevented mice from being obese. Mechanically, the expression of miR-425 is controlled by PPARĪ³ during the adipogenesis process in adipocytes. MiR-425 overexpression resulted in a reduction in the proliferation of 3t3-L1 pre-adipocytes but significantly accelerated cellular adipogenic differentiation. Mapk14, a negative regulator of adipogenesis, was predicted and confirmed as a real target gene of miR-425. Moreover, knocking down miR-425 remarkably intensified intracellular lipolysis and promoted lipid oxidation, which is related to the activation of AMPK, a monitor for intracellular energy balance. MiR-425 activated AMPK not only by decreasing cellular ATP concentrations but also by targeting the gene of Cab39, which is an upstream co-activator of AMPK. The findings of the present study suggest that miR-425 could control adipogenesis and adipolysis in adipocytes by simultaneously triggering multidirectional targets.
Agid:
6342132