MicroRNA-124 promotes hepatic triglyceride accumulation through targeting tribbles homolog 3

MicroRNA-124 通过靶向 tribbles 同源物 3 促进肝脏甘油三酯积累

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作者:Xing Liu, Jiejie Zhao, Qi Liu, Xuelian Xiong, Zhijian Zhang, Yang Jiao, Xiaoying Li, Bin Liu, Yao Li, Yan Lu

Abstract

An increase in hepatic triglyceride (TG) contents usually results in non-alcoholic fatty liver disease (NAFLD) and related metabolic diseases. However, the mechanisms underlying perturbations of hepatic TG homeostasis remain largely unknown. Here, we showed that MicroRNA-124 was up-regulated in the livers of C57BL/6 mice fed a short-term high-fat-diet (HFD). Adenoviral overexpression of miR-124 in C57BL/6 mice led to accumulation of excessive triglycerides and up-regulation of lipogenic genes in the liver. We further identified tribbles homolog 3 (TRB3) as a direct target of miR-124. AKT signaling, which is negatively regulated by TRB3, was enhanced by miR-124 overexpression. Moreover, restoration of TRB3 expression markedly abolished the effect of miR-124 on hepatic TG metabolism. Therefore, our findings revealed that miR-124 played a role in mediating high-fat-diet induced TG accumulation in the liver.

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