Obesity-induced upregulation of miR-361-5p promotes hepatosteatosis through targeting Sirt1

Objective: Obesity is associated with an increased risk of many metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms remain poorly understood. Recent studies have demonstrated that MicroRNA-mediated gene silencing plays an important role in hepatic triglyceride (TG) metabolism. In the present study, we aimed to investigate the pathological function of miR-361-5p in the development of NAFLD. Methods: Expression levels of miR-361-5p was determined by quantitative real-time PCR in livers of obese mice and NAFLD patients. Liver tissues from mice with miR-361-5p overexpression or inhibition were collected and analyzed by TG contents, gene expression profile. Results: Expression of miR-361-5p was increased in the livers of two obese mouse models and NAFLD subjects. Overexpression of miR-361-5p in C57BL/6 mice led to hepatosteatosis, whereas inhibition of miR-361-5p expression in db/db mice improved TG accumulation and insulin sensitivity. Mechanistically, we identified Sirt1 as a direct target gene of miR-361-5p and re-introduction of Sirt1 largely abolished the metabolic action of miR-361-5p. Conclusions: Our results demonstrated the role of miR-361-5p in the regulation of hepatic TG homeostasis, which may provide potential therapeutic target for hepatosteatosis. (C) 2018 Elsevier Inc. All rights reserved.