Effect of miR-34a in regulating steatosis by targeting PPAR? expression in nonalcoholic fatty liver disease.

ABSTRACT: MicroRNA-34a (miR-34a) is thought to be involved in nonalcoholic fatty liver disease (NAFLD). However, the association between altered expression of miR-34a and the pathophysiological features of NAFLD remains unclear. Here, we investigated the mechanisms by which miR-34a influences NAFLD through the PPAR?-related pathway. Real-time quantitative PCR, western blotting and other assays kit were used to investigate the expression and function of miR-34a in an NAFLD model. Cultured cells transfected with miR-34a inhibitor and C57BL/6 mice injected with the miR-34a inhibitor through vein tail were conducted for the effects of miR-34a on its target. MiR-34a levels were significantly upregulated in steatosis-induced hepatocytes and in liver tissues of high-fat diet-fed mice. The upregulation of miR-34a resulted in the downregulation of hepatic PPAR? and SIRT1 that are the direct targets of miR-34a. Silencing miR-34a led to an initially increased expression of PPAR?, SIRT1 and PPAR?'s downstream genes. Activation of the central metabolic sensor AMPK was also increased. The miR-34a inhibitor suppressed lipid accumulation and improved the degree of steatosis. Taken together, our data indicated that decreased expression of miR-34a potentially contributes to altered lipid metabolism in NAFLD. Downregulation of miR-34a may be a therapeutic strategy against NAFLD by regulating its target PPAR? and SIRT1.

SUBMITTER: Ding J 

PROVIDER: S-EPMC4557122 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature