MiR‑146a improves hepatic lipid and glucose metabolism by targeting MED1.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Increasing evidence has shown that microRNAs (miRNAs) play a vital role in the progression of NAFLD. The aim of the present study was to examine the expression level and roles of miR-146a in fatty liver of high-fat diet (HFD) and ob/ob mice and fatty acid-treated hepatic cells using RT-qPCR and western blot analysis. The results showed that the expression of miR-146a was significantly decreased in the livers of high-fat diet (HFD) and ob/ob mice and free fatty acid-stimulated cells by RT-qPCR. Overexpression of hepatic miR-146a improved glucose and insulin tolerance as well as lipid accumulation in the liver by promoting the oxidative metabolism of fatty acids. In addition, the overexpression of miR-146a increased the amount of mitochondria and promoted mitochondrial respiration in hepatocytes. Similarly, inhibition of miR-146a expression levels significantly reduced mitochondrial numbers in AML12 cells as well as the expression of mitochondrial respiration related genes. Additionally, MED1 was a direct target of miR-146a and restoring MED1 abolished the metabolic effects of miR-146a on lipid metabolism and mitochondrial function. Therefore, results of the present study identified a novel function of miR-146a in glucose and lipid metabolism in targeting MED1, suggesting that miR-146a serves as a potential therapeutic target for metabolic syndrome disease.