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

Nonalcoholic 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 miR146a in fatty liver of highfat diet (HFD) and ob/ob mice and fatty acidtreated hepatic cells using RTqPCR and western blot analysis. The results showed that the expression of miR146a was significantly decreased in the livers of highfat diet (HFD) and ob/ob mice and free fatty acidstimulated cells by RTqPCR. Overexpression of hepatic miR146a 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 miR146a increased the amount of mitochondria and promoted mitochondrial respiration in hepatocytes. Similarly, inhibition of miR146a 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 miR146a and restoring MED1 abolished the metabolic effects of miR146a on lipid metabolism and mitochondrial function. Therefore, results of the present study identified a novel function of miR146a in glucose and lipid metabolism in targeting MED1, suggesting that miR146a serves as a potential therapeutic target for metabolic syndrome disease.