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.
Keywords: metabolic syndrome disease; non-alcoholic fatty liver disease; miR-146a; MEd1; mitochondria.