MiR‐22 modulates the expression of lipogenesis‐related genes and promotes hepatic steatosis in vitro

We observed that miR‐22 can promote hepatic steatosis. Conversely, steatosis was alleviated after inhibition of miR‐22, indicating that miR‐22 is involved in fat deposition. Furthermore, miR‐22 was validated to have effects on downstream lipid metabolism‐related genes, revealing the pathways through which miR‐22 regulates lipid metabolism. Therefore, miR‐22 may be a promising target for the treatment of NAFLD and obesity. Nonalcoholic fatty liver disease (NAFLD) is highly correlated with obesity, and lifestyle changes to reduce weight remain the main therapeutic approach. The noncoding RNA miR‐22 has previously been reported to be highly abundant in the sera of NAFLD patients. In addition, miR‐22 directly targets peroxisome proliferative‐activated receptor, Pgc‐1α, peroxisome proliferator‐activated receptor α, and sirtuin 1 (Sirt1), which are important factors involved in fatty acid metabolism. Given that miR‐22 directly targets genes involved in the control of metabolism and obesity, we investigated whether miR‐22 contributes to metabolic alterations induced by obesity. We observed increased expression of miR‐22, decreased expression of Sirt1, and alterations in the expression of adipogenesis‐related genes in a mouse model of obesity and a human hepatocyte cell line. We identified that miR‐22 and the 3′‐UTR of Sirt1 are complementary. Mutation of the complementary fragment abolishes the ability of miR‐22 to regulate the Sirt1 gene. Furthermore, treatment of hepatic steatosis cells with miR‐22 mimics or inhibitors showed that miR‐22 can promote hepatic steatosis, and miR‐22 inhibitors effectively reduced triglyceride levels without affecting cell activity. Finally, we validated that miR‐22 has similar effects on downstream lipid metabolism‐related genes. Our data reveal the pathways and mechanisms through which miR‐22 regulates lipid metabolism and suggest that miR‐22 inhibitors may have potential as candidate drugs for NAFLD and obesity.