Aerobic exercise improves hepatic steatosis by modulating miR-34a-mediated PPARα/SIRT1-AMPK signaling pathway

Abstract

Abstract The role of aerobic exercise in preventing and ameliorating non-alcoholic fatty liver disease (NAFLD)has been widely demonstrated. MicroRNA-34a (MiR-34a) , a small non-coding RNA that regulates gene expression, has received much attention for its essential role in the progression of metabolic liver disease. However, it is unclear whether exercise can prevent and ameliorate hepatic lipid degeneration by targeting miR-34a and its underlying molecular mechanisms. In this study, normal or high-fat diet -induced male C57BL/6J mice underwent an 8-week running program (6 days/week, 18 m/min, 50 min, 6% incline) or remained sedentary. Histomorphometric examination and biochemical analysis were performed to evaluate intrahepatic lipid deposition. Adeno-associated viral vectors were injected into mice to construct miR-34a liver-specific overexpression mice. Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression of genes and proteins related to lipid metabolism in the liver. After exercise intervention, the liver weight/body weight, liver TG, and HE of mice in the High-fat diet with aerobic exercise group (HCE) indicated significant improvement in hepatic steatosis, and mir-34a levels were significantly suppressed. This study identified aerobic exercise improves hepatic lipid degeneration by increasing the expression of its target genes PPARα and SIRT1 through mir-34a and activating the expression of AMPK and changes in genes related to lipid metabolism downstream of the PPARα/SIRT1-AMPK pathway.