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

MicroRNA-34a (miR-34a) was closely associated with liver steatosis. However, the link between changes in miR-34a and the progression of liver steatosis remained unclear. In the work, sixty mice were randomly and equally selected into six groups: normal control group (NC), normal exercise group (NE), high-fat diet group (HFD), high-fat diet plus exercise group (HFE), miR-34a overexpression group (OE), and miR-34a overexpression plus exercise group (OEE). Live morphology showed that treadmill exercise intervention for 8 weeks reduced high-fat diet-induced liver steatosis in mice. 8-week treadmill exercise directly decreased mir-34a expression of mice in HFD group, confirmed in OE group. More, treadmill exercise enhanced the expression of PPARα and SIRT1, thereby affecting the downstream hepatic steatosis-associated target genes, including CPT1, CPT2, SLC27A4, SLC27A1, in addition to activating the expression of the central metabolic sensor AMPK. Following aerobic exercise intervention, miR-34a was upregulated, thereby affecting the expression of genes associated with hepatic steatosis, and this mechanism was confirmed in miR-34a overexpression mice. This study contributed to our understanding of the pathogenesis of hepatic steatosis and may provide new therapeutic approaches.