Effects Of Endurance Exercise On Non-alcoholic Fatty Liver Disease In Mouse

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is caused by the accumulation of triglycerides in hepatocytes and is exacerbated by a sedentary lifestyle. NAFLD now affects over 30% of the United States population, making it a growing health concern. Although there is currently no cure for NAFLD, endurance exercise is known to have restorative effects on the liver and can reverse disease progression, though the mechanism behind this improvement remains unknown. The present study investigated whether endurance exercise positively influences autophagy and lipid metabolism and explored the role of specific enzymes associated with ferroptosis as a potential factor in the progression of NAFLD. METHODS: Seven-week-old female C57BL/6 J mice (n = 33) were randomly divided into three groups: the control group (CON, n = 11), the high-fat diet + streptozotocin group (HFD/STZ, n = 11), and the high-fat diet + st2reptozotocin + exercise group (HFD/STZ + EXE, n = 11). After eight weeks of HFD, the mice assigned to the STZ groups received a single intraperitoneal injection of 100 mg/kg of STZ to induce type 2 diabetes. The HFD/STZ + EXE group followed a treadmill running exercise (15 m/min for 60 minutes per day, 5 days per week for 15 weeks). Western blot for protein analyses and histology for lipid droplet measurement were used. RESULTS: The present study revealed that exercise training decreased de novo lipogenesis by downregulating Diacylglycerol acyltransferase, but an enzyme level involved in fatty acid metabolism (e.g., Acyl-CoA Synthetase Long-Chain Family Member 1) remained the same. Exercise also showed a restorative effect on autophagy, indicated by decreased p62 and increased LAMP2 levels. Finally, exercise promoted anti-ferroptosis effects, evidenced by increased antioxidant enzymes such heme oxygenase-1 alongside GPX4 and catalase, which detoxify hydrogen peroxide. CONCLUSIONS: Our study suggests that exercise-induced repression of novo lipogenesis may contribute to ameliorating NAFLD. Moreover, the restoration of autophagy flux and improvement in antioxidant activity may be potential mechanisms of exercise-induced protection against NAFLD.