Exercise Combined with Dietary Switch Improves MASLD by Suppressing Hepatic MOGAT1 and Modulating Metabolic Stress Pathways in HFD-Fed Mice

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a progressive liver disorder that can lead to irreversible hepatic damage when chronic inflammation and fibrosis develop. Exercise and dietary switch have been suggested as effective strategies for improving MASLD. However, their effects in severe MASLD induced by long-term obesity remain unclear. Therefore, this study investigated the combined effects of exercise and dietary switch in a mouse model of severe MASLD induced by long-term high-fat diet feeding. The combined intervention significantly reduced body weight and improved glucose tolerance compared with either intervention alone. In addition, exercise combined with dietary switch was associated with reduced expression of lipogenesis-related proteins, including monoacylglycerol O-acyltransferase 1. The intervention was also accompanied by alterations in proteins related to mitochondrial regulation, antioxidant defense, and autophagy. Histological analysis further demonstrated improvements in hepatic steatosis and MASLD activity scores. In mice with severe MASLD, the combination of exercise and dietary switch was more effective than either intervention alone in improving hepatic lipid accumulation and molecular markers associated with MASLD.