Exercise as a Metabolic Therapy for MASLD: Beyond Weight Loss Toward Sustainable Exercise Strategies

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a systemic metabolic disorder characterized by impaired metabolic flexibility involving the liver, skeletal muscle, and adipose tissue. Although weight loss has traditionally been emphasized in its management, emerging evidence suggests that exercise exerts therapeutic effects beyond body weight reduction. This narrative review aims to examine exercise as a metabolic therapy for MASLD by integrating mechanistic insights and clinical evidence. Exercise improves hepatic steatosis, insulin resistance, mitochondrial function, and inflammatory signaling through interconnected pathways, including activation of AMPK-related signaling, enhanced fatty acid oxidation, and muscle-liver crosstalk mediated by myokines. Importantly, these benefits can occur independently of weight loss, supporting a shift from weight-centered to metabolism-focused treatment strategies. Both aerobic and resistance exercise demonstrate efficacy, with combined approaches providing complementary benefits. In conclusion, exercise should be considered a central therapeutic strategy for MASLD by restoring metabolic flexibility rather than solely promoting weight reduction. Future research should focus on optimizing individualized and sustainable exercise prescriptions to enhance long-term clinical outcomes.