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

Area of Science:

• Hepatology and Metabolic Medicine
• Exercise Physiology and Therapeutics

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex systemic metabolic disorder impacting liver, muscle, and adipose tissue.
• Current MASLD management often prioritizes weight loss, but exercise's independent metabolic benefits are increasingly recognized.

Purpose of the Study:

• To review the mechanistic and clinical evidence for exercise as a metabolic therapy in MASLD.
• To explore how exercise restores metabolic flexibility beyond body weight reduction.

Main Methods:

• Narrative review integrating mechanistic insights and clinical evidence on exercise interventions for MASLD.
• Analysis of exercise-induced pathways, including AMPK signaling, fatty acid oxidation, and myokine-mediated crosstalk.

Main Results:

• Exercise improves hepatic steatosis, insulin resistance, mitochondrial function, and inflammation in MASLD.
• Benefits are mediated by enhanced metabolic pathways and muscle-liver crosstalk, often independent of weight loss.
• Both aerobic and resistance exercise, particularly combined, show efficacy.

Conclusions:

• Exercise is a crucial therapeutic strategy for MASLD, focusing on restoring metabolic flexibility.
• Treatment strategies should shift towards metabolism-focused approaches, emphasizing exercise over sole reliance on weight reduction.
• Further research is needed to optimize personalized and sustainable exercise prescriptions for MASLD.