The Role of Mitochondrial Dynamics in Metabolic Dysfunction-Associated Steatotic Liver Disease and the Regulatory Mechanisms of Exercise Intervention: A Systematic Review of Preclinical Studies

TL;DR

This review explores how exercise can improve liver mitochondrial function in metabolic liver disease by influencing fusion, fission, and mass control.

Contribution

The paper systematically reviews preclinical evidence on modality-specific and intensity-dependent effects of exercise on mitochondrial dynamics in MASLD.

Findings

MASLD is associated with a 'pro-fission' mitochondrial phenotype.

Exercise, especially MICT and HIIT, reverses mitochondrial dysfunction via pro-fusion and anti-fission effects.

Resistance exercise shows distinct effects on fission and fusion regulation.

Abstract

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) involves dysregulated mitochondrial dynamics. This review systematically integrates the specific mechanisms by which exercise modulates mitochondrial fusion, fission, and mass control in the liver within MASLD and metabolic dysfunction-associated steatohepatitis (MASH) models. Methods: A comprehensive search of PubMed and Web of Science identified 11 animal studies investigating exercise and mitochondrial dynamics markers. Results: MASLD generally exhibited a “pro-fission” phenotype. Exercise, particularly moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT), reversed these alterations via “pro-fusion, anti-fission” effects and restored biogenesis and mitophagy. Crucially, effects appeared to be “modality-specific” and “intensity-dependent.” Current evidence suggests that reversing severe fission and restoring inner-membrane may require a specific “intensity threshold,” with voluntary wheel running showing limited efficacy in steatohepatitis. Notably, resistance exercise seemed to display a distinct profile, effectively curbing fission but diverging in fusion/biogenesis regulation. Conclusions: Synthesizing preclinical evidence, this review suggests that exercise ameliorates hepatic mitochondrial dysregulation in MASLD and appears to exhibit characteristics of “modality specificity” and “intensity dependence.” Specifically, an “intensity threshold” may be critical for profound structural remodeling, while resistance exercise exhibits a distinct regulatory profile. Future long-term clinical trials are warranted to validate these animal-derived findings and develop stage-specific “precision exercise prescriptions” for patients.

Figures