Protective effect of exercise on metabolic dysfunction‑associated fatty liver disease: Potential epigenetic mechanisms (Review).

Abstract

Metabolic dysfunction‑associated fatty liver disease (MAFLD) is the most prevalent cause of chronic liver disease worldwide and poses a major health burden that is closely linked to obesity, insulin resistance and type 2 diabetes. While extensive research has elucidated key molecular drivers, no pharmacological therapies have been approved. Emerging evidence highlights the transformative role of physical exercise as a potent nonpharmacological intervention capable of inducing durable metabolic improvements. Epigenetic remodeling, which encompasses DNA methylation, histone modifications and non‑coding RNA regulation, has been increasingly recognized as a key mechanism driving these long‑lasting effects. Aberrant epigenetic modifications disrupt hepatic lipid metabolism, mitochondrial function, autophagy, inflammation and fibrosis progression, thereby driving MAFLD pathogenesis. The present review comprehensively covers the current knowledge on epigenetic mechanisms implicated in MAFLD and systematically assesses how distinct exercise modalities reshape these epigenetic landscapes to restore hepatic metabolic homeostasis. Understanding the epigenetic underpinnings of exercise‑induced hepatic protection offers a promising avenue for advancing personalized interventions and novel therapeutics for MAFLD.