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

  • Authors:
    • Yanhua Zhang
    • Yuqin Wei
    • Huan Liu
    • Yanju Guo
  • View Affiliations / Copyright

    Affiliations: School of Journalism and Communication, Wuhan Sports University, Wuhan, Hubei 430000, P.R. China, School of Physical Education and Health, Hubei Business College, Wuhan, Hubei 430000, P.R. China, College of Sports Medicine, Wuhan Sports University, Wuhan, Hubei 430000, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 146
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    Published online on: July 15, 2025
       https://doi.org/10.3892/ijmm.2025.5587
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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.
View Figures

Figure 1

Epigenetic mechanisms contribute to
the pathogenesis of metabolic dysfunction-associated fatty liver
disease. lncRNA, long non-coding RNA; miRNA or miR, microRNA; ROS,
reactive oxygen species; SRA, steroid receptor RNA activator; EV,
extracellular vesicle.

Figure 2

Physical activity exerts protective
effects on metabolic dysfunction-associated fatty liver disease by
modulating epigenetic regulatory pathways. NcRNA, non-coding
RNA.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang Y, Wei Y, Liu H and Guo Y: Protective effect of exercise on metabolic dysfunction‑associated fatty liver disease: Potential epigenetic mechanisms (Review). Int J Mol Med 56: 146, 2025.
APA
Zhang, Y., Wei, Y., Liu, H., & Guo, Y. (2025). Protective effect of exercise on metabolic dysfunction‑associated fatty liver disease: Potential epigenetic mechanisms (Review). International Journal of Molecular Medicine, 56, 146. https://doi.org/10.3892/ijmm.2025.5587
MLA
Zhang, Y., Wei, Y., Liu, H., Guo, Y."Protective effect of exercise on metabolic dysfunction‑associated fatty liver disease: Potential epigenetic mechanisms (Review)". International Journal of Molecular Medicine 56.4 (2025): 146.
Chicago
Zhang, Y., Wei, Y., Liu, H., Guo, Y."Protective effect of exercise on metabolic dysfunction‑associated fatty liver disease: Potential epigenetic mechanisms (Review)". International Journal of Molecular Medicine 56, no. 4 (2025): 146. https://doi.org/10.3892/ijmm.2025.5587
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Y, Wei Y, Liu H and Guo Y: Protective effect of exercise on metabolic dysfunction‑associated fatty liver disease: Potential epigenetic mechanisms (Review). Int J Mol Med 56: 146, 2025.
APA
Zhang, Y., Wei, Y., Liu, H., & Guo, Y. (2025). Protective effect of exercise on metabolic dysfunction‑associated fatty liver disease: Potential epigenetic mechanisms (Review). International Journal of Molecular Medicine, 56, 146. https://doi.org/10.3892/ijmm.2025.5587
MLA
Zhang, Y., Wei, Y., Liu, H., Guo, Y."Protective effect of exercise on metabolic dysfunction‑associated fatty liver disease: Potential epigenetic mechanisms (Review)". International Journal of Molecular Medicine 56.4 (2025): 146.
Chicago
Zhang, Y., Wei, Y., Liu, H., Guo, Y."Protective effect of exercise on metabolic dysfunction‑associated fatty liver disease: Potential epigenetic mechanisms (Review)". International Journal of Molecular Medicine 56, no. 4 (2025): 146. https://doi.org/10.3892/ijmm.2025.5587
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