Restoring Mitochondrial Homeostasis: Therapeutic Strategies for Metabolic Dysfunction-Associated Fatty Liver Disease

TL;DR

This paper reviews how restoring mitochondrial function could help treat fatty liver disease caused by metabolic dysfunction.

Contribution

The paper highlights new therapeutic strategies targeting mitochondrial biogenesis for MAFLD treatment.

Findings

Mitochondrial dysfunction contributes significantly to MAFLD progression.

Compounds promoting mitochondrial biogenesis show promise in preclinical studies.

Targeting pathways like PGC-1α and SIRT1 may offer effective MAFLD therapies.

Abstract

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become the most prevalent chronic liver disorder worldwide, driven by metabolic dysfunction, excessive lipid accumulation, and progressive hepatocellular injury. A growing body of evidence identifies mitochondrial impairment as a central contributor to MAFLD pathogenesis and disease progression. Reduced oxidative capacity, elevated reactive oxygen species, and accumulation of dysfunctional mitochondria collectively exacerbate steatosis, inflammation, and metabolic inflexibility. In recent years, therapeutic strategies aimed at restoring mitochondrial homeostasis have gained considerable attention, with particular focus on agents capable of inducing mitochondrial biogenesis through pathways involving PGC-1α, AMPK, SIRT1, and mTOR. This review synthesizes current knowledge on mitochondrial dysfunction in MAFLD and highlights emerging compounds that ameliorate disease phenotypes by enhancing mitochondrial biogenesis. By examining their mechanisms of action and preclinical efficacy, we underscore the therapeutic potential of targeting mitochondrial quality-control pathways, mainly mitochondrial biogenesis, as a promising avenue for mitigating MAFLD progression.

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