Altered Mitochondrial Function in MASLD: Key Features and Promising Therapeutic Approaches

Area of Science:

• Hepatology and Metabolic Disorders
• Mitochondrial Biology and Disease

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD), previously nonalcoholic fatty liver disease (NAFLD), is a spectrum of liver conditions with increasing global prevalence, particularly in patients with metabolic syndrome.
• MASLD pathogenesis involves complex factors including metabolic dysregulation, inflammation, oxidative stress, genetic predispositions, and critically, mitochondrial dysfunction.

Purpose of the Study:

• To elucidate the pivotal role of mitochondrial dysfunction in the progression of MASLD.
• To explore novel and existing therapeutic strategies targeting mitochondrial function for MASLD and metabolic-associated steatohepatitis (MASH) treatment.

Main Methods:

• Review of recent scientific literature focusing on MASLD pathogenesis and mitochondrial dysfunction.
• Analysis of therapeutic interventions, including lifestyle modifications, pharmacological agents, and emerging strategies like gene editing.

Main Results:

• Mitochondrial dysfunction is a key driver in the progression of MASLD from steatosis to more severe forms like MASH.
• Therapeutic enhancement of mitochondrial function, alongside lifestyle changes, shows promise for MASLD management.
• FDA approval of resmetirom for MASH with fibrosis signifies a therapeutic advancement.

Conclusions:

• A deeper understanding of MASLD-related mitochondrial dysfunction is crucial for developing effective treatments.
• Innovative approaches, including drug repurposing and targeting novel pathways, are needed to address the growing global burden of MASLD.
• Combined strategies involving lifestyle interventions and targeted therapies hold potential for improved patient outcomes.