Skeletal muscle alterations in metabolic dysfunction-associated steatotic liver disease: A critical review of diagnostic, mechanistic, and therapeutic intersections

Abstract

Metabolic dysfunction-associated steatotic liver disease is increasingly understood to be closely linked with skeletal muscle alterations, such as sarcopenia, myosteatosis, and metabolic dysregulation, which play a key role in its pathogenesis and progression. Recent literature, including an article by Isakov, highlights the bidirectional interactions between muscle and liver, underscoring shared mechanisms such as insulin resistance, inflammation, and myokine imbalance. This letter reflects on key findings from the review, noting strengths such as its integration of mechanistic insights, discussion of emerging biomarkers, and emphasis on lifestyle and pharmacological interventions. It also identifies areas for further development, including standardization of diagnostic criteria and more rigorous evaluation of translational data. As muscle health gains prominence in metabolic dysfunction-associated steatotic liver disease research, multidisciplinary strategies that target both hepatic and muscular systems may offer more effective avenues for prevention and treatment.

Keywords: Metabolic dysfunction-associated steatotic liver disease; Skeletal muscle alterations; Sarcopenia; Myosteatosis; Muscle metabolism; Physical activity; Glucagon-like peptide-1 receptor agonists

Core Tip: Skeletal muscle alterations, such as sarcopenia, myosteatosis, and metabolic dysregulation, are increasingly common in pathogenesis and progression of metabolic dysfunction-associated steatotic liver disease. Underlying mechanisms, including insulin resistance, inflammation, and myokine imbalance, along with emerging biomarkers offer opportunities to study lifestyle and pharmacological interventions such as glucagon-like peptide-1 agonists. Further development must build on gaps in current literature, standardize diagnostic criteria and evaluate translational data for clinical applicability.