Metabolic Signatures in Lean MASLD: Current Insights and Future Directions

Area of Science:

• Hepatology and Metabolic Diseases

Background:

• Lean metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging entity affecting normal BMI individuals.
• It presents significant risks for cardiovascular disease, liver cancer, and mortality, comparable to obesity-associated MASLD.
• Current screening methods based on BMI are insufficient for lean MASLD diagnosis.

Purpose of the Study:

• To review current clinical and epidemiological data on lean MASLD.
• To explore its distinct pathophysiological mechanisms.
• To identify novel biomarkers and therapeutic targets.

Main Methods:

• Synthesis of evolving clinical insights and epidemiological trends.
• Delineation of unique pathophysiological mechanisms.
• Integration of evidence from metabolomics, genetics, and epigenetics.

Main Results:

• Metabolomic studies reveal specific disruptions in lipid, amino acid, and bile acid metabolism in lean MASLD.
• Gut microbiota-derived metabolites are implicated in lean MASLD pathogenesis.
• Potential biomarkers and therapeutic targets have been identified.

Conclusions:

• Lean MASLD is a distinct clinical entity requiring improved diagnostic approaches.
• Understanding its unique metabolic pathways is crucial for effective management.
• Identified biomarkers and targets offer promise for precision medicine strategies in lean MASLD.