Metabolic Signatures in Lean MASLD: Current Insights and Future Directions




Babu, Ambrin Farizah

PublisherMDPI AG

2025

Metabolites

METABOLITES

583

15

9

2218-1989

DOIhttps://doi.org/10.3390/metabo15090583

https://doi.org/10.3390/metabo15090583

https://research.utu.fi/converis/portal/detail/Publication/504540300



Lean metabolic dysfunction-associated steatotic liver disease (lean MASLD) challenges longstanding views that link hepatic steatosis primarily to obesity. Emerging as a distinct and under-recognized clinical entity, lean MASLD affects individuals with a normal body mass index (BMI), yet carries risks of cardiovascular disease, hepatocellular carcinoma, and liver-related mortality comparable to obesity-associated MASLD. The absence of overt metabolic dysfunction complicates diagnosis, revealing critical limitations in current screening frameworks centered on BMI. This review synthesizes evolving clinical insights and epidemiological trends in lean MASLD, and delineates its unique pathophysiological mechanisms. Recent advances in metabolomics have uncovered disease-specific disruptions in lipid and amino acid metabolism, bile acid signaling, and gut microbiota-derived metabolites. By integrating evidence from metabolic, genetic, and epigenetic domains, we identified promising biomarkers, and therapeutic targets that may support earlier detection and precision-guided treatment strategies.


Babu AF received a working grant from the Finnish Cultural Foundation (grant no. 00210224), and Jenny and Antti Wihuri Foundation (grant no. 230029).


Last updated on 2025-09-10 at 11:39