Lipidomics and proteomics in MASLD: reading the molecular script toward precision therapeutics

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a multisystem disorder characterized by complex metabolic, inflammatory, and fibrogenic interactions. Advances in lipidomics and proteomics have substantially refined understanding of MASLD pathophysiology by revealing how qualitative alterations in lipid species and dynamic protein signaling networks contribute to disease initiation and progression. Bioactive lipids, including ceramides and free cholesterol, promote lipotoxicity, mitochondrial dysfunction, inflammasome activation, and fibrosis, while proteomic analyses have identified key pathways involved in inflammation, cellular senescence, and hepatic stellate cell activation. Emerging translational evidence further suggests that modern pharmacological agents may modulate these molecular signatures beyond their metabolic effects. Integrating lipidomic and proteomic data may therefore facilitate improved disease stratification, biomarker discovery, and the development of mechanism-based therapeutic strategies, supporting a transition toward precision medicine in MASLD.