A pan-tissue multi-omics resource atlas of coordinated immune, metabolic, and fibrotic alterations in diet-induced...

Metabolic dysfunction-associated steatohepatitis (MASH) is a systemic metabolic disease involving coordinated alterations across multiple organs. Here, we established a diet-induced murine model of MASH and performed integrated transcriptomic, proteomic, and metabolomic profiling across seven metabolic tissues and the circulation, encompassing the liver, white and brown adipose tissues, skeletal muscle, gallbladder, pancreas, and plasma. Multi-omics analyses identified coordinated molecular changes across tissues, including altered immune, metabolic, and fibrotic programs. Metabolomic profiling further revealed widespread changes in lipid and amino acid metabolism, together with altered gut-derived metabolites in tissues and plasma. Several candidates showing concordant transcript and protein changes in mouse tissues, particularly in the liver, were also supported by independent human liver datasets. This study provides a multi-tissue, multi-omics resource for diet-induced MASH and offers a framework for investigating molecular interactions among metabolically connected organs.