A Multi-Omics Integration Analysis Reveals That <i>Mori Fructus</i> Polysaccharide Ameliorates Liver Injury via Regulating Liver Metabolic Function Through Inhibiting Lipid Metabolism, Enhancing Glycolysis, and Promoting Amino Acid Utilization

Alcohol-associated liver disease (ALD) is a prevalent chronic liver disease worldwide, with unclear pathogenesis and limited effective treatments. <i>Mori Fructus</i> polysaccharide (MFP-1) exhibits good therapeutic potential for ALD, but its mechanism remains unclear. This study aims to elucidate how MFP-1 mitigates ALD. An integrated multi-omics approach, encompassing quantitative proteomics, metabolomics, and lipidomics, was employed to systematically characterize the hepatic response to MFP-1 in ALD. MFP-1 coordinates metabolic reprogramming by regulating fatty acid synthesis and β-oxidation. It also enhances branched-chain amino acid catabolism via the 2-oxocarboxylic acid pathway, optimizing energy generation and amino acid utilization. MFP-1 protects against ALD by simultaneously targeting multiple metabolic vulnerabilities. These findings elucidate the mechanistic basis of MFP-1's hepatoprotective effects and highlight its potential for improving ALD.