Multiomics\nStudies on Metabolism Changes in Alcohol-Associated\nLiver Disease

Metabolic dysfunction in the liver represents a predominant\nfeature\nin the early stages of alcohol-associated liver disease (ALD). However,\nthe mechanisms underlying this are only partially understood. To investigate\nthe metabolic characteristics of the liver in ALD, we did a relative\nquantification of polar metabolites and lipids in the liver of mice\nwith experimental ALD using untargeted metabolomics and untargeted\nlipidomics. A total of 99 polar metabolites had significant abundance\nalterations in the livers of alcohol-fed mice. Pathway analysis revealed\nthat amino acid metabolism was the most affected by alcohol in the\nmouse liver. Metabolites involved in glycolysis and the TCA cycle\nwere decreased, while glycerol 3-phosphate (G3P) and long-chain fatty\nacids were increased. Relative quantification of lipids unveiled an\nupregulation of multiple lipid classes, suggesting that alcohol consumption\ndrives metabolism toward lipid synthesis. Results from enzyme expression\nand activity detection indicated that the decreased activity of mitochondrial\nglycerol 3-phosphate dehydrogenase contributed to the disordered metabolism.