Integration of Metabolomics, Lipidomics, and Proteomics Reveals the Metabolic Characterization of Nonalcoholic Steatohepatitis

Metabolic dysfunction is associated with nonalcoholicsteatohepatitis(NASH) development. However, omics studies investigating metabolicchanges in NASH patients are limited. In this study, metabolomicsand lipidomics in plasma, as well as proteomics in the liver, wereperformed to characterize the metabolic profiles of NASH patients.Moreover, the accumulation of bile acids (BAs) in NASH patients promptedus to investigate the protective effect of cholestyramine on NASH.The liver expression of essential proteins involved in FA transportand lipid droplets was significantly elevated in patients with NASH.Furthermore, we observed a distinct lipidomic remodeling in patientswith NASH. We also report a novel finding suggesting an increase inthe expression of critical proteins responsible for glycolysis andthe level of glycolytic output (pyruvic acid) in patients with NASH.Furthermore, the accumulation of branched chain amino acids, aromaticamino acids, purines, and BAs was observed in NASH patients. Similarly,a dramatic metabolic disorder was also observed in a NASH mouse model.Cholestyramine not only significantly alleviated liver steatosis andfibrosis but also reversed NASH-induced accumulation of BAs and steroidhormones. In conclusion, NASH patients were characterized by perturbationsin FA uptake, lipid droplet formation, glycolysis, and accumulationof BAs and other metabolites.