Comparable hepatocellular metabolomic signatures under glucose and palmitic acid treatment relative to butyrate in relation to metabolic dysfunction-associated fatty liver disease

Among the dietary factors, glucose, and fatty acids are known to trigger fatty liver disease, while butyrate attenuates steatosis. To decipher the hepatocellular altered metabolome under nutrient perturbation relevant to fatty liver disease. HepG2 cells were cultured under the influence of sub-lethal doses of glucose, palmitic acid (PA), and butyrate. Following the treatment, intracellular metabolites were extracted and derivatized for GCMS analysis. Chemical class enrichment, metabolic pathway analysis, and metabolomic interactome analysis were undertaken. Glucose, PA and butyrate caused loss of cell viability at 160 mM, 1600 µM, and 40 mM concentration, respectively. A total of 39, 47, 52, and 51 metabolites were identified in control, glucose, PA, and butyrate, respectively, among which 2-ethylhexanoic acid in control and 2-ethylhexan-1-ol in glucose, PA and butyrate were the most abundant metabolites. Pathways related to the mitochondrial electron transport chain were highly enriched in glucose and PA treatments, leading to increased free radicals. The metabolites identified under glucose and PA treatment were linked to the metabolomic markers of metabolic liver diseases. Our data showed that the hepatocellular metabolome of HepG2 cells under glucose and PA treatment is closely related, while the metabolome and pathways associated with butyrate treatment are associated with energy metabolism and alleviation of fatty liver.