Comparative metabolome analysis of cultured fetal and adult hepatocytes in humans

Abstract

The liver is the central organ of metabolism, but its function varies during development from fetus to adult. In this study, we comprehensively analyzed and compared metabolites in fetal and adult hepatocytes, the major parenchymal cell in the liver, from human donors. We identified 211 metabolites (116 anions and 95 cations) by capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) in the hepatocytes cultured in vitro. Principal component analysis and hierarchical clustering analysis of the relative amounts of metabolites clearly classified hepatocytes into 2 groups that were consistent with their origin, i.e., the fetus and adult. The amounts of most metabolites in the glycolysis/glyconeogenesis pathway, tricarboxylic acid cycle and urea cycle were lower in fetal hepatocytes than in adult hepatocytes. These results suggest different susceptibility of the fetal and adult liver to toxic insults affecting energy metabolism.