The Complex Metabolic Interactions of Liver Tissue and Hepatic Exosome in PCOS Mice at Young and Middle Age

Polycystic ovary syndrome (PCOS) is a common age-related endocrinopathy that promotes the metabolic disorder of the liver. Growing evidence suggests that the pathophysiology of this disorder is closely associated with the interaction between the liver and its exosome. However, the underlying mechanism of the interactions remains unclear. In this study, we aimed to investigate the metabolite profiles of liver tissues and hepatic exosomes between normal (n = 11) and PCOS (n = 13) mice of young- and middle-age using gas chromatograph-mass spectrometry (GC-MS) based metabolomics analysis. Within the 145 identified metabolites, 7 and 48 metabolites were statistically different (p < 0.05, q < 0.05) in the liver tissue and exosomes, respectively, between PCOS and normal groups. The greater disparity in exosome indicated its potential to reflect the metabolic status of the liver. Based on hepatic exosome metabolome, the downregulations of glycolysis and TCA cycle were related to hepatic pathophysiology of PCOS independent of age. Fatty acids were the preferred substrates in young-age-PCOS liver while amino acids were the main substrates in middle-age-PCOS liver for the processes of gluconeogenesis. Overall, this study enables us to better understand the metabolic status of the PCOS liver at different ages, and exosome metabolomics shows its potential to gain the metabolic insights of parental cell or source organ.