Polycystic ovary syndrome (PCOS) is a complex reproductive, endocrine, and metabolic disorder in reproductive-age women. In order to explore the active metabolites of brown adipose tissue (BAT) transplantation in improving the reproductive and metabolic phenotypes in a PCOS rat model, the metabolites in the recipient's BAT were explored using the liquid chromatography-mass spectrometry technique. In total, 9 upregulated and 13 downregulated metabolites were identified. They were roughly categorized into 12 distinct classes, mainly including glycerophosphoinositols, glycerophosphocholines, and sphingolipids. Ingenuity pathway analysis predicted that these differentially metabolites mainly target the PI3K/AKT, MAPK, and Wnt signaling pathways, which are closely associated with PCOS. Furthermore, one of these differential metabolites, sphingosine belonging to sphingolipids, was randomly selected for further experiments on a human granulosa-like tumor cell line (KGN). It significantly accelerated the apoptosis of KGN cells induced by dihydrotestosterone. Based on these findings, we speculated that metabolome changes are an important process for BAT transplantation in improving PCOS. It might be a novel therapeutic target for PCOS treatment.
基金:
Scientific Research Project of Shanghai Municipal Health Commission [20194Y007]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [82001508, 81903006]; Natural Science Foundation of Jiangsu ProvinceNatural Science Foundation of Jiangsu Province [BK20181089]; Shanghai Changning District Science and Technology Commission Project [CNKW2018Y06]