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Metabonomics reveals bisphenol A affects fatty acid and glucose metabolism through activation of LXR in the liver of male mice

Ji, Hainan, Song, Naining, Ren, Juan, Li, Wentao, Xu, Baoliang, Li, Haishan, Shen, Guolin
The Science of the total environment 2020 v.703 pp. 134681
bioinformatics, bisphenol A, computer simulation, computer software, endocrine-disrupting chemicals, enzyme activity, epoxides, fatty acids, gene expression, glucose, histopathology, hypoglycemia, liver, males, mass spectrometry, messenger RNA, metabolism, metabolomics, mice, neoplasms, plastics, reproductive system, resins, tricarboxylic acid cycle
Bisphenol-A (BPA) is a representative environmental endocrine disrupting chemical that is widely used in the production of polycarbonate plastics and epoxy resins. Many studies have confirmed BPA to be closely associated with metabolic diseases, reproductive system diseases, and sex hormone-dependent cancers. In this study, we aimed to systematically elucidate the molecular action of BPA on liver fatty acid and glucose metabolism and the reasons for BPA-induced hypoglycemia through a metabonomics approach. C57BL/6 mice were orally treated with BPA (1, 10, 50, 250 μg/kg) for 35 days and the liver metabonomics and histopathology, molecular docking, mRNA expression levels and activities of enzymes were analyzed. Based on the high-resolution mass spectrometry (MS) for metabonomics and on various software and bioinformatic analysis methods, we found that BPA could affect fatty acid and glucose metabolism, block the TCA cycle, and BPA also regulated the nuclear receptor LXR caused hypoglycemia, thereby affecting the normal metabolic functions of the liver.