A lipidomic approach to bisphenol F-induced non-alcoholic fatty liver disease-like changes: altered lipid components in a murine model

Abstract

Bisphenol A (BPA), a typical environmental endocrine disruptor, is an "obesogen" that can induce lipid accumulation in the liver. Highly similar in structure to BPA, bisphenol F (BPF) is becoming the dominant BPA substitute on the market, which attracts more and more attention due to its potential adverse effects. Recently, BPF exposure is found to cause non-alcoholic fatty liver disease (NAFLD)-like changes; however, the underlying toxic effects remain poorly understood. Therefore, in the current study, we focused on BPF-mediated lipid homeostasis, especially the alterations of lipid components and metabolism. In human serum, the BPF levels in healthy controls and NAFLD patients were assessed by ELISA, and BPF-induced disturbance of lipid metabolism was evaluated in mouse model via non-targeted lipomic methods with ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. It suggested that BPF exposure was positively correlated with NAFLD severity and triglyceride level in patients. Based on the relationships, lipid metabolites were assessed in mouse livers between control and BPF-treated group, and it revealed that twenty-six lipid metabolites (including phospholipids, sphingolipids, and glycerides) were significantly changed in mouse livers. Phosphatidylcholine, phosphatidylethanolamine, and diglyceryl ester levels were lower than those in the control mice; hexose ceramide content in sphingolipids markedly increased in BPF-treated mouse livers. Noteworthily, the glycerophospholipid metabolic pathway was found to be the most pronounced in BPF-induced disturbance of lipid metabolism. Therefore, the current study, for the first time, is deciphering the BPF-induced lipid metabolic disturbance, which may provide novel intervention strategies for BPF-induced NAFLD-like changes.

Keywords: Bisphenol F; Lipidomics; Non-alcoholic fatty liver disease; Non-targeted detection; Triple TOF 5600+ LC-QTOF.