Combined UHPLC with MALDI-MS Imaging Reveals Hepatic Lipid Metabolism Homeostasis in Tetrabromobisphenol A-Exposed Mice

The increasing exposure risks of tetrabromobisphenol A (TBBPA) have drawn much attention, owing to its widely produced and ubiquitous occurrence. Despite the potential toxicities are largely explored in vitro experiments, limited evidence exists about the fact that TBBPA induced the targeting organ effects on the metabolism. Herein, we found that TBBPA exposure for 2 weeks induced oxidative stress and lipometabolism disturbance in the liver of male ICR mice. Using the promising approach combining UHPLC-MS with MALDI imaging, 78 discrepant lipid molecules between the control and TBBPA exposure groups were simultaneously screened and identified, with spatial visualization. After the enrichment analysis, the biosynthesis of glycerophospholipid metabolism was the most distinct in the eight metabolic pathways that were involved with TBBPA in the process of liver injury, which was closely associated with hepatocyte membrane stability and lipid transport functions. Furthermore, the Q-PCR analysis and molecular docking results demonstrated that TBBPA promoted the accumulation of lipids like triglyceride (TG), DG, LPE, and LPC, as well as the deficiency of phosphatidylcholine and PE by inhibiting the key genes <i>LPCAT3 and Pcyt2</i> involved in glycerophospholipid synthesis, simultaneously enhancing the expression of <i>phosphatidylethanolamine N-methyltransferase</i> and <i>Diacylglyceryl acyltransferase 1</i>, the latter being the crucial gene for TG synthesis. This study affords novel insight into further understanding the potential effect of liver organ by TBBPA exposure.