Identification of glycerophospholipid fatty acid remodeling by using mass spectrometry imaging in bisphenol S induced mouse liver

摘要

Bisphenol A(BPA) plays an important role in metabolic disorders. As a major alternative to BPA, it is unclear whether the exposure of bisphenol S(BPS) may result in lipidome disturbance. Using a mouse model, we investigated the effects of BPS exposure on metabolism and spatial distribution of lipids by using lipidomics analysis and matrix-assisted laser desorption/ionization(MALDI)-mass spectrometry imaging(MSI) in mouse liver tissues. Lipid metabolites displayed significant up-regulation in phosphatidylethanolamines(PE), lysophosphatidylcholines(LPC), lysophosphatidylethanolamines(LPE) and lysophosphatidylserine(LPS) as well as remarkable down-regulation in phosphatidylcholine(PC) and phosphatidylserine(PS) in mouse liver after the exposure at 100 m g BPS/kg body weight/day.The obtained results indicated that the lipidome of liver was perturbed significantly in glycerophospholipid(GP) fatty acid remodeling pathway upon the BPS exposure. We applied MSI and multivariate statistical analysis to evaluate the abundance variation of lipid markers in BPS-treated liver sections and to compare with the analytical results from olive oil-treated liver sections. Differential structural lipids with up-regulated PE(20:1/20:4), LPC(20:4), LPE(20:4), LPS(33:4) and down-regulated PC(20:4/22:6)and PS(18:0/22:6), which were related to GP fatty acid remodeling, changed and co-localized in the liver sections. To explore the cause of variation of lipid abundance, expression of enzymes that regulate biosynthesis and metabolism of fatty acid in liver tissues were analyzed. Consistent with the results of liver lipidome and spatial distribution, a decrease in hepatic expression of LPC acyltransferase 1(LPCAT1),LPCAT2 and LPS acyltransferase and an increase expression of LPCAT3, LPCAT4, LPE acyltransferase 1(LPEAT1), LPEAT2 and phospholipase A2 s were observed in GP fatty acid remodeling pathway. Our results demonstrated that exposure to BPS could induce the GP fatty acid remodeling, which might be useful in toxicity evaluation for bisphenols-induced hepatic diseases.