Lipidome Disturbances In Preadipocyte Differentiation Associated With Bisphenol A And Replacement Bisphenol S Exposure

Bisphenol A(BPA)is widely used as a chemical building block in the manufacture of polycarbonate plastics and epoxy resins for food packaging.Due to its associated health effects based on endocrine-disruption activity,restrictions have been placed on the use of BPA by regulatory organizations in recent years.In response to these restrictions and public pressure,an alternative,i.e.,bisphenol S(BPS),has become one of the major substitutes for production of “BPA-free” products.Although the relationship between BPA exposure and increased risk of obesity and diabetes has been noted,the potential influence of BPS is not fully understood.In this study,to study the comprehensive lipidome rewiring induced by BPA/BPS associated with differentiation of the 3T3-L1 cell line,we performed non-targeted lipidomics analysis using ultrahigh-performance liquid chromatography coupled to mass spectrometry(UPLC-MS).Our work aids in supplying a novel perspective into the toxicity-related metabolic response to BPA and its alternative BPS.The main work of this paper is as follows:1.Identification of lipid species in mouse preadipocyte 3T3-L1.Lipid species were identified based on the database query using the LIPID MAPS database.The MS/MS fragmentation patterns and retention behavior of lipid species were further used to confirm the identification.A total of 583 lipid species were identified,spanning 6 lipid categories of 55 sphingolipids(14 Cer,7 CerG1,34 SM),305 glycerophospholipids(17 LPC,4 LPC e/p-,87 PC,50 PC e/p-,8 LPE,32 PE,25 PE e/p-,1 LPG,28 PG,28 PI,7 PI e/p-,18 PS),173 glycerolipids(19 DG,106 TG,48 TG e/p-),35 FA,14 CL and 1 ChE.This stduy unravels the lipid composition in the cell model of mouse preadipocyte,providing a good foundation for the subsequent lipidomics evaluation.2.Lipidomics study in preadipocyte differentiation associated with BPA and replacement BPS exposure.In this study,to trace the early lipidome changes on the differentiation process,a timeseries sample set of differentiating 3T3-L1 cells was collected from day 0 to day 8.The results revealed that the comprehensive lipidome disturbance induced by either BPA or BPS exposure at different doses of 0.01,1 and 100 ?M.Although there is a larger disturbance of lipid metabolism in the magnitude for BPA exposure groups when compared with BPS groups,BPS exposure induced patterns of lipidome changes similar to those of BPA.Combined with i)the enrichment of significant changes in the lipid classes of CLs,PGs and LPGs,and ii)the definition of potential exposure biomarkers of CL(70:7)and PG(38:4),we could pinpoint the discovery in this lipidome remodeling pattern,especially the significant disturbance of cardiolipin,phosphatidylglycerol and fatty acid metabolic pathways,is implicated in the link between BPA/BPS exposure and the increased risk of insulin resistance.Then,it provides novel insights into the potential mechanism of exposure effects that BPS may also be considered a risk factor for the development of insulin resistance and associated metabolic diseases.Substitution of BPA by its structural analog BPS should be therefore performed with caution.