Investigation on Effects of Typical OPFRs on CREB Transcriptional Activity and Adipogenesis During Early Differentiation of Mouse Preadipocyte 3T3-L1
Organophosphate flame retardants(OPFRs)possess the capability to induce the differentiation of mouse preadipocytes 3T3-L1 into mature adipocytes,leading to a significant accumulation of triglycerides(TG)within the cells.Consequently,they might be considered as potential obesogens.Currently,the mechanism by which OPFRs induce adipogenic differentiation in 3T3-L1 cells is not well understood,particularly regarding the impact of pollu-tants during the early stage of cell differentiation(0-2 days post-induction).Cyclic AMP response element-binding protein(CREB)is a key regulator in the early stages of 3T3-L1 differentiation.To investigate the impact of OPFRs exposure on CREB transcriptional activity,this study developed a dual-luciferase reporter gene assay based on co-transfection with cAMP response element(CRE)and pGL4.73 plasmid.Further testing of 10 typical OPFRs re-vealed that,2-ethylhexyl diphenyl phosphate(EHDPP),bis(2-ethylhexyl)phenyl phosphate(BEHPP),tris(1,3-di-chloro-2-propyl)phosphate(TDCIPP),tris(2-chloroethyl)phosphate(TCEP),and tris(2-ethylhexyl)phosphate(TEHP)significantly upregulated CREB transcriptional activity in 3T3-L1 cells at a concentration of 10 μmol·L-1 during the early stages of differentiation,respectively.Moreover,the TG contents in cells exposed to six OPFRs(BEHPP,EHDPP,TEHP,TDCIPP,tris(2-chloroisopropyl)phosphate(TCIPP),TCEP)for first two days were found to significantly increase when differentiation was completed.Notably,there was a marginally significant positive correlation(P=0.07)between TG production and CREB transcriptional activity in the early stages of differentiation.The present study reveals the differential regulatory effects of OPFRs with different substituent structures in the ear-ly stages of 3T3-L1 differentiation,improves current understanding of the obesogenic effects of OPFRs,and pro-vides an important scientific basis for assessing the health risks of OPFRs.
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