Identification of mechanisms of action of bisphenol A-induced human preadipocyte differentiation by transcriptional profiling

Abstract

Objective: Exposure to the endocrine-disrupting chemical bisphenol A (BPA) is correlated with obesity and adipogenesis of human preadipocytes. However, the mechanism of action of BPA-induced human adipogenesis remains to be determined. Methods: Primary human preadipocytes were differentiated in the presence of 50 μM BPA or 1 μM dexamethasone (DEX) for 48 hours. Potential mechanisms of BPA-induced adipogenesis were evaluated using gene expression microarray analysis. Results: Microarray analysis revealed 373 differentially expressed genes following BPA treatment, including upregulation of sterol regulatory element binding factor 1 (SREBF1), a key regulator of lipid metabolism. For DEX-treated preadipocytes, 2167 genes were differentially expressed, including upregulation of the adipogenic marker lipoprotein lipase. Ingenuity Pathway Analysis was used to identify functional annotations of the gene expression changes associated with response to BPA and DEX. BPA exposure was associated with expression changes in the genes involved in triacylglycerol accumulation while DEX was linked to triacylglycerol and fatty acid metabolism. The analysis also revealed enrichment of genes following BPA exposure in the thyroid-receptor/retinoic X receptor (TR/RXR) and mammalian target of rapamycin (mTOR) signaling pathways. Conclusions: Our data suggest that potential mechanisms of action of BPA-induced adipogenesis involve SREBF1, the TR/RXR, and the mTOR pathways.