Early-life exposure to bisphenol A induces dysregulation of lipid homeostasis by the upregulation of SCD1 in male mice

Exposure of Bisphenol A (BPA) is closely associated with an increased prevalence of obesity-related metabolic syndrome. However, the potential mechanism of BPA-induced adipogenesis remains to be fully elucidated. Herein, potential mechanisms of BPA-induced adipogenesis in 3T3-L1 preadipocytes were evaluated using RNASeq. Then, using an early-life BPA exposure model, we further evaluated the effects of BPA exposure on lipid and glucose homeostasis. The results showed that lipid content in 3T3-L1 adipocytes was significantly increased after BPA exposure (p < 0.01) and male C57BL/6 mice with the dose of 500 mu g/kg/day BPA by once-a-day oral administration for 8 weeks displayed a NAFLD-like phenotype. RNA-Seq analysis of preadipocytes showed that BPA exposure affected multiple biological processes including glycosphingolipid biosynthesis, regulation of lipolysis in adipocytes, PPAR signaling pathway and fatty acid metabolism. The dysregulation in a series of genes of mice was associated to de novo lipogenesis and lipid transport, which was linked to obesity. Importantly, we also found a significant expression increase of stearoyl-CoA desaturase 1 (SCD1) and a significant decrease of apolipoprotein D (APOD) in both fat (p < 0.01) and livers (p < 0.01) of male mice. Besides, the dysregulation of pro-inflammatory genes (TNF-alpha,IL-6 and SAA3) showed that BPA exposure promoted progression of hepatic inflammation. In conclusion, this study elucidated a novel mechanism in which obesity associated with BPA exposure by targeting SCD1. Exposure to BPA should be carefully examined in the chronic liver metabolic diseases.

Automated summary

Exposure to Bisphenol A (BPA) is associated with an increased prevalence of obesity-related metabolic syndrome. This study investigated the mechanisms of BPA-induced adipogenesis in preadipocytes and the effects of BPA exposure on lipid and glucose homeostasis using cell and animal models. The results showed that BPA exposure increased lipid content in adipocytes and caused a NAFLD-like phenotype in mice. RNA-Seq analysis revealed dysregulation in multiple biological processes, such as lipid metabolism and inflammation. Importantly, abnormal expression of SCD1 and APOD was found in association with BPA exposure and obesity.