Molecular mechanism for BPA-triggered hepatic steatosis

Exposure to Bisphenol A (BPA) has been linked to the increased incidence of nonalcoholic fatty liver disease (NAFLD): the hepatic manifestation of metabolic syndrome. In this study, male post-weaning C57BL/6 mice were exposed... [ view full abstract ]

Exposure to Bisphenol A (BPA) has been linked to the increased incidence of nonalcoholic fatty liver disease (NAFLD): the hepatic manifestation of metabolic syndrome. In this study, male post-weaning C57BL/6 mice were exposed to 50μg/kg/day BPA or corn oil for 90 days by. We found that insulin resistance, impaired hepatic lipid accumulation and increased serum triglycerides (TG) existed concomitantly in the BPA exposed mice. In addition, BPA exposure caused significant reduction in miR-192 expression in both mice liver tissues and human HepG2 cells, which were accompanied by significant up-regulation of SREBF1 (a key transcription factors that is capable of activate lipid synthesis) and subsequent expression of lipogenic genes. Bioinformatic and in vitro studies suggested that miR-192 acted to the 3’UTR of SREBF1 directly, resulting in profound dysregulations in hepatic lipid homeostasis. Inhibition of miR-192 led to higher TG levels and increased hepatic lipid accumulation by enhancing SREBF1 processing. In contrast, the opposite results were observed with overexpression of miR-192, which downregulated SREBF1 expression. Most importantly, we also showed that in vivo and in vitro overexpression of miR-192 effectively prevented BPA induced hepatic lipid accumulation, which was independently of insulin resistance. In conclusion, this study showed a novel mechanism that exposure to BPA may up-regulate SREBF1 through inhibition of miR-192 in the liver, thereby contributing to NAFLD.