Bisphenol A could risk factor for non-alcoholic fatty liver disease. - GreenMedInfo Summary
Downregulation of miR-192 Causes Hepatic Steatosis and Lipid Accumulation by Inducing SREBF1: Novel Mechanism for Bisphenol A-triggered Non-alcoholic Fatty Liver Disease.
Biochim Biophys Acta. 2017 May 5. Epub 2017 May 5. PMID: 28483554
Exposure to Bisphenol A (BPA) has been associated with the development of non-alcoholic fatty liver disease (NAFLD) but the underlying mechanism remains unclear. Given that microRNA (miRNA) is recognized as a key regulator of lipid metabolism and a potential mediator of environmental cues, this study was designed to explore whether exposure to BPA-triggered abnormal steatosis and whether lipid accumulation in the liver could be modulated by miR-192. We showed that male post-weaning C57BL/6 mice exposed to 50μg/kg/day of BPA by oral gavage for 90days displayed a NAFLD-like phenotype. In addition, we found in mice liver and human HepG2 cells that BPA-induced hepatic steatosis and lipid accumulation were associated with decreased expression of miR-192, upregulation of SREBF1 and a series of genes involved in de novo lipogenesis. Downregulation of miR-192 in BPA-exposed hepatocytes could be due to defective pre-miR-192 processing of by DROSHA. Using HepG2 cells, we further confirmed that miR-192 directly acted on the 3'UTR of SREBF1, contributing to dysregulation of lipid homeostasis in hepatocytes.MiR-192 mimic and lentivirus-mediated overexpression of miR-192 improved BPA-induced hepatic steatosis by suppressing SREBF1. Lastly, we noted that lipid accumulation was not a strict requirement for developing insulin resistance in mice after BPA treatment. In conclusion, this study demonstrated anovel mechanism in which NAFLD associated with BPA exposure arose from alterations in the miR-192-SREBF1 axis.