Details

Autor(en) / Beteiligte

• Lin, Yi
• Ding, Dongxiao
• Huang, Qiansheng
• Liu, Qiong
• Lu, Haoyang
• Lu, Yanyang
• Chi, Yulang
• Sun, Xia
• Ye, Guozhu
• Zhu, Huimin
• Wei, Jie
• Dong, Sijun

Titel

Downregulation of miR-192 causes hepatic steatosis and lipid accumulation by inducing SREBF1: Novel mechanism for bisphenol A-triggered non-alcoholic fatty liver disease

Ist Teil von

• Biochimica et biophysica acta. Molecular and cell biology of lipids, 2017-09, Vol.1862 (9), p.869-882

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Exposure to Bisphenol A (BPA) has been associated with the development of nonalcoholic 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 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 mouse 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 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 a novel mechanism in which NAFLD associated with BPA exposure arose from alterations in the miR-192-SREBF1 axis. •BPA downregulates miR-192 via inhibition of miR-192 maturation.•SREBF1 is a direct target of miR-192.•BPA induced-miR-192 deficiency serves to raise SREBF1, thus promoting the development of NAFLD.