Bisphenol A disrupts apolipoprotein E expression through estrogen-related receptor gamma and DNA methlylation in the liver of male rare minnow Gobiocypris rarus

Abstract

An increasing number of studies show that bisphenol A (BPA) can cause lipid metabolism disorder. However, few studies focused on the effect of BPA on lipid transport. Apolipoprotein E (ApoE) plays important roles in triglyceride (TG) transportation. Our previous study found that ApoE was a sensitive gene in response to BPA exposure in male rare minnow. To investigate the effect and mechanism of BPA on hepatic ApoE, adult male rare minnow Gobiocypris rarus were exposed to environmentally relevant concentrations of BPA (15 μg/L) for 1, 3 and 5 weeks. Results showed that BPA inhibited ApoE expression at week 1 and 5, while induced its expression at week 3. A positive estrogen-related receptor gamma (Esrrg) response element was identified in the promoter region of ApoE. The change of the Esrrg recruitment was consistent with ApoE mRNA expression. Moreover, the methylation status of the CpG sites near and on the Esrrg binding sites changed opposite to the ApoE mRNA level, which may be the main cause for the change in Esrrg recruitment. The expression of ApoE protein was significantly enhanced following long-term BPA exposure. Consistently, the TG accumulation was significantly increased in the plasma. The present study demonstrates that BPA could affect rare minnow ApoE expression, which is probably one of the ways for BPA disturbing fish lipid metabolism.