Abstract
Accumulating evidence suggests a role of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism is still unclear. Using a mouse BPA exposure model, we investigated the effects of long-term BPA exposure on lipid metabolism and the underlying mechanisms. The male mice exposed to BPA (0.5 μg BPA /kg/day, a human relevant dose) for 10 months exhibited significant hepatic accumulation of triglycerides and cholesterol. The liver cells from the BPA-exposed mice showed significantly increased expression levels of the genes related to lipid synthesis. These liver cells showed decreased DNA methylation levels of Srebf1 and Srebf2, and increased expression levels of Srebf1 and Srebf2 that may upregulate the genes related to lipid synthesis. The expression levels of DNA methyltransferases were decreased in BPA-exposed mouse liver. Hepa1-6 cell line treated with BPA showed decreased expression levels of DNA methyltransferases and increased expression levels of genes involved in lipid synthesis. DNA methyltransferase knockdown in Hepa1-6 led to hypo-methylation and increased expression levels of genes involved in lipid synthesis. Our results suggest that long-term BPA exposure could induce hepatic lipid accumulation, which may be due to the epigenetic reprogramming of the genes involved in lipid metabolism, such as the alterations of DNA methylation patterns.
Highlights
Mounting epidemiologic studies have revealed the association of bisphenol A (BPA) exposure and metabolic disorders, such as cardiovascular diseases, diabetes and liver damage[4]
To explore the mechanistic link between changes in the expression and changes in the DNA methylation, we examined whether BPA treatment in Hepa[1,2,3,4,5,6] mouse hepatocyte cell line might directly alter the expression of DNA methyltransferases, and, whether knockdown of DNMTs could affect the DNA methylation and expression of genes involved in lipid synthesis
We explored the effect of BPA treatment on the expression of genes involved in lipid synthesis in Hepa[1,2,3,4,5,6], and, the effect of Srebf[1] and Srebf[2] knockdown on the transcription of genes involved in lipid synthesis
Summary
Mounting epidemiologic studies have revealed the association of BPA exposure and metabolic disorders, such as cardiovascular diseases, diabetes and liver damage[4]. One group administered adult male mice with doses (5, 50, 500, and 5,000 μg/kg/day) of BPA for both 4 weeks[4] and 8 months[9], and observed disruption of hepatic lipid metabolism in BPA-exposed mice with both protocols. Molecular mechanisms that underlie DNA methylation-related hepatic lipid accumulation are not thoroughly illustrated, and, the role of DNA methylation in BPA-induced hepatic steatosis remains to be examined[17]. We compared the metabolic indexes of 8-weeks and 10-months old male mice between control and BPA exposure groups, and, analyzed the gene expression levels of the key players in hepatic lipid metabolism to illustrate the mechanisms underlying the dyslipidemia and hepatic lipid accumulation after long-term BPA exposure. We explored the effect of BPA treatment on the expression of genes involved in lipid synthesis in Hepa[1,2,3,4,5,6], and, the effect of Srebf[1] and Srebf[2] knockdown on the transcription of genes involved in lipid synthesis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
