Dataset Information

Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism.

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??g 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.

SUBMITTER: Ke ZH

PROVIDER: S-EPMC4977563 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism.

Ke Zhang-Hong ZH Pan Jie-Xue JX Jin Lu-Yang LY Xu Hai-Yan HY Yu Tian-Tian TT Ullah Kamran K Rahman Tanzil Ur TU Ren Jun J Cheng Yi Y Dong Xin-Yan XY Sheng Jian-Zhong JZ Huang He-Feng HF

Scientific reports 20160809

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 ...[more]

PMID: 27502578

Similar Datasets

Project description:Preeclampsia leads to adverse outcomes for pregnant women. Bisphenol A (BPA) is an environmental endocrine disruptor and has been shown to be positively associated with increased risk of preeclampsia in human studies. We investigated whether BPA exposure causes preeclampsia-like features in pregnant mice and the associated underlying mechanisms. Experiments were performed in animal models and cell cultures. In pregnant mice, BPA-exposed mice exhibited preeclampsia-like features including hypertension, disruption of the circulation, and the placental angiogenesis biomarkers fms-related tyrosine kinase 1 and placenta growth factor, and glomerular atrophy; urinary protein was not affected. These preeclampsia-like features correlated with increased retention of smooth muscle cells and reduced vessel areas at the junctional zone of the placenta. In addition, there were disrupted expression of invasion-related genes including increased tissue inhibitors of metalloproteinases, decreased metalloproteinases, and Wnt family member WNT2/β-catenin, which correlated with increased DNA methylation in its promoter region and upregulation of DNA methyltransferase (Dnmt)1. BPA exposure impeded the interaction between the human cytotrophoblast cell line, HTR-8/SVneo, and endothelium cells. BPA exposure down-regulated WNT2 expression, and elevated the DNA methylation of WNT2; these results were consistent with in vivo observations. Inhibition of DNMT in HTR-8/SVneo cells resulted in reduced DNA methylation and increased expression of WNT2. Taken together, these data demonstrate that BPA exposure alters trophoblast cell invasion and causes abnormal placental vessel remodeling, both of which lead to the development of preeclampsia-like features in pregnant mice. Our results suggest that this phenomenon involves the epigenetic reprogramming and down-regulation of WNT2 mediated by DNMT1.-Ye, Y., Tang, Y., Xiong, Y., Feng, L., Li, X. Bisphenol A exposure alters placentation and causes preeclampsia-like features in pregnant mice involved in reprogramming of DNA methylation of WNT2.

Dataset Information

Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism.

Publications

Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets