Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism
| Autor: | Lu-Yang Jin, Kamran Ullah, Zhang-Hong Ke, Yi Cheng, Jun Ren, Tiantian Yu, Jian-Zhong Sheng, Jie-Xue Pan, Xin-Yan Dong, Tanzil Ur Rahman, Hai-Yan Xu, He-Feng Huang |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Blood Glucose DNA (Cytosine-5-)-Methyltransferase 1 Male medicine.medical_specialty endocrine system Methyltransferase 010501 environmental sciences Biology 01 natural sciences DNA methyltransferase Article Cell Line 03 medical and health sciences chemistry.chemical_compound Mice Phenols Internal medicine medicine Animals Obesity Benzhydryl Compounds RNA Small Interfering Gene Triglycerides 0105 earth and related environmental sciences Gene knockdown Multidisciplinary Cholesterol urogenital system Lipid metabolism DNA Methylation Lipid Metabolism Molecular biology 030104 developmental biology Endocrinology chemistry Adipose Tissue Liver DNA methylation Hepatocytes CpG Islands Female Reprogramming hormones hormone substitutes and hormone antagonists |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep31331 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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