Journal
TOXICOLOGY IN VITRO
Volume 27, Issue 6, Pages 1634-1643Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2013.04.005
Keywords
Obesity; Epigenetics; Adipocyte differentiation; Endocrine disrupting chemicals; Bromodiphenylether; Tributyltin; In vitro
Categories
Funding
- European Community's Seventh Framework Programme [227391]
- Netherlands Organization for Scientific Research [NWO-VIDI 864.09.005]
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Recent studies suggest that endocrine disrupting chemicals (EDCs) may form a risk factor for obesity by altering energy metabolism through epigenetic gene regulation. The goal of this study is to investigate the effects of a range of EDCs with putative obesogenic properties on global DNA methylation and adipocyte differentiation in vitro. Murine N2A and human SK-N-AS neuroblastoma cells and murine preadipocyte fibroblasts (3T3-L1) were exposed to tributyltin (TBT), diethylstilbestrol (DES), bisphenol A (BPA), 2,3,7,8-tetrachlorodibenzo-[p]-dioxin (TCDD), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), hexachlorobenzene (HCB), hexabromocyclododecane (HBCD), 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47), perfluorinated octyl acid (PFOA) and perfluorinated octyl sulfonate (PFOS). A modest decrease in global DNA methylation was observed in N2A cells exposed to 10 mu M DES, BPA, TCDD, BDE-47, PCB-153 and 1 mu M HCB, but no changes were found in the human SK-N-AS cells. We reveal for the first time that BDE-47 increases adipocyte differentiation in a dose-dependent manner (2.5-25 mu M). Adipocyte differentiation was also enhanced by TBT (>= 10 nM) and BPA (>10 mu M) and inhibited by TCDD (>= 0.1 nM). The other chemicals showed either modest or no effects on adipocyte differentiation at the concentrations tested (PFOA, PFOS and HBCD at 10 mu M; PCB-153, 3.4 mu M and HCB, 1 mu M). This study demonstrates that selected EDCs can induce functional changes in murine adipocyte differentiation in vitro which are accompanied by decreased global DNA methylation. (C) 2013 Elsevier Ltd. All rights reserved.
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