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首页> 外文期刊>Environmental Science & Technology >Transcriptional and Epigenetic Mechanisms Underlying Enhanced in Vitro Adipocyte Differentiation by the Brominated Flame Retardant BDE-47
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Transcriptional and Epigenetic Mechanisms Underlying Enhanced in Vitro Adipocyte Differentiation by the Brominated Flame Retardant BDE-47

机译：溴化阻燃剂BDE-47增强体外脂肪细胞分化的转录和表观遗传机制。

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摘要

Recent studies suggest that exposure to endocrine-disrupting compounds (EDCs) may play a role in the development of obesity. EDCs such as the flame retardant 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47) have been shown to enhance adipocyte differentiation in the murine 3T3-L1 model. The mechanisms by which EDCs direct preadipocytes to form adipocytes are poorly understood. Here, we examined transcriptional and epigenetic mechanisms underlying the induction of in vitro adipocyte differentiation by BDE-47. Quantitative high content microscopy revealed concentration-dependent enhanced adipocyte differentiation following exposure to BDE-47 or the antidiabetic drug troglitazone (TROG). BDE-47 modestly activated the key adipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) in COS7 cells, transiently transfected with a GAL4 reporter construct. Increased gene expression was observed for 'Pparγ2, leptin (Lep), and glucose-6-phophatase catalytic subunit (G6pc) in differentiated 3T3-L1 cells after BDE-47 exposure compared to TROG. Methylation-sensitive high resolution melting (MS-HRM) revealed significant demethylation of three CpG sites in the Pparγ2 promoter after exposure to both BDE-47 and TROG in differentiated 3T3-L1 cells. This study shows the potential of BDE-47 to induce adipocyte differentiation through various mechanisms that include Pparγ2 gene induction and promoter demethylation accompanied by activation of PPARγ, and possible disruption of glucose homeostasis and IGF1 signaling.
机译：最近的研究表明，暴露于破坏内分泌的化合物（EDC）可能在肥胖症的发展中起作用。 EDC，如阻燃剂2,2'，4,4'-四溴联苯醚（BDE-47）已显示在鼠3T3-L1模型中可增强脂肪细胞分化。 EDC指导前脂肪细胞形成脂肪细胞的机制了解甚少。在这里，我们检查了由BDE-47诱导体外脂肪细胞分化的转录和表观遗传机制。定量高含量显微镜显示暴露于BDE-47或抗糖尿病药物曲格列酮（TROG）后，浓度依赖性脂肪细胞分化增强。 BDE-47在COS7细胞中适度激活了关键的成脂转录因子过氧化物酶体增殖物激活的受体γ（PPARγ），该细胞被GAL4报告基因构建体瞬时转染。与TROG相比，在BDE-47暴露后，分化的3T3-L1细胞中的'Pparγ2，瘦素（Lep）和葡萄糖-6-磷酸酶催化亚基（G6pc）的基因表达增加。甲基化敏感的高分辨率熔解（MS-HRM）显示，在分化的3T3-L1细胞中，暴露于BDE-47和TROG后，Pparγ2启动子中的三个CpG位点显着脱甲基。这项研究表明，BDE-47具有通过多种机制诱导脂肪细胞分化的潜力，包括Pparγ2基因诱导和启动子去甲基化以及PPARγ活化，以及葡萄糖稳态和IGF1信号转导的破坏。

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  • 来源
    《Environmental Science & Technology》 |2014年第7期|4110-4119|共10页
  • 作者

    Jorke H. Kamstra; Eva Hruba; Bruce Blumberg; Amanda Janesick; Susanne Mandrup; Timo Hamers; Juliette Legler;

  • 作者单位

    Institute for Environmental Studies, VU University Amsterdam, Amsterdam, 1081HV, The Netherlands;

    Department of Chemistry and Toxicology, Veterinary Research Institute, Brno, 621 00, Czech Republic;

    Department of Developmental and Cell Biology and Department of Pharmaceutical Sciences, University of California-Irvine, Irvine, California, 92697, United States;

    Department of Developmental and Cell Biology and Department of Pharmaceutical Sciences, University of California-Irvine, Irvine, California, 92697, United States;

    Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark, DK-5230;

    Institute for Environmental Studies, VU University Amsterdam, Amsterdam, 1081HV, The Netherlands;

    Institute for Environmental Studies, VU University Amsterdam, Amsterdam, 1081HV, The Netherlands;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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