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DC Field | Value | Language |
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dc.contributor.author | Kamstra, JH | - |
dc.contributor.author | Hruba, E | - |
dc.contributor.author | Blumberg, B | - |
dc.contributor.author | Janesick, A | - |
dc.contributor.author | Mandrup, S | - |
dc.contributor.author | Hamers, T | - |
dc.contributor.author | Legler, J | - |
dc.date.accessioned | 2016-04-07T08:47:30Z | - |
dc.date.available | 2014-04 | - |
dc.date.available | 2016-04-07T08:47:30Z | - |
dc.date.issued | 2014 | - |
dc.identifier.citation | Environmental Science & Technology, 48, (7): pp. 4110 - 4119, (2014) | en_US |
dc.identifier.issn | 0013-936X | - |
dc.identifier.issn | 1520-5851 | - |
dc.identifier.uri | http://pubs.acs.org/doi/abs/10.1021/es405524b | - |
dc.identifier.uri | http://bura.brunel.ac.uk/handle/2438/12457 | - |
dc.description.abstract | 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. | en_US |
dc.format.extent | 4110 - 4119 | - |
dc.language.iso | en | en_US |
dc.publisher | American Chemical Society | en_US |
dc.title | Transcriptional and epigenetic mechanisms underlying enhanced in vitro adipocyte differentiation by the brominated flame retardant BDE-47 | en_US |
dc.type | Article | en_US |
dc.identifier.doi | http://dx.doi.org/10.1021/es405524b | - |
dc.relation.isPartOf | Environmental Science & Technology | - |
pubs.issue | 7 | - |
pubs.publication-status | Published | - |
pubs.volume | 48 | - |
Appears in Collections: | Dept of Life Sciences Research Papers |
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Fulltext.pdf | 4.09 MB | Adobe PDF | View/Open |
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