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dc.contributor.authorKamstra, JH-
dc.contributor.authorHruba, E-
dc.contributor.authorBlumberg, B-
dc.contributor.authorJanesick, A-
dc.contributor.authorMandrup, S-
dc.contributor.authorHamers, T-
dc.contributor.authorLegler, J-
dc.identifier.citationEnvironmental Science & Technology, 48, (7): pp. 4110 - 4119, (2014)en_US
dc.description.abstractRecent 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.extent4110 - 4119-
dc.publisherAmerican Chemical Societyen_US
dc.titleTranscriptional and epigenetic mechanisms underlying enhanced in vitro adipocyte differentiation by the brominated flame retardant BDE-47en_US
dc.relation.isPartOfEnvironmental Science & Technology-
Appears in Collections:Dept of Life Sciences Research Papers

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