About: Transcriptional and Epigenetic Mechanisms Underlying Enhanced in Vitro Adipocyte Differentiation by the Brominated Flame Retardant BDE-47     Goto   Sponge   NotDistinct   Permalink

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  • 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 (PPAR gamma) in COS7 cells, transiently transfected with a GAL4 reporter construct. Increased gene expression was observed for Ppar gamma 2, 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 Ppar gamma 2 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 Ppar gamma 2 gene induction and promoter demethylation accompanied by activation of PPAR gamma, and possible disruption of glucose homeostasis and IGF1 signaling.
  • 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 (PPAR gamma) in COS7 cells, transiently transfected with a GAL4 reporter construct. Increased gene expression was observed for Ppar gamma 2, 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 Ppar gamma 2 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 Ppar gamma 2 gene induction and promoter demethylation accompanied by activation of PPAR gamma, and possible disruption of glucose homeostasis and IGF1 signaling. (en)
Title
  • Transcriptional and Epigenetic Mechanisms Underlying Enhanced in Vitro Adipocyte Differentiation by the Brominated Flame Retardant BDE-47
  • Transcriptional and Epigenetic Mechanisms Underlying Enhanced in Vitro Adipocyte Differentiation by the Brominated Flame Retardant BDE-47 (en)
skos:prefLabel
  • Transcriptional and Epigenetic Mechanisms Underlying Enhanced in Vitro Adipocyte Differentiation by the Brominated Flame Retardant BDE-47
  • Transcriptional and Epigenetic Mechanisms Underlying Enhanced in Vitro Adipocyte Differentiation by the Brominated Flame Retardant BDE-47 (en)
skos:notation
  • RIV/00027162:_____/14:#0001184!RIV15-MZE-00027162
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • N
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  • 7
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http://linked.open...dnocenehoVysledku
  • 50981
http://linked.open...ai/riv/idVysledku
  • RIV/00027162:_____/14:#0001184
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • DNA METHYLATION; 3T3-L1 ADIPOCYTES; PPAR-GAMMA; STEM-CELLS; OBESITY EPIDEMIC; ADIPOGENESIS; EXPOSURE; RECEPTOR; EXPRESSION; REGULATOR (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [F8217BA89EAA]
http://linked.open...i/riv/nazevZdroje
  • Environmental Science & Technology
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 48
http://linked.open...iv/tvurceVysledku
  • Hamers, T.
  • Kamstra, J. H.
  • Hrubá, Eva
  • Legler, J.
  • Blumberg, B.
  • Janesick, A.
  • Mandrup, S.
http://linked.open...ain/vavai/riv/wos
  • 000333776100062
issn
  • 0013-936X
number of pages
http://bibframe.org/vocab/doi
  • 10.1021/es405524b
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