title: Bisphenol A increases aP2 expression in 3T3L1 by enhancing the transcriptional activity of nuclear receptors at the promoter.
abstract: Environmental pollutants, such as bisphenol A (BPA), have the potential to affect the differentiation processes and the biology of the adipose tissue. The 3T3-L1 model is one of the murine cell models used extensively for the investigation of the molecular events that govern the differentiation of adipocytes from a committed preadipocyte to a mature, lipid laden adipocyte. Most of the studies investigating the effects of BPA on preadipocyte differentiation have investigated the effects of this chemical in the presence of an optimal differentiation cocktail containing high concentrations of the synthetic glucocorticoid dexamethasone, conditions that result in 90% to 100% of differentiated adipocytes. Our studies employed the 3T3-L1 cell model in the absence of exogenous glucocorticoids. We show that BPA is able to increase the differentiation of the 3T3-L1 cells under these conditions. Furthermore, the effect of BPA was observed in the absence of the synthetic glucocorticoid (dexamethasone), a hormone known to be required for the differentiation of the 3T3-L1 cells. In addition, BPA upregulated the mRNA expression and protein levels of the terminal marker of adipogenesis the fatty acid binding protein (aP2) in these cells. Interestingly, the known modulators of adipogenesis such as the peroxisome proliferator-activated receptor (PPAR) γ or CCAAT enhancer binding protein (C/EBP) α were not elevated at the mRNA or protein level in response to BPA. Furthermore, BPA upregulated the expression levels of the marker of adipogenesis aP2, through an effect on the transcriptional activity of C/EBPδ and the glucocorticoid receptor (GR) at its promoter.
authors: Health Canada; Environmental Health Science and Research Bureau; Ottawa, ON Canada.
authors: Ella
authors: E
authors: Atlas
authors: Health Canada; Environmental Health Science and Research Bureau; Ottawa, ON Canada.
authors: Louise
authors: L
authors: Pope
authors: Health Canada; Environmental Health Science and Research Bureau; Ottawa, ON Canada.
authors: Mike G
authors: MG
authors: Wade
authors: Health Canada; Environmental Health Science and Research Bureau; Ottawa, ON Canada.
authors: Alice
authors: A
authors: Kawata
authors: Health Canada; Environmental Health Science and Research Bureau; Ottawa, ON Canada.
authors: Adele
authors: A
authors: Boudreau
authors: Health Canada; Environmental Health Science and Research Bureau; Ottawa, ON Canada.
authors: Jonathan G
authors: JG
authors: Boucher
keywords: C/EBPδ; GR; aP2; adipocyte differentiation; adipogenesis; bisphenol A; differentiation; glucocorticoid receptor; transcription