title: Glucocorticoid Receptor Accelerates, but Is Dispensable for, Adipogenesis.
abstract: Dexamethasone (DEX), a synthetic ligand for glucocorticoid receptor (GR), is routinely used to stimulate adipogenesis in culture. GR-depleted preadipocytes show adipogenesis defects 1 week after induction of differentiation. However, it has remained unclear whether GR is required for adipogenesis in vivo By deleting GR in precursors of brown adipocytes, we found unexpectedly that GR is dispensable for brown adipose tissue development in mice. In culture, GR-deficient primary or immortalized white and brown preadipocytes showed severely delayed adipogenesis 1 week after induction of differentiation. However, when differentiation was extended to 3 weeks, GR-deficient preadipocytes showed levels of adipogenesis marker expression and lipid accumulation similar to those of the wild-type cells, indicating that DEX-bound GR accelerates, but is dispensable for, adipogenesis. Consistently, DEX accelerates, but is dispensable for, adipogenesis in culture. We show that DEX-bound GR accelerates adipogenesis by directly promoting the expression of adipogenic transcription factors CCAAT/enhancer-binding protein alpha (C/EBPα), C/EBPβ, C/EBPδ, KLF5, KLF9, and peroxisome proliferator-activated receptor γ (PPARγ) in the early phase of differentiation. Mechanistically, DEX-bound GR recruits histone H3K27 acetyltransferase CBP to promote activation of C/EBPβ-primed enhancers of adipogenic genes. These results clarify the role of GR in adipogenesis in vivo and demonstrate that DEX-mediated activation of GR accelerates, but is dispensable for, adipogenesis.
authors: Adipocyte Biology and Gene Regulation Section, LERB, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors: Young-Kwon
authors: YK
authors: Park
authors: Adipocyte Biology and Gene Regulation Section, LERB, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA kai.ge@nih.gov.
authors: Kai
authors: K
authors: Ge
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002478:Cells, Cultured; D003080:Cold Temperature; D003907:Dexamethasone / Q000494:pharmacology; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D003907:Dexamethasone; D006657:Histones; D008239:Lysine; D047495:PPAR gamma; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
keywords: GR; adipogenesis; dexamethasone; glucocorticoid receptor