C/EBPß Reprograms White 3T3-L1 Preadipocytes to a Brown Adipocyte Pattern of Gene Expression

Georgios Karamanlidis, Angeliki Karamitri, Kevin Docherty, David G. Hazlerigg, Michael A. Lomax

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Abstract

cAMP-dependent protein kinase induction of PPAR (gamma) coactivator-1alpha (PGC-1alpha) and uncoupling protein 1 (UCP1) expression is an essential step in the commitment of preadipocytes to the brown adipose tissue (BAT) lineage. We studied the molecular mechanisms responsible for differential expression of PGC-1alpha in HIB1B (BAT) and 3T3-L1 white adipose tissue (WAT) precursor cell lines. In HIB1B cells PGC-1alpha and UCP1 expression is cAMP-inducible, but in 3T3-L1 cells, expression is reduced and is cAMP-insensitive. A proximal 264-bp PGC-1alpha reporter construct was cAMP-inducible only in HIB1B cells and was suppressed by site-directed mutagenesis of the proximal cAMP response element (CRE). In electrophoretic mobility shift assays, the transcription factors CREB and C/EBPß, but not C/EBPa and C/EBPd, bound to the CRE on the PGC-1alpha promoter region in HIB1B and 3T3-L1 cells. Chromatin immunoprecipitation studies demonstrated that C/EBPß and CREB bound to the CRE region in HIB1B and 3T3-L1 cell lysates. C/EBPß expression was induced by cAMP only in HIB1B cells, and overexpression of C/EBPß rescued cAMP-inducible PGC-1alpha and UCP1 expression in 3T3-L1 cells. These data demonstrate that differentiation of preadipocytes toward the BAT rather than the WAT phenotype is controlled in part by the action of C/EBPß on the CRE in PGC-1alpha proximal promoter.

Original languageEnglish
Pages (from-to)24660-24669
Number of pages10
JournalThe Journal of Biological Chemistry
Volume282
Issue number34
DOIs
Publication statusPublished - 21 Jun 2007

Keywords

  • element-binding protein
  • amp response element
  • adipose-tissue
  • transcription factors
  • mice lacking
  • ppar-gamma
  • differentiation
  • coactivator
  • adipogenesis
  • activation

Cite this

Karamanlidis, G., Karamitri, A., Docherty, K., Hazlerigg, D. G., & Lomax, M. A. (2007). C/EBPß Reprograms White 3T3-L1 Preadipocytes to a Brown Adipocyte Pattern of Gene Expression. The Journal of Biological Chemistry, 282(34), 24660-24669. https://doi.org/10.1074/jbc.M703101200