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 language | English |
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Pages (from-to) | 24660-24669 |
Number of pages | 10 |
Journal | The Journal of Biological Chemistry |
Volume | 282 |
Issue number | 34 |
DOIs | |
Publication status | Published - 21 Jun 2007 |
Keywords
- element-binding protein
- amp response element
- adipose-tissue
- transcription factors
- mice lacking
- ppar-gamma
- differentiation
- coactivator
- adipogenesis
- activation