Literature DB >> 19962449

ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes.

Qin Hao1, Jacob B Hansen, Rasmus K Petersen, Philip Hallenborg, Claus Jørgensen, Saverio Cinti, Philip J Larsen, Knut R Steffensen, Haibo Wang, Sheila Collins, Jun Wang, Jan-Ake Gustafsson, Lise Madsen, Karsten Kristiansen.   

Abstract

Cold adaptation elicits a paradoxical simultaneous induction of fatty acid synthesis and beta-oxidation in brown adipose tissue. We show here that cold exposure coordinately induced liver X receptor alpha (LXRalpha), adipocyte determination and differentiation-dependent factor 1 (ADD1)/sterol regulatory element-binding protein-1c (SREBP1c) and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC1alpha) in brown and inguinal white adipose tissues, but not in epididymal white adipose tissue. Using in vitro models of white and brown adipocytes we demonstrate that beta-adrenergic stimulation induced expression of LXRalpha, ADD1/SREBP1c and PGC1alpha in cells with a brown-like adipose phenotype. We demonstrate that ADD1/SREBP1c is a powerful inducer of PGC1alpha expression via a conserved E box in the proximal promoter and that beta-adrenergic stimulation led to recruitment of ADD1/SREBP1c to this E box. The ability of ADD1/SREBP1c to activate the PGC1alpha promoter exhibited a striking cell type dependency, suggesting that additional cell type-restricted factors contribute to ADD1/SREBP1c-mediated activation. In conclusion, our data demonstrate a novel role of ADD1/SREBP1c as a regulator of PGC1alpha expression in brown adipose tissue. 2009 Elsevier B.V. All rights reserved.

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Year:  2009        PMID: 19962449     DOI: 10.1016/j.bbalip.2009.11.008

Source DB:  PubMed          Journal:  Biochim Biophys Acta        ISSN: 0006-3002


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