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This version published online on April 24, 2007
Molecular Endocrinology, doi:10.1210/me.2007-0103
A more recent version of this article appeared on July 1, 2007
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Submitted on February 23, 2007
Accepted on April 16, 2007

RIP140 regulates expression of Uncoupling Protein 1 in adipocytes through specific PPAR isoforms and ERR{alpha}

Darja Debevec, Mark Christian, Daniel Morganstein, Asha Seth, Malcolm Parker, and Roger White*

Institute of Reproductive and Developmental Biology, Imperial College London, Du Cane Rd, London W12 ONN UK

* To whom correspondence should be addressed. E-mail: roger.white{at}imperial.ac.uk.

Expression of uncoupling protein 1 (Ucp1) mRNA is elevated in differentiated adipocytes derived from brown or white adipose tissue devoid of the nuclear receptor corepressor RIP140. Increased expression is mediated in part by the recruitment of PPAR{alpha} and PPAR{gamma}, together with ERR{alpha} which functions through a novel binding site on the Ucp1 enhancer. This demonstrates that regulation of Ucp1 expression in the absence of RIP140 involves derepression of at least three different nuclear receptors. The ability to increase expression of Ucp1 by {beta}-adrenergic signalling is independent of RIP140, as shown by the action of the {beta}3-adrenergic agonist CL 316,243 to stimulate expression in both brown and white adipocytes in the presence and absence of the corepressor. Therefore the expression of this metabolic uncoupling protein in adipose cells is regulated by inhibition as well as activation of distinct signalling pathways.

NURSA Molecule Pages Link:

Nuclear Receptors:   PPARα  |  PPARδ  |  PPARγ  |  ERRα
Coregulators:   RIP140  |  PGC-1  |  PGC-1β
Ligands:   GW 7647  |  GW6471  |  XCT790  |  Rosiglitazone



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