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Institute of Reproductive and Developmental Biology, Imperial College London, London W12 ONN, United Kingdom
Address all correspondence and requests for reprints to: Roger White, Imperial College London, Institute of Reproductive and Developmental Biology, Hammersmith Campus, Du Cane Road, London W12 0NN, United Kingdom. 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 receptor interacting protein 140 (RIP140). Increased expression is mediated in part by the recruitment of peroxisome proliferator activated receptors 
and 
, together with estrogen-related receptor , 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 ß-adrenergic signaling is independent of RIP140, as shown by the action of the ß3-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 signaling pathways.
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