Receptor interacting protein 140 regulates expression of uncoupling protein 1 in adipocytes through specific peroxisome proliferator activated receptor isoforms and estrogen-related receptor alpha.
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 alpha and gamma, together with estrogen-related receptor 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 signaling 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 signaling pathways.
Debevec
Darja
D
Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0NN, United Kingdom.
Christian
Mark
M
Morganstein
Daniel
D
Seth
Asha
A
Herzog
Birger
B
Parker
Malcolm
M
White
Roger
R
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D007473:Ion Channels / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000078723:Nuclear Receptor Interacting Protein 1; D047493:PPAR alpha / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D000071256:Uncoupling Protein 1; D000097983:ERRalpha Estrogen-Related Receptor
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D007473:Ion Channels; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D047493:PPAR alpha; D047495:PPAR gamma; D012333:RNA, Messenger; D022702:Receptors, Adrenergic, beta-3; D011960:Receptors, Estrogen; D000071256:Uncoupling Protein 1; D000097983:ERRalpha Estrogen-Related Receptor; C000604372:Ucp1 protein, mouse