Regulation of the third member of the uncoupling protein family, UCP3, by cold and thyroid hormone.
Uncoupling protein (UCP1) is a transmembrane proton transporter present in the mitochondria of brown adipose tissue (BAT), a specialized tissue which functions in temperature homeostasis and energy balance (Nicholls, D. G., and Locke, R. M. (1984) Physiol. Rev. 64, 2-40; Lowell, D. D., and Flier, J. S. (1997) Annu. Rev. Med.). UCP1 mediates the thermogenesis that is characteristic of BAT by uncoupling mitochondrial oxidation of substrates from ATP synthesis. Recently, two proteins related to UCP1 have been identified and designated UCP2 (Fleury, C., et al. (1997) Nature Genetics 15, 269-272) or UCP homolog (UCPH) (Gimeno, R. E., et al. (1997) Diabetes 46, 900-906) and UCP3 (Boss, O., et al. (1997) FEBS Lett. 408, 39-42; Vidal-Puig, A., et al. (1997) Biochem. Biophys. Res. Commun. 235, 79-82). We investigated the regulation in rats of UCP3, which is expressed primarily in skeletal muscle and BAT. Expression of rat UCP3 mRNA in BAT was upregulated by in vivo treatment with triiodothyronine (T3) and by exposure to cold, suggesting that UCP3 is active in thermogenesis and energy expenditure. In skeletal muscle, UCP3 mRNA was also upregulated by T3 but, surprisingly, not by cold exposure. A hypothesis is proposed to account for this differential regulation.
Larkin
S
S
Department of Pharmacology, Amylin Pharmaceuticals, Inc., San Diego, California 92121, USA.
Mull
E
E
Miao
W
W
Pittner
R
R
Albrandt
K
K
Moore
C
C
Young
A
A
Denaro
M
M
Beaumont
K
K
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism*; D003001:Cloning, Molecular; D003080:Cold Temperature; D004041:Dietary Fats / Q000008:administration & dosage; D006801:Humans; D007473:Ion Channels; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000008:administration & dosage / Q000494:pharmacology*; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D004041:Dietary Fats; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604392:UCP3 protein, human; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; D014284:Triiodothyronine