REGULATION OF THE 3RD MEMBER OF THE UNCOUPLING PROTEIN FAMILY, UCP3, BY COLD AND THYROID-HORMONE

Uncoupling protein (UCP1) is a transmembrane proton transporter presen t in the mitochondria of brown adipose tissue (BAT), a specialized tis sue which functions in temperature homeostasis and energy balance (Nic holls, 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 the rmogenesis that is characteristic of BAT by uncoupling mitochondrial o xidation of substrates from ATP synthesis. Recently, two proteins rela ted to UCP1 have been identified and designated UCP2 (Fleury, C., et a l. (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) FEES Lett. 408, 39-42; Vidal-Puig, A., et al. (1997) Biochem. B iophys. Res. Commun. 235, 79-82). We investigated the regulation in ra ts of UCP3, which is expressed primarily in skeletal muscle and BAT. E xpression of rat UCP3 mRNA in BAT was upregulated by in vivo treatment with triiodothyronine (T-3) and by exposure to cold, suggesting that UCP3 is active in thermogenesis and energy expenditure. In skeletal mu scle, UCP3 mRNA was also upregulated by T-3 but, surprisingly, not by cold exposure. A hypothesis is proposed to account for this differenti al regulation. (C) 1997 Academic Press.