Bézaire V, Hofmann W, Kramer J K, Kozak L P, Harper M E
Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Am J Physiol Endocrinol Metab. 2001 Nov;281(5):E975-82. doi: 10.1152/ajpendo.2001.281.5.E975.
Uncoupling protein-3 (UCP3) is a mitochondrial carrier protein of as yet undefined physiological function. To elucidate characteristics of its function, we studied the effects of fasting on resting metabolic rate, respiratory quotient, muscle Ucp3 expression, and mitochondrial proton leak in wild-type and Ucp3(-/-) mice. Also analyzed were the fatty acid compositions of skeletal muscle mitochondria in fed and fasted Ucp3(-/-) and wild-type mice. In wild-type mice, fasting caused significant increases in Ucp3 (4-fold) and Ucp2 (2-fold) mRNA but did not significantly affect mitochondrial proton leak. State 4 oxygen consumption was not affected by fasting in either of the two groups. However, protonmotive force was consistently higher in mitochondria of Ucp3(-/-) animals (P = 0.03), and fasting further augmented protonmotive force in Ucp3(-/-) mice; there was no effect in wild-type mitochondria. Resting metabolic rates decreased with fasting in both groups. Ucp3(-/-) mice had higher respiratory quotients than wild-type mice in fed resting states, indicating impaired fatty acid oxidation. Altogether, results show that the fasting-induced increases in Ucp2 and Ucp3 do not correlate with increased mitochondrial proton leak but support a role for UCP3 in fatty acid metabolism.
解偶联蛋白3（UCP3）是一种线粒体载体蛋白，其生理功能尚未明确。为了阐明其功能特性，我们研究了禁食对野生型和Ucp3基因敲除小鼠静息代谢率、呼吸商、肌肉Ucp3表达以及线粒体质子泄漏的影响。同时，我们还分析了喂食和禁食状态下Ucp3基因敲除小鼠及野生型小鼠骨骼肌线粒体的脂肪酸组成。在野生型小鼠中，禁食导致Ucp3（4倍）和Ucp2（2倍）mRNA显著增加，但对线粒体质子泄漏没有显著影响。两组小鼠的状态4氧消耗量均不受禁食影响。然而，Ucp3基因敲除动物线粒体中的质子动力势始终较高（P = 0.03），禁食进一步增强了Ucp3基因敲除小鼠的质子动力势；野生型线粒体则无此效应。两组小鼠的静息代谢率均随禁食而降低。在喂食后的静息状态下，Ucp3基因敲除小鼠的呼吸商高于野生型小鼠，表明脂肪酸氧化受损。总之，结果表明禁食诱导的Ucp2和Ucp3增加与线粒体质子泄漏增加无关，但支持UCP3在脂肪酸代谢中的作用。
