Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold
Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold
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DOI：
10.1096/fj.00-0536fje
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发表时间：
2001-07-01
期刊：
影响因子：
4.8
通讯作者：
Nedergaard, J
中科院分区：
文献类型：
--
作者：
Golozoubova, V;Hohtola, E;Nedergaard, J
适应性非颤抖性产热可能对能量平衡有深远的影响，因此是对抗肥胖发展的潜在机制。适应性非颤抖性产热的分子基础仍然是一个挑战，引发了对蛋白质（UCP 2，UCP 3等）鉴定的强烈兴趣。与原始解偶联蛋白-1（UCP 1）具有高度序列相似性，UCP 1仅位于棕色脂肪组织中。使用UCP 1消融小鼠，我们研究了是否可以通过适应寒冷来招募任何适应性非颤抖性产热。值得注意的是，通过连续的适应，UCP 1消融的小鼠可以在4摄氏度下生存数周，在此期间，它们必须不断产生四倍于其静息水平的热量。然而，尽管适应性非颤抖性产热有这些极端的要求，但没有任何适应性非颤抖性产热过程取代颤抖。因此，虽然存在的，例如，肌肉机制的适应性nonshriving产热已经反复暗示，我们没有发现任何迹象表明，这种产热。即使在对额外热量产生的长期和增强的需求中，任何内源性激素或神经递质都不能在肌肉或任何其他器官中招募任何不依赖UCP 1的适应性非颤抖性产热过程，因此除了UCP 1之外，没有任何蛋白质-甚至UCP 2或UCP 3-有能力在寒冷中介导适应性非颤抖性产热。
Adaptive nonshivering thermogenesis may have profound effects on energy balance and is therefore therefore is a potential mechanism for counteracting the development of obesity. The molecular basis for adaptive nonshivering thermogenesis has remained a challenge that sparked acute interest with the identification of proteins (UCP2, UCP3, etc.) with high-sequence similarity to the original uncoupling protein-1 (UCP1), which is localized only in brown adipose tissue. Using UCP1-ablated mice, we examined whether any adaptive nonshivering thermogenesis could be recruited by acclimation to cold. Remarkably, by successive acclimation, the UCP1-ablated mice could be made to subsist for several weeks at 4 degreesC during which they had to constantly produce heat at four times their resting levels. Despite these extreme requirements for adaptive nonshivering thermogenesis, however, no substitution of shivering by any adaptive nonshivering thermogenic process occurred. Thus, although the existence of, for example, muscular mechanisms for adaptive nonshivering thermogenesis has recurrently been implied, we did not find any indication of such thermogenesis. Not even during prolonged and enhanced demand for extra heat production was any endogenous hormone or neurotransmitter able to recruit any UCP1-independent adaptive nonshivering thermogenic process in muscle or in any other organ, and no proteins other than UCP1-not even UCP2 or UCP3-therefore have the ability to mediate adaptive nonshivering thermogenesis in the cold.