Energy metabolism in uncoupling protein 3 gene knockout mice
Energy metabolism in uncoupling protein 3 gene knockout mice
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DOI：
10.1074/jbc.m910179199
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发表时间：
2000-05-26
影响因子：
4.8
通讯作者：
Lowell, BB
中科院分区：
文献类型：
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作者：
Vidal-Puig, AJ;Grujic, D;Lowell, BB
解偶联蛋白3 （UCP3）是线粒体阴离子载体超家族的成员。基于UCP3与UCP1的高度同源性，以及UCP3在骨骼肌和棕色脂肪组织中的限制性组织分布，UCP3被认为在调节能量消耗、体重和体温调节中发挥重要作用。UCP3的其他作用包括调节脂肪酸代谢，对急性运动和饥饿的适应性反应，以及防止活性氧（ROS）的形成。为了解决这些问题，我们培育了缺乏UCP3的小鼠（UCP3敲除（KO）小鼠）。在这里，我们提供的证据表明，缺乏UCP3的骨骼肌线粒体更偶联（即增加状态3/状态4比率），表明UCPB具有解偶联活性。此外，缺乏UCP3的线粒体中ROS的产生增加。本研究表明，UCP3具有解偶联活性，其缺失可能导致ROS的产生增加。尽管对线粒体功能有这些影响，但UCP3似乎并不是体重调节、运动耐量、脂肪酸氧化或冷致产热所必需的。UCP3 KO小鼠中这些表型的缺失不能归因于其他UCP mrna的上调。然而，不能排除其他补偿机制。UCP3 KO小鼠线粒体偶联增加对代谢的影响以及尚未确定的代偿机制的可能作用仍有待确定。
Uncoupling protein 3 (UCP3) is a member of the mitochondrial anion carrier superfamily. Based upon its high homology with UCP1 and its restricted tissue distribution to skeletal muscle and brown adipose tissue, UCP3 has been suggested to play important roles in regulating energy expenditure, body weight, and thermoregulation. Other postulated roles for UCP3 include regulation of fatty acid metabolism, adaptive responses to acute exercise and starvation, and prevention of reactive oxygen species (ROS) formation. To address these questions, we have generated mice lacking UCP3 (UCP3 knockout (KO) mice). Here, we provide evidence that skeletal muscle mitochondria lacking UCP3 are more coupled (i.e. increased state 3/state 4 ratio), indicating that UCPB has uncoupling activity. In addition, production of ROS is increased in mitochondria lacking UCP3. This study demonstrates that UCP3 has uncoupling activity and that its absence may lead to increased production of ROS. Despite these effects on mitochondrial function, UCP3 does not seem to be required for body weight regulation, exercise tolerance, fatty acid oxidation, or cold-induced thermogenesis. The absence of such phenotypes in UCP3 KO mice could not be attributed to up-regulation of other UCP mRNAs. However, alternative compensatory mechanisms cannot be excluded. The consequence of increased mitochondrial coupling in UCP3 KO mice on metabolism and the possible role of yet unidentified compensatory mechanisms, remains to be determined.