Uncoupling proteins: functional characteristics and role in the pathogenesis of obesity and Type II diabetes
Uncoupling proteins: functional characteristics and role in the pathogenesis of obesity and Type II diabetes
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DOI：
10.1007/s001250100596
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发表时间：
2001-08-01
期刊：
影响因子：
8.2
通讯作者：
Pedersen, O
中科院分区：
文献类型：
--
作者：
Dalgaard, LT;Pedersen, O
解偶联蛋白是线粒体载体蛋白，其能够消散线粒体内膜的质子梯度。这种解偶联过程减少了通过燃料氧化产生的ATP的量。解偶联蛋白（UCPs）是人类肥胖或II型（非胰岛素依赖型）糖尿病的候选基因的假设是基于线粒体膜的化学解偶联减少身体肥胖的发现，并且较低的代谢率预测体重增加。可以直接假设UCP1、UCP2和UCP3基因的常见多态性通过线粒体中更有效的能量偶联降低代谢率。此外，过表达不同UCP同源物的基因工程小鼠是瘦的，并且对饮食诱导的肥胖有抵抗力。已经研究了三种解偶联蛋白同源基因UCP1、UCP2和UCP3的多态性和突变及其对II型糖尿病、肥胖和体重增加或BMI的影响。主要结论是UCP1、UCP2或UCP3基因的变异与体重增加的重大变化无关。UCP基因对多基因肥胖和II型糖尿病的贡献进行了评估和讨论。
Uncoupling proteins are mitochondrial carrier proteins which are able to dissipate the proton gradient of the inner mitochondrial membrane. This uncoupling process reduces the amount of ATP generated through an oxidation of fuels. The hypothesis that uncoupling proteins (UCPs) are candidate genes for human obesity or Type II (non-insulin-dependent) diabetes mellitus is based on the finding that a chemical uncoupling of the mitochondrial membrane reduces body adiposity, and that lower metabolic rates predict weight gain. It is straightforward to hypothesize that common polymorphisms of UCP1, UCP2 and UCP3 genes lower metabolic rate by a more efficient energy coupling in the mitochondria. Furthermore, genetically engineered mice over expressing different UCP homologues are lean and resistant to diet-induced obesity. The three uncoupling protein homologue genes UCP1, UCP2, and UCP3 have been investigated for polymorphisms and mutations and their impact on Type II diabetes mellitus, obesity, and body weight gain or BMI. The main conclusion is that variation in the UCP1, UCP2 or UCP3 genes is not associated with major alterations of body weight gain. The contribution of UCP genes towards polygenic obesity and Type II diabetes is evaluated and discussed.