Dalgaard L T, Pedersen O
Steno Diabetes Center, Gentofte, Denmark.
Diabetologia. 2001 Aug;44(8):946-65. doi: 10.1007/s001250100596.
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.
解偶联蛋白是线粒体载体蛋白，能够消除线粒体内膜的质子梯度。这种解偶联过程会减少通过燃料氧化产生的三磷酸腺苷（ATP）量。解偶联蛋白（UCPs）是人类肥胖症或II型（非胰岛素依赖型）糖尿病候选基因的这一假说，是基于线粒体膜的化学解偶联会降低身体肥胖程度这一发现，以及较低的代谢率预示体重增加这一现象。很容易推测，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了代谢率。此外，过度表达不同UCP同源物的基因工程小鼠体型瘦，且对饮食诱导的肥胖具有抗性。已经对三种解偶联蛋白同源基因UCP1、UCP2和UCP3的多态性、突变及其对II型糖尿病、肥胖症以及体重增加或体重指数（BMI）的影响进行了研究。主要结论是，UCP1、UCP2或UCP3基因的变异与体重增加的主要改变无关。对UCP基因在多基因肥胖症和II型糖尿病中的作用进行了评估和讨论。
