Uncoupling protein-2: A novel gene linked to obesity and hyperinsulinemia
Uncoupling protein-2: A novel gene linked to obesity and hyperinsulinemia
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DOI：
10.1038/ng0397-269
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发表时间：
1997-03-01
期刊：
影响因子：
30.8
通讯作者：
Warden, CH
中科院分区：
文献类型：
--
作者：
Fleury, C;Neverova, M;Warden, CH
一种名为解偶联蛋白（UCP1）的线粒体蛋白在产生热量和燃烧卡路里方面发挥着重要作用，它创建了一条途径，允许质子电化学梯度穿过棕色脂肪组织的线粒体内膜消散，而不耦合任何其他能量消耗过程(1)。这一途径与体温、身体成分和葡萄糖代谢的调节有关(2)。然而，含有ucp1的棕色脂肪组织不太可能参与成年大型动物和生活在热中性环境中的人类的体重调节（动物不需要增加消耗来降温），因为存在很少的棕色脂肪组织(3)。我们现在报告了一个基因的发现，该基因编码一种新的解偶联蛋白，称为UCP2，它与UCP1具有59%的氨基酸同源性，并且描述了与糖尿病和肥胖的作用一致的特性。与UCP1相比，UCP2在酵母中表达时对线粒体膜电位的影响更大。与UCP1相比，该基因在成人人体组织中广泛表达，包括富含巨噬细胞的组织，并且在白色脂肪中因脂肪喂养而上调。最后，UCP2映射到人类11号染色体和小鼠7号染色体上与高胰岛素血症和肥胖有关的区域。我们的研究结果表明，UCP2在能量平衡、体重调节和体温调节及其对炎症刺激的反应中具有独特的作用。
A mitochondrial protein called uncoupling protein (UCP1) plays an important role in generating heat and burning calories by creating a pathway that allows dissipation of the proton electrochemical gradient across the inner mitochondrial membrane in brown adipose tissue, without coupling to any other energy-consuming process(1). This pathway has been implicated in the regulation of body temperature, body composition and glucose metabolism(2). However, UCP1-containing brown adipose tissue is unlikely to be involved in weight regulation in adult large-size animals and humans living in a thermoneutral environment (one where an animal does not have to increase expenditure to lose temperature), as there is little brown adipose tissue present(3). We now report the discovery of a gene that codes for a novel uncoupling protein, designated UCP2, which has 59% aminoacid identity to UCP1, and describe properties consistent with a role in diabetes and obesity. In comparison with UCP1, UCP2 has a greater effect on mitochondrial membrane potential when expressed in yeast. Compared to UCP1, the gene is widely expressed in adult human tissues, including tissues rich in macrophages, and it is upregulated in white fat in response to fat feeding. Finally, UCP2 maps to regions of human chromosome 11 and mouse chromosome 7 that have been linked to hyperinsulinaemia and obesity. Our findings suggest that UCP2 has a unique role in energy balance, body weight regulation and thermoregulation and their responses to inflammatory stimuli.