Fleury C, Neverova M, Collins S, Raimbault S, Champigny O, Levi-Meyrueis C, Bouillaud F, Seldin M F, Surwit R S, Ricquier D, Warden C H
CNRS/CEREMOD, Meudon, France.
Nat Genet. 1997 Mar;15(3):269-72. doi: 10.1038/ng0397-269.
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. This pathway has been implicated in the regulation of body temperature, body composition and glucose metabolism. 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 oxygen consumption or energy expenditure to lose or gain heat to maintain body temperature), as there is little brown adipose tissue present. We now report the discovery of a gene that codes for a novel uncoupling protein, designated UCP2, which has 59% amino-acid 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.
一种名为解偶联蛋白（UCP1）的线粒体蛋白，通过在棕色脂肪组织中创建一条允许质子电化学梯度跨线粒体内膜消散的途径，在产热和消耗卡路里方面发挥着重要作用，且不与任何其他耗能过程相偶联。该途径与体温、身体成分和葡萄糖代谢的调节有关。然而，在成年大型动物和生活在热中性环境（即动物无需增加氧气消耗或能量消耗来散热或产热以维持体温）中的人类中，含有UCP1的棕色脂肪组织不太可能参与体重调节，因为棕色脂肪组织很少。我们现在报告发现了一个编码新型解偶联蛋白的基因，命名为UCP2，它与UCP1有59%的氨基酸同一性，并描述了与糖尿病和肥胖症相关作用一致的特性。与UCP1相比，UCP2在酵母中表达时对线粒体膜电位有更大影响。与UCP1相比，该基因在成人组织中广泛表达，包括富含巨噬细胞的组织，并且在喂食脂肪后白色脂肪中表达上调。最后，UCP2定位于人类11号染色体和小鼠7号染色体上与高胰岛素血症和肥胖症相关的区域。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作用。
