Feldmann Helena M, Golozoubova Valeria, Cannon Barbara, Nedergaard Jan
The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, Stockholm, Sweden.
Cell Metab. 2009 Feb;9(2):203-9. doi: 10.1016/j.cmet.2008.12.014.
As original studies of UCP1-ablated mice failed to demonstrate an obesogenic effect, alternative mechanisms for adaptive adrenergic thermogenesis have been sought. However, we demonstrate here that in C57Bl6 mice exempt from thermal stress (i.e., kept at thermoneutrality), UCP1 ablation in itself induced obesity, even in mice fed control diet, and vastly augmented diet-induced obesity (high-fat diet); i.e., the mice exhibited increased metabolic efficiency. In wild-type mice, high-fat diet increased norepinephrine-induced thermogenesis; i.e., diet-induced thermogenesis was observed, but no such effect was observed in UCP1-ablated mice, demonstrating that diet-induced thermogenesis fully emanates from UCP1 activity. We conclude that ambient temperature is qualitatively determinative for the outcome of metabolic studies, that no other protein and no other mechanism can substitute for UCP1 in mediating diet-induced adrenergic thermogenesis, and that UCP1 activity can be determinative for obesity development in mice and possibly in humans.
由于对UCP1基因敲除小鼠的原始研究未能证明其具有致肥胖作用，因此人们一直在寻找适应性肾上腺素能产热的替代机制。然而，我们在此证明，在不受热应激影响（即保持在热中性状态）的C57Bl6小鼠中，UCP1基因敲除本身就会导致肥胖，即使是喂食对照饮食的小鼠也是如此，并且极大地加剧了饮食诱导的肥胖（高脂饮食）；也就是说，这些小鼠表现出代谢效率提高。在野生型小鼠中，高脂饮食会增加去甲肾上腺素诱导的产热；即观察到饮食诱导的产热，但在UCP1基因敲除小鼠中未观察到这种效应，这表明饮食诱导的产热完全源于UCP1的活性。我们得出结论，环境温度在代谢研究结果中具有定性决定性，在介导饮食诱导的肾上腺素能产热过程中，没有其他蛋白质和其他机制可以替代UCP1，并且UCP1活性可能对小鼠乃至人类的肥胖发展具有决定性作用。
