UCP1 Ablation Induces Obesity and Abolishes Diet-induced Thermogenesis in Mice Exempt from Thermal Stress by Living at Thermoneutrality
UCP1 Ablation Induces Obesity and Abolishes Diet-induced Thermogenesis in Mice Exempt from Thermal Stress by Living at Thermoneutrality
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DOI：
10.1016/j.cmet.2008.12.014
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发表时间：
2009-02-04
期刊：
影响因子：
29
通讯作者：
Nedergaard, Jan
中科院分区：
文献类型：
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作者：
Feldmann, Helena M.;Golozoubova, Valeria;Nedergaard, Jan
由于对UCP 1消融小鼠的原始研究未能证明其致肥胖作用，因此人们正在寻找适应性肾上腺素能产热的替代机制。然而，我们在这里证明，在C57 B16小鼠免除热应激（即，保持在热中性），UCP 1消融本身诱导肥胖，甚至在喂食对照饮食的小鼠中也是如此，并且极大地增强了饮食诱导的肥胖（高脂肪饮食）;即，小鼠表现出增加的代谢效率。在野生型小鼠中，高脂饮食增加去甲肾上腺素诱导的产热;即，观察到饮食诱导的产热作用，但在UCP 1消融小鼠中没有观察到这种作用，表明饮食诱导的产热作用完全源自UCP 1活性。我们的结论是，环境温度是定性的代谢研究的结果，没有其他蛋白质，没有其他机制可以取代UCP 1在介导饮食诱导的肾上腺素能产热，UCP 1的活性可以决定在小鼠和可能在人类肥胖的发展。
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 C57B16 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.