Paradoxical resistance to diet-induced obesity in UCP1-deficient mice.
Paradoxical resistance to diet-induced obesity in UCP1-deficient mice.
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DOI：
10.1172/jci15737
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发表时间：
2003-02
期刊：
影响因子：
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通讯作者：
Xiaotuan Liu;M. Rossmeisl;Jennifer W. Mcclaine;M. Riachi;M. Harper;L. Kozak
中科院分区：
文献类型：
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作者：
Xiaotuan Liu;M. Rossmeisl;Jennifer W. Mcclaine;M. Riachi;M. Harper;L. Kozak
缺乏线粒体解偶联蛋白UCP 1的小鼠的可用性提供了一个机会，以分析响应高脂肪，高糖饮食的能量消耗能力和肥胖症的发展之间的关系。与野生型小鼠相比，具有C57 BL/6 J遗传背景的同类UCP 1缺陷小鼠对饮食诱导的肥胖表现出温度依赖性抗性。这种电阻在20摄氏度时出现，当环境温度升高到27摄氏度时会迅速反转。在20 ℃时，突变型和野生型小鼠的总耗氧量和体力活动无法区分;然而，UCP 1缺陷型小鼠的体温高出0.1-0.3 ℃，呼吸商略有降低。降低的呼吸商，以及升高的β-羟基丁酸和降低的血浆脂肪酸水平，表明突变体比野生型小鼠氧化更大比例的脂肪，这可能是对饮食诱导的肥胖的抵抗。虽然颤抖是一种可能用于UCP 1缺陷小鼠的产热机制，但是否还有其他机制仍有待确定。然而，我们的研究强调了一个矛盾，即消除动物中主要的产热机制会降低而不是增加代谢效率。我们认为，在没有非颤抖性产热的情况下，必须使用替代的、热量成本更高的代谢途径来维持体温。
The availability of mice lacking the mitochondrial uncoupling protein UCP1, has provided an opportunity to analyze the relationship between the capacity for energy expenditure and the development of obesity in response to a high-fat, high-sucrose diet. Congenic UCP1-deficient mice on a C57BL/6J genetic background show a temperature-dependent resistance to diet-induced obesity when compared with wild-type mice. This resistance, which occurs at 20 degrees C, is quickly reversed when the ambient temperature is increased to 27 degrees C. At 20 degrees C, total oxygen consumption and physical activity of mutant and wild-type mice are indistinguishable; however, body temperature is higher in UCP1-deficient mice by 0.1-0.3 degrees C, and respiratory quotient is slightly reduced. A reduced respiratory quotient, together with elevated beta-hydroxybutyrate and reduced plasma fatty acid levels, suggests that the mutants oxidize a greater proportion of fat than wild-type mice, and that this possibly accounts for the resistance to diet-induced obesity. Although shivering is one alternative mechanism of thermogenesis that is probably used in UCP1-deficient mice, whether there are others remains to be determined. Nevertheless, our study underscores the paradox that elimination of the major thermogenic mechanism in the animal reduces rather than increases metabolic efficiency. We propose that in the absence of nonshivering thermogenesis, alternative, calorically more costly pathways of metabolism must be used to maintain body temperature.