Dept. of Physiology, Wenner-Gren Institute, Stockholm Univ., Sweden.
Am J Physiol Endocrinol Metab. 2010 Sep;299(3):E374-83. doi: 10.1152/ajpendo.00071.2010. Epub 2010 Jun 8.
Caveolin-1 (Cav1)-ablated mice display impaired lipolysis in white adipose tissue. They also seem to have an impairment in brown adipose tissue function, implying that Cav1-ablated mice could encounter problems in surviving longer periods in cold temperatures. To investigate this, Cav1-ablated mice and wild-type mice were transferred to cold temperatures for extended periods of time, and parameters related to metabolism and thermogenesis were investigated. Unexpectedly, the Cav1-ablated mice survived in the cold. There were no differences between Cav1-ablated and wild-type mice with regard to food intake, in behavior related to shivering, or in body temperature. The Cav1-ablated mice had a halved total fat content independently of acclimation temperature. There was no difference in brown adipose tissue uncoupling protein-1 (UCP1) protein amount, and isolated brown fat mitochondria were thermogenically competent but displayed 30% higher thermogenic capacity. However, the beta(3)-adrenergic receptor amount was reduced by about one-third in the Cav1-ablated mice at all acclimation temperatures. Principally in accordance with this, a higher than standard dose of norepinephrine was needed to obtain full norepinephrine-induced thermogenesis in the Cav1-ablated mice; the higher dose was also needed for the Cav1-ablated mice to be able to utilize fat as a substrate for thermogenesis. In conclusion, the ablation of Cav1 impairs brown adipose tissue function by a desensitization of the adrenergic response; however, the desensitization is not evident in the animal as it is overcome physiologically, and Cav1-ablated mice can therefore survive in prolonged cold by nonshivering thermogenesis.
窖蛋白-1（Cav1）敲除小鼠的白色脂肪组织脂肪分解受损。它们的棕色脂肪组织功能似乎也受损，这意味着 Cav1 敲除小鼠在寒冷环境中可能难以长时间生存。为了研究这一问题，将 Cav1 敲除小鼠和野生型小鼠转移到寒冷环境中，并研究了与代谢和产热相关的参数。出人意料的是，Cav1 敲除小鼠在寒冷中存活了下来。Cav1 敲除小鼠和野生型小鼠在食物摄入、与颤抖相关的行为或体温方面没有差异。无论适应温度如何，Cav1 敲除小鼠的总脂肪含量减少了一半。棕色脂肪组织解偶联蛋白 1（UCP1）蛋白含量无差异，分离的棕色脂肪线粒体产热能力正常，但产热能力高 30%。然而，Cav1 敲除小鼠在所有适应温度下的β3-肾上腺素能受体数量减少了约三分之一。基本上与这一结果一致，Cav1 敲除小鼠需要比标准剂量高的去甲肾上腺素才能获得完全的去甲肾上腺素诱导的产热；Cav1 敲除小鼠也需要更高的剂量才能将脂肪用作产热的底物。总之，Cav1 的缺失通过肾上腺素能反应的脱敏作用损害了棕色脂肪组织的功能；然而，这种脱敏在动物中并不明显，因为它被生理上克服了，因此 Cav1 敲除小鼠可以通过非颤抖产热在长时间的寒冷中存活。
