Caveolin-1 expression is essential for proper nonshivering thermogenesis in brown adipose tissue
Caveolin-1 expression is essential for proper nonshivering thermogenesis in brown adipose tissue
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DOI：
10.2337/diabetes.54.3.679
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发表时间：
2005-03-01
期刊：
影响因子：
7.7
通讯作者：
Lisanti, MP
中科院分区：
文献类型：
--
作者：
Cohen, AW;Schubert, W;Lisanti, MP
最近，我们发现小窝蛋白-1的缺失导致白色脂肪组织中胰岛素信号和脂解的显著改变。然而，很少有人知道的作用，小窝蛋白-1在棕色脂肪组织（BAT），一个组织负责非颤抖产热。在这里，我们表明caveolin-1基因敲除小鼠具有轻微但显著的静息核心体温降低。为了详细研究这一点，我们接下来对小鼠进行禁食（24小时）或冷处理（4 ℃，24小时），单独或组合。有趣的是，caveolin-1基因敲除小鼠在禁食或禁食/冷处理后体温显著降低;然而，单独的冷处理没有效果。此外，在这些条件下，caveolin-1缺失小鼠未能显示由禁食或禁食/冷处理诱导的血清非脂肪酸的正常增加，表明这些小鼠不能释放甘油三酯储存用于产热。根据这些结果，在禁食/冷处理后，野生型小鼠中BAT的甘油三酯含量减少了近10倍，但在caveolin-1缺失小鼠中仅减少了3倍。最后，脂肪组织的电子显微镜显示，在线粒体的小窝蛋白-1空肩胛间棕色脂肪细胞显着扰动。总之，我们的数据提供了第一个分子遗传学证据，小窝蛋白-1通过对脂质动员的影响在调节产热中起着关键的功能和结构作用。
Recently, we have shown that loss of caveolin-1 leads to marked alterations in insulin signaling and lipolysis in white adipose tissue. However, little is known about the role of caveolin-1 in brown adipose tissue (BAT), a tissue responsible for nonshivering thermogenesis. Here, we show that caveolin-1 null mice have a mildly, yet significantly, decreased resting core body temperature. To investigate this in detail, we next subjected the mice to fasting (for 24 h) or cold treatment (4degreesC for 24 h), individually or in combination. Interestingly, caveolin-1 null mice showed markedly decreased body temperatures in response to fasting or fasting/cold treatment; however, cold treatment alone had no effect. In addition, under these conditions caveolin-1 null mice failed to show the normal increase in serum nonesterifled fatty acids induced by fasting or fasting/cold treatment, suggesting that these mice are unable to liberate triglyceride stores for heat production. In accordance with these results, the triglyceride content of BAT was reduced nearly 10-fold in wild-type mice after fasting/ cold treatment, but it was reduced only 3-fold in caveolin-1 null mice. Finally, electron microscopy of adipose tissue revealed dramatic perturbations in the mitochondria of caveolin-1 null interscapular brown adipocytes. Taken together, our data provide the first molecular genetic evidence that caveolin-1 plays a critical functional and structural role in the modulation of thermogenesis via an effect on lipid mobilization.