Torpor in mice is induced by both leptin-dependent and -independent mechanisms
Torpor in mice is induced by both leptin-dependent and -independent mechanisms
复制标题
DOI：
10.1073/pnas.96.25.14623
复制
发表时间：
1999-12-07
影响因子：
11.1
通讯作者：
Reitman, ML
中科院分区：
文献类型：
--
作者：
Gavrilova, O;Leon, LR;Reitman, ML
我们测试了慢性瘦素治疗对瘦素缺乏的A-ZIP/F-1和ob/ob小鼠禁食引起的迟钝的影响。A-ZIP/F-1小鼠几乎没有白色脂肪组织，瘦素水平低。而ob/ob小鼠有丰富的脂肪，但没有瘦素。这两个模型使我们能够检查脂肪组织和瘦素在调节进入睡眠状态中的作用。冬眠是一种短期的类似冬眠的状态，可以保存代谢燃料。我们首先描述了a - zip /F-1动物，它们体内甘油三酯的总储存减少了10倍。禁食后，a- zip /F-1小鼠代谢率降低，血糖、胰岛素和甘油三酯水平降低，游离脂肪酸或β -羟基丁酸没有增加。与对照组小鼠不同，禁食24小时后，它们的甘油三酯几乎耗尽，并开始分解代谢蛋白质。在禁食期间保存能量供应。a - zip /F-1小鼠（对照组除外）进入深度麻木状态，核心体温最低为24℃，比环境温度高2℃。在ob/ob小鼠中，瘦素治疗完全逆转了禁食引起的麻木。相比之下，瘦素和甲状腺激素都不能预防A-ZIP/F-1小鼠的麻木。这些数据表明，小鼠进入冬眠状态至少有两个信号，一个是低瘦素水平，另一个是独立于瘦素和甲状腺激素水平的信号。研究啮齿类动物的冬眠可以让我们深入了解人类类似冬眠的状态，比如在冷水中几乎溺水，以及在手术中诱发体温过低。
We tested the effect of chronic leptin treatment on fasting-induced torpor in leptin-deficient A-ZIP/F-1 and ob/ob mice. A-ZIP/F-1 mice have virtually no white adipose tissue and low leptin levels. whereas ob/ob mice have an abundance of fat but no leptin. These two models allowed us to examine the roles of adipose tissue and leptin in the regulation of entry into torpor. Torpor is a short-term hibernation-like state that allows conservation of metabolic fuels. We first characterized the A-ZIP/F-1 animals, which have a 10-fold reduction in total body triglyceride stores. Upon fasting, A-ZIP/F-1 mice develop a lower metabolic rate and decreased plasma glucose, insulin, and triglyceride levels, with no increase in free fatty acids or beta-hydroxybutyrate. Unlike control mice, by 24 hr of fasting, they have nearly exhausted their triglycerides and are catabolizing protein. To conserve energy supplies during fasting. A-ZIP/F-1 (but not control) mice entered deep torpor, with a minimum core body temperature of 24 degrees C, 2 degrees C above ambient. In ob/ob mice, fasting-induced torpor was completely reversed by leptin treatment. In contrast, neither leptin nor thyroid hormone prevented torpor in A-ZIP/F-1 mice. These data suggest that there are at least two signals for entry into torpor in mice, a low leptin level and another signal that is independent of leptin and thyroid hormone levels. Studying rodent torpor provides insight into human torpor-like states such as near drowning in cold water and induced hypothermia for surgery.