Sleep-wake regulation is altered in leptin-resistant (db/db) genetically obese and diabetic mice
Sleep-wake regulation is altered in leptin-resistant (db/db) genetically obese and diabetic mice
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DOI：
10.1152/ajpregu.00026.2008
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发表时间：
2008-12-01
影响因子：
2.8
通讯作者：
Turek, F. W.
中科院分区：
文献类型：
--
作者：
Laposky, A. D.;Bradley, M. A.;Turek, F. W.
Laposky AD，布拉德利MA，威廉姆斯DL，巴斯J，图雷克FW.在瘦素抵抗（db/db）遗传性肥胖和糖尿病小鼠中，睡眠-觉醒调节发生改变。Am J Physiol Regul Integr Comp Physiol 295：R2059-R2066，2008。首次发表于2008年10月8日; doi：10.1152/ajpregu.00026.2008。最近的流行病学和临床研究表明，睡眠-觉醒状态的控制可能是调节能量代谢的重要因素。瘦素是一种外周合成的激素，在大脑中具有控制长期能量稳态的关键信号特性。在这项研究中，我们研究了瘦素信号在睡眠-觉醒调节中发挥作用的假设，瘦素可能是协调睡眠-觉醒状态和代谢的重要机制环节。睡眠-觉醒模式记录在肥胖和糖尿病的遗传小鼠模型中，db/db小鼠，其在瘦素受体的特定亚型（长型，LRb）中具有突变。我们发现db/db小鼠在睡眠调节方面表现出多种改变，包括总睡眠时间增加、睡眠片段化显著增加、快速眼动睡眠和非快速眼动EEG δ功率（睡眠稳态驱动的量度）中的昼夜节律减弱以及对急性（即，6 h）睡眠剥夺。db/db小鼠还产生少量的自发活动和活动的昼夜节律减少。这些结果表明，受损的瘦素信号对睡眠量、睡眠结构和这些唤醒状态的时间巩固的调节具有有害影响。总之，瘦素可能是睡眠、昼夜节律和能量代谢整合中的重要分子组分。
Laposky AD, Bradley MA, Williams DL, Bass J, Turek FW. Sleep-wake regulation is altered in leptin-resistant (db/db) genetically obese and diabetic mice. Am J Physiol Regul Integr Comp Physiol 295: R2059-R2066, 2008. First published October 8, 2008; doi:10.1152/ajpregu.00026.2008. -Recent epidemiological and clinical studies indicate that the control of sleep-wake states may be an important factor in the regulation of energy metabolism. Leptin is a peripherally synthesized hormone that has critical signaling properties in the brain for the control of long-term energy homeostasis. In this study, we examined the hypothesis that leptin signaling exerts a role in sleep-wake regulation and that leptin may represent an important mechanistic link in the coordination of sleep-wake states and metabolism. Sleep-wake patterns were recorded in a genetic mouse model of obesity and diabetes, the db/db mouse, which harbors a mutation in a particular isoform of the leptin receptor (long form, LRb). We found that db/db mice exhibit a variety of alterations in sleep regulation, including an increase in overall sleep time, a dramatic increase in sleep fragmentation, attenuated diurnal rhythmicity in rapid eye movement sleep and non-rapid eye movement EEG delta power ( a measure of sleep homeostatic drive), and a decrease in the compensatory response to acute (i.e., 6 h) sleep deprivation. The db/db mice also generated low amounts of locomotor activity and a reduction in the diurnal rhythm of activity. These results indicate that impaired leptin signaling has deleterious effects on the regulation of sleep amount, sleep architecture, and temporal consolidation of these arousal states. In summary, leptin may represent an important molecular component in the integration of sleep, circadian rhythms, and energy metabolism.