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Am J Physiol Regul Integr Comp Physiol 295: R2059-R2066, 2008. First published October 8, 2008; doi:10.1152/ajpregu.00026.2008
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SLEEP AND BIOLOGICAL RHYTHMS

Sleep-wake regulation is altered in leptin-resistant (db/db) genetically obese and diabetic mice

A. D. Laposky,1,2 M. A. Bradley,1 D. L. Williams,1 J. Bass,2,3 and F. W. Turek1,2

1Department of Neurobiology and Physiology, Northwestern University, Center for Sleep and Circadian Biology; and 2Evanston Northwestern Healthcare and Research Institute, 3Department of Medicine, Evanston, Illinois

Submitted 14 January 2008 ; accepted in final form 28 September 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.

sleep fragmentation; metabolic syndrome; energy metabolism; sleep homeostasis; sleep deprivation



Address for reprint requests and other correspondence: A. D. Laposky, National Institutes of Health, NHLBI/Division of Lung Diseases, National Center for Sleep Disorders Research, 6701 Rockledge Dr., Ste. 10042, Bethesda, MD 20892 (e-mail: laposkya{at}nhlbi.nih.gov)




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