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

A. D. Laposky, M. A. Bradley, D. L. Williams, J. Bass, F. W. Turek

Research output: Contribution to journalArticlepeer-review

116 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)R2059-R2066
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number6
StatePublished - Dec 2008


  • Energy metabolism
  • Metabolic syndrome
  • Sleep deprivation
  • Sleep fragmentation
  • Sleep homeostasis

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology


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