Sleep-wake regulation is altered in leptin-resistant ( db/db ) genetically obese and diabetic mice
Open accessAbstract
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.
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Metabolic dysfunction, altered hormone levels, and sleep abnormalities probably all influence each other.
“In summary, metabolic dysfunction, altered hormone levels, and sleep abnormalities probably all influence each other.156,157”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [157]
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Research works printed but not linked: 2
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- Authors
- Laposky, A. D., Bradley, M. A., Williams, D. L., Bass, J., & Turek, F. W.
- Affiliations
- Northwestern University (US)
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2008-12
- Volume
- 295
- Issue
- 6
- Pages
- R2059-R2066
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- PMC
- PMC2685290
- OpenAlex
- W2138330700
- Cited by
- 135
- References
- 41
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 7 · 2023: 8 · 2022: 8 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 6 · 2017: 4 · 2016: 11 · 2015: 7 · 2014: 4 · 2013: 10 · 2012: 8
- FWCI
- 6.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P01-AG11412., P01AG011412)
- National Heart, Lung, and Blood Institute (R01HL075020)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- sleep-wake regulation, leptin resistance, db/db mice, leptin receptor, obesity, diabetes mellitus, sleep fragmentation, REM sleep, EEG delta power, sleep homeostasis, sleep deprivation, locomotor activity, circadian rhythm, energy metabolism
- MeSH terms
- Animals, Behavior, Animal, Circadian Rhythm, Diabetes Mellitus, Disease Models, Animal, Electroencephalography, Electromyography, Energy Metabolism, Male, Mice, Obese, Motor Activity, Mutation, Obesity, Phenotype, Sleep, Sleep Deprivation, Wakefulness, Signal Transduction, Recovery of Function, Leptin, Mice, Receptors, Leptin
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