The Sleep/Wake Cycle is Directly Modulated by Changes in Energy Balance.
The rise in obesity has been paralleled by a decline in sleep duration in epidemiological studies. However, the potential mechanisms linking energy balance and the sleep/wake cycle are not well understood. We aimed to examine the effects of manipulating energy balance on the sleep/wake cycle.



Twelve healthy normal weight men were housed in a clinical research facility and studied at three time points: baseline, after energy balance was disrupted by 2 days of caloric restriction to 10% of energy requirements, and after energy balance was restored by 2 days of ad libitum/free feeding. Sleep architecture, duration of sleep stages, and sleep-associated respiratory parameters were measured by polysomnography.



Two days of caloric restriction significantly increased the duration of deep (stage 4) sleep (16.8% to 21.7% of total sleep time; P = 0.03); an effect which was entirely reversed upon free feeding (P = 0.01). Although the apnea-hypopnea index stayed within the reference range (< 5 events per hour), it decreased significantly from caloric restriction to free feeding (P = 0.03). Caloric restriction was associated with a marked fall in leptin (P < 0.001) and insulin levels (P = 0.002). The fall in orexin levels from baseline to caloric restriction correlated positively with duration of stage 4 sleep (Spearman rho = 0.83, P = 0.01) and negatively with the number of awakenings in caloric restriction (Spearman rho = -0.79, P = 0.01).



We demonstrate that changes in energy homeostasis directly and reversibly impact on the sleep/wake cycle. These findings provide a mechanistic framework for investigating the association between sleep duration and obesity risk.
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science and the NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, UK.
Tinh-Hai
TH
Collet
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science and the NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, UK.
Agatha A
AA
van der Klaauw
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science and the NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, UK.
Elana
E
Henning
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science and the NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, UK.
Julia M
JM
Keogh
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science and the NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, UK.
Diane
D
Suddaby
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science and the NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, UK.
Sekesai V
SV
Dachi
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science and the NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, UK.
Síle
S
Dunbar
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science and the NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, UK.
Sarah
S
Kelway
Institute for Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden.
Suzanne L
SL
Dickson
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science and the NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, UK.
I Sadaf
IS
Farooqi
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science and the NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, UK.|Department of Internal Medicine, University of Lübeck, Germany.
Sebastian M
SM
Schmid
D000328:Adult; D031204:Caloric Restriction; D004734:Energy Metabolism / Q000502:physiology*; D064368:Healthy Volunteers; D006706:Homeostasis; D006801:Humans; D008297:Male; D009765:Obesity / Q000209:etiology; D017286:Polysomnography; D012890:Sleep / Q000502:physiology*; D012894:Sleep Stages / Q000502:physiology; D013997:Time Factors
caloric restriction; leptin; orexin; sleep