Modulation of the sleep–wake cycle by changes in energy balance

Abstract

BackgroundThe rise in obesity has been paralleled by a decline in sleep duration according to results of epidemiological studies over the past 30 years. The potential mechanisms linking energy balance and the sleep–wake cycle are not well understood. We aimed to directly assess the effects of manipulating energy balance on the sleep–wake cycle. MethodsThe study included 12 healthy normal weight men. All assessments were done at baseline, after 2 days of caloric restriction to about 200 calories per day, and after 2 days of free feeding to restore energy balance. We measured energy balance with indirect calorimetry; the sleep–wake cycle (total sleep time [TST] and time spent in various stages of sleep [%TST]); the apnoea–hypopnoea index, a marker of hypoventilation, with polysomnography; and serum leptin, insulin, and orexin concentrations. Data are given as mean (SD). FindingsThe energy deficit induced by acute caloric restriction was fully compensated for after 2 days of free feeding when energy balance was restored. Caloric restriction significantly increased the duration of deep (stage 4) sleep (from 16·8 %TST [1·8] at baseline to 21·7 [1·8] during caloric restriction, p=0·03), which was entirely reversed to 16·1 (1·9) upon free feeding (p=0·01). The apnoea–hypopnoea index was increased from 1·5 (0·5) at baseline to 2·2 (0·7) during caloric restriction and returned to baseline values upon free feeding (1·1 [0·2], p=0·05). Caloric restriction was associated with a significant fall in leptin (from 3·35 ng/mL [2·06] to 0·70 [0·52], p=0·002) and insulin concentrations (from 45·6 pmol/L [19·7] to 16·1 [9·2], p=0·005); the change in orexin concentrations from baseline to caloric restriction correlated positively with duration of stage 4 sleep in caloric restriction (Pearson r=0·71, p=0·03). Changes in energy balance also led to changes in sympathetic tone and the pulsatile secretion of thyroid stimulating hormone and growth hormone. InterpretationWe have demonstrated that changes in energy homoeostasis 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. FundingWellcome Trust, National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council, Bernard Wolfe Health Neuroscience Fund, Swiss National Science Foundation, European Society of Endocrinology, German Research Foundation, European Union Seventh Framework programme NeuroFAST consortium.