Abstract
Disruption to sleep and circadian rhythms can impact on metabolism. The study aimed to investigate the effect of acute sleep deprivation on plasma melatonin, cortisol and metabolites, to increase understanding of the metabolic pathways involved in sleep/wake regulation processes. Twelve healthy young female participants remained in controlled laboratory conditions for ~92 hr with respect to posture, meals and environmental light (18:00–23:00 hr and 07:00‐09:00 hr <8 lux; 23:00–07:00 hr 0 lux (sleep opportunity) or <8 lux (continuous wakefulness); 09:00–18:00 hr ~90 lux). Regular blood samples were collected for 70 hr for plasma melatonin and cortisol, and targeted liquid chromatography–mass spectrometry metabolomics. Timepoints between 00:00 and 06:00 hr for day 1 (baseline sleep), day 2 (sleep deprivation) and day 3 (recovery sleep) were analysed. Cosinor analysis and MetaCycle analysis were performed for detection of rhythmicity. Night‐time melatonin levels were significantly increased during sleep deprivation and returned to baseline levels during recovery sleep. No significant differences were observed in cortisol levels. Of 130 plasma metabolites quantified, 41 metabolites were significantly altered across the study nights, with the majority decreasing during sleep deprivation, most notably phosphatidylcholines. In cosinor analysis, 58 metabolites maintained their rhythmicity across the study days, with the majority showing a phase advance during acute sleep deprivation. This observation differs to that previously reported for males. Our study is the first of metabolic profiling in females during sleep deprivation and recovery sleep, and offers a novel view of human sleep/wake regulation and sex differences.
Highlights
Sleep comprises approximately one‐third of our lifetime and is an essential physiological function indispensable for survival
The master clock, located in the hypothalamic suprachiasmatic nuclei (SCN), is entrained to the external light–dark cycle by photic signals transmitted via the retinohypothalamic tract, and coordinates timing of peripheral clocks distributed throughout the body (Barclay et al, 2012; Reppert & Weaver, 2002)
The pineal hormone melatonin showed significantly increased plasma concentrations during sleep deprivation, which is in agreement with our previous study in young males (Ackermann et al, 2013; Davies et al, 2014), and returned to baseline levels during a subsequent night of recovery sleep
Summary
Sleep comprises approximately one‐third of our lifetime and is an essential physiological function indispensable for survival. Circadian clocks control the timing of most daily biological processes, behaviour and activity, including changes in metabolism and the sleep/wake cycle (Hastings, Reddy, & Maywood, 2003; Mohawk, Green, & Takahashi, 2012). In spite of numerous studies on sex differences in metabolic profiling (Mittelstrass et al, 2011; Rist et al, 2017; Ruoppolo et al, 2014), surprisingly little is known about the effect of sleep deprivation on metabolite profiles in females. The aim of this study was to assess the timing, amplitude and phase relationship of the SCN‐driven hormone rhythms (melatonin and cortisol) and plasma metabolite rhythms with a sleep/wake cycle, during 24 hr of wakefulness and a recovery sleep in healthy young females. Assessing the effect of acute sleep deprivation on circulating metabolites and their rhythms may lead to increased understanding of the metabolic pathways involved in sleep/ wake regulation and development of sleep biomarkers
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