Introduction Being able to monitor the timing of biological clocks in shift workers and assess the degree of circadian misalignment between these tissue clocks, the external environment and the mistimed behaviour (e.g. sleep and feeding) remains one of the challenges in shift work research. The circadian timing system compromises the light-entrainable central oscillator, located in the hypothalamic suprachiasmatic nuclei (SCN), and peripheral clocks in almost all body tissues. Different shift work schedules result in changing light/dark; sleep/wake; and feeding/fasting patterns that differentially affect the timing of these biological clocks.

Methods Using metabolic profiling (metabolomics) we have characterised time of day variation and the effect of sleep deprivation on the human metabolome1,2 providing a baseline for future metabolomics studies in shift workers.

Results Following simulated shift work, we found profound misalignment (12 h) of many plasma metabolite rhythms3. For >90% of the metabolites, their 24-h rhythmicity was not locked to the central SCN circadian clock, rather, their rhythms aligned with the behavioural timing of the prior 3-day simulated shift schedule.

Conclusions These findings provide a window onto metabolic pathways potentially involved in the elevated risk of metabolic disorders in shift work. Metabolic profiling provides a novel way to assess the effects of mistimed sleep/wake and feeding/fasting schedules on metabolic pathways and investigate the underlying mechanisms linking metabolic disease, circadian misalignment and sleep deprivation.

1. Davies SK et al., Effect of sleep deprivation on the human metabolome. Proc Natl Acad Sci USA (2014) 111, 10761–10766; 2. Honma A et al., Effect of acute total sleep deprivation on plasma melatonin, cortisol and metabolite rhythms in females. Eur J Neurosci (2020) 51, 366–378; 3. Skene DJ et al., Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism. Proc Natl Acad Sci USA (2018) 115, 7825–7830.