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要旨:
Shiftwork is associated with adverse metabolic pathophysiology, and the rising incidence of shiftwork in modern societies is
thought to contribute to the worldwide increase in obesity and metabolic syndrome. The underlying mechanisms are
largely unknown, but may involve direct physiological effects of nocturnal light exposure, or indirect consequences of
perturbed endogenous circadian clocks. This study employs a two-week paradigm in mice to model the early molecular and
physiological effects of shiftwork. Two weeks of timed sleep restriction has moderate effects on diurnal activity patterns,
feeding behavior, and clock gene regulation in the circadian pacemaker of the suprachiasmatic nucleus. In contrast,
microarray analyses reveal global disruption of diurnal liver transcriptome rhythms, enriched for pathways involved in
glucose and lipid metabolism and correlating with first indications of altered metabolism. Although altered food timing
itself is not sufficient to provoke these effects, stabilizing peripheral clocks by timed food access can restore molecular
rhythms and metabolic function under sleep restriction conditions. This study suggests that peripheral circadian
desynchrony marks an early event in the metabolic disruption associated with chronic shiftwork. Thus, strengthening the
peripheral circadian system by minimizing food intake during night shifts may counteract the adverse physiological
consequences frequently observed in human shift workers.
