Circadian metabolomics from mice and men: Insights for mechanism and medicine

A biological "circadian" clock regulates nearly all aspects of mammalian physiology in accordance with the solar day. Not only sleep and wake, but also mood and cognition, circulation and cardiac function, and nearly all aspects of digestion and detoxication are under circadian control. This diurnal programming is exerted through both hormonal and cell-autonomous mechanisms at multiple levels. For the whole organism, our laboratory has demonstrated global circadian control of the human metabolome in blood and saliva, even in the absence of diurnal sleep, wake, and food intake. Nevertheless, sleep also plays an independent role in regulating global metabolic function, because splitting the sleep-wake cycle into multiple naps decreases circadian rhythmicity beyond even that observed with total sleep deprivation. For individual tissues, we find that circadian control of metabolism and other processes plays a strong role, even in growing tumors. Finally, at a cellular level, we have shown that circadian control of the metabolome could be mediated by global control of mitochondrial morphology and function. Thus, from cells to humans, pervasive circadian control of metabolism is pervasive, and could provide clues for novel treatment strategies for diseases ranging from obesity to cancer.