The clockwork of metabolism

The observation that cycles of sleep and wakefulness occur with a periodicity fixed in time to match the rotation of the Earth on its axis provided a key to unlock the first genetic code for a neurobehavioral pathway in flies and ultimately in mice. As a remarkable outcome of this discovery, we have gained an unprecedented view of the conserved genetic program that encodes a sense of time across all kingdoms of life. The tools are now in hand to begin to understand how important processes such as energy homeostasis and fuel utilization are coordinated to anticipate daily changes in environment caused by the rising and setting of the sun. A better understanding of the impact of circadian gene networks on nutrient balance at the molecular, cellular, and system levels promises to shed light on the emerging association between disorders of diabetes, obesity, sleep, and circadian timing.