Coupling the circadian clock to homeostasis: the role of Period in timing physiology.

A plethora of physiological processes show stable and synchronized daily oscillations that are either driven or modulated by biological clocks. A circadian pacemaker located in the suprachiasmatic nucleus of the ventral hypothalamus coordinates 24-hour oscillations of central and peripheral physiology with the environment. The circadian clockwork involved in driving rhythmic physiology is composed of various clock genes that are interlocked via a complex feedback loop to generate precise yet plastic oscillations of approximate to 24 hours. This review focuses on the specific role of the core clockwork gene Period1 and its paralogs on intra-oscillator and extra-oscillator functions, including, but not limited to, hippocampus-dependent processes, cardiovascular function, appetite control, as well as glucose and lipid homeostasis. Alterations in Period gene function have been implicated in a wide range of physical and mental disorders. At the same time, a variety of conditions including metabolic disorders also impact clock gene expression, resulting in circadian disruptions, which in turn often exacerbates the disease state.