Clock Genes and Metabolic Regulation

The discovery of clock genes has elucidated molecular mechanisms generating circadian rhythms in all forms of life on earth. Intracellular molecular clock genes encode an autoregulatory feedback loop that comprises transcriptional activators and repressors that together oscillate with a periodicity of 24 h. In mammals, circadian rhythms of behavior and physiology are organized hierarchically; the principal clock resides within the suprachiasmatic nucleus (SCN) of the hypothalamus, setting the tempo for multiple peripheral clocks and giving rise to circadian resonance. Signals produced by SCN pacemaker neurons act both directly and indirectly to coordinate behavioral and physiological processes, including the sleep-wake cycle and energy metabolism. At the molecular level, clock genes not only generate circadian rhythms but also interact with other genes that regulate glucose and lipid metabolism. Investigation into the intersection between neuroanatomic and molecular pathways that maintain homeostatic control of both circadian biology and metabolism may lead to a better understanding of the links between circadian and sleep disorders with diabetes mellitus and obesity.