The role of cell-specific circadian clocks in metabolism and disease.

Abstract

Biological rhythms are an integral component of essentially all aspects of life. These rhythms are controlled in part by circadian clocks, transcriptionally based mechanisms that synchronize the organism to its changing environment. The central circadian clock is located within the suprachiasmatic nucleus of the brain, while peripheral clocks are located within virtually all cells outside of the suprachiasmatic nucleus. Although our understanding of central clock structure and function is well advanced, the role of peripheral clocks in whole body energy metabolism is just beginning to be elucidated. Both central and peripheral circadian clocks likely regulate many physiological functions, including insulin sensitivity, endocrine regulation, energy homeostasis, satiety signalling, cellular proliferation and cardiovascular function. Widely varying phenotypes have been reported following global genetic disruption of the clock mechanism in mice, with phenotype dependent on both the clock component targeted and genetic background. The inconsistency in phenotypes associated with clock disruption may be due, in part, to cell-specific effects of the circadian clocks. To address this question, many laboratories have begun generating animal models of cell type-specific clock disruption. In this review, we summarize the existing literature on tissue-specific models of circadian clock disruption and provide a focus for future research in this area.