Metabolic implications of circadian disruption

Abstract

Circadian rhythms are generated by the circadian clock, a self-sustained internal timing system that exhibits 24-h rhythms in the body. In mammals, circadian rhythms are driven by a central clock located in suprachiasmatic nucleus and various peripheral clocks located in different tissues and organs of the body. Many cellular, behavioral, and physiological processes are regulated by the circadian clock in coordination with environmental cues. The process of metabolism is also under circadian regulation. Loss of synchronization between the internal clock and environmental zeitgebers results in disruption of the circadian rhythms that seriously impacts metabolic homeostasis leading to changed eating behavior, altered glucose and lipid metabolism, and weight gain. This in turn augments the risk of having various cardio-metabolic disorders such as obesity, diabetes, metabolic syndrome, and cardiovascular disease. This review sheds light on circadian rhythms and their role in metabolism with the identification of gaps in the current knowledge that remain to be explored in these fields. In this review, the molecular mechanisms underlying circadian rhythms have been elaborated first. Then, the focus has been kept on explaining the physiological significance of circadian rhythms in regulating metabolism. Finally, the implications for metabolism when these rhythms are disrupted due to genetic mutations or social and occupational needs enforced by modern lifestyle have been discussed.

Keywords: Circadian rhythms; Clock genes; Gut microbiota; Metabolic disorders; Metabolism; Shift-work.