Tuned by time: the role of circadian rhythms in metabolic energy sensing and chronotherapy.

INTRODUCTION

Circadian rhythms are produced endogenously from oscillators that are based on transcription-translation feedback loops, which can synchronize central and peripheral clocks into orderly timing of physiological processes to ensure the precision of metabolic homeostasis in organ such as liver, muscle, pancreas and adipose tissue. The master circadian clock located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus receives light signals and synchronizes the other internal clocks in important metabolic organs. Nuclear receptors regulate the circadian secretion of hormones and AMP-activated protein kinase (AMPK) and Sirtuins (SIRTs) represent favoured energy-sensing mechanisms in these tissue-specific clocks. This review summarizes the interplay between circadian rhythms and metabolism as well how a restoration of the circadian mechanism with the use of targeted treatments benefiting the metabolic dysfunction of a world with lengthened light exposure.

DISCUSSION: Lifestyle habits of contemporary life such as artificial light at night (ALAN) and irregular feeding regime disturb these important oscillations and interfere with physiological function and metabolism. As a result, peripheral clocks become decoupled from light-dark cycle and influence glucose absorption into the muscles. Among the disruptions, the underlying molecular mechanism includes intricate interactions among core clock genes (CLOCK, BMAL1, CRY, PER), regulation of the NAD+/NADH ratio and the lactate shuttle. Time is therefore a critical variable in the context of homeostasis as witnessed by such processes as circadian entrainment and metabolic flux. Novel chrono therapeutics are required to restore the circadian homeostasis, including time-restricted feeding, light and pharmacotherapy that responds to the circadian rhythm, in the aim of improving metabolic parameters.

CONCLUSION

Findings suggest that circadian disruption has a significant causal role in the development of metabolic disease in modern civilization. Chronotherapeutic strategies to enhance therapeutic efficacy and decrease adverse reactions by aligning treatment to an individual's time of circadian sensitivity represent one approach for restoring circadian homeostasis to remedy the ills of the modern illuminated world.