Woller, A.; Gonze, D. Circadian Misalignment and Metabolic Disorders: A Story of Twisted Clocks. Biology 2021, 10, 207. https://doi.org/10.3390/biology10030207AMA Style
In mammals, many physiological processes follow a 24 h rhythmic pattern. These rhythms are governed by a complex network of circadian clocks, which perceives external time cues (notably light and nutrients) and adjusts the timing of metabolic and physiological functions to allow a proper adaptation of the organism to the daily changes in the environmental conditions. Circadian rhythms originate at the cellular level through a transcriptional–translational regulatory network involving a handful of clock genes. In this review, we show how adverse effects caused by ill-timed feeding or jet lag can lead to a dysregulation of this genetic clockwork, which in turn results in altered metabolic regulation and possibly in diseases. We also show how computational modeling can complement experimental observations to understand the design of the clockwork and the onset of metabolic disorders.
Biological clocks are cell-autonomous oscillators that can be entrained by periodic environmental cues. This allows organisms to anticipate predictable daily environmental changes and, thereby, to partition physiological processes into appropriate phases with respect to these changing external conditions. Nowadays our 24/7 society challenges this delicate equilibrium. Indeed, many studies suggest that perturbations such as chronic jet lag, ill-timed eating patterns, or shift work increase the susceptibility to cardiometabolic disorders, diabetes, and cancers. However the underlying mechanisms are still poorly understood. A deeper understanding of this complex, dynamic system requires a global holistic approach for which mathematical modeling can be highly beneficial. In this review, we summarize several experimental works pertaining to the effect of adverse conditions on clock gene expression and on physiology, and we show how computational models can bring interesting insights into the links between circadian misalignment and metabolic diseases.
View Full Text: