Abstract
Simple SummaryIn 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.
Highlights
In mammals a large range of physiological and metabolic processes display a 24 h rhythmic pattern
Through a selection of experimental and theoretical papers, how the phase relationships between the clock gene expression are altered under ill-timed feeding or in response to a jet lag and how, in turn, those “twisted clocks” impact clock-controlled cellular processes
Bur et al [85] found that daytime-restricted feeding reversed the rhythmicity of clock gene expression in the liver, whereas it strongly dampened the oscillations in the pituitary gland. These authors further noticed that, in the absence of GCs, the inversion of gene expression in the liver clock following the transition from day-restricted feeding to night-restricted feeding is faster, but that the daily expression of clock genes is not affected by the feeding timing
Summary
In mammals a large range of physiological and metabolic processes display a 24 h rhythmic pattern These processes are controlled by an elaborate circadian system consisting of a finely tuned network of clocks throughout the body coupled together by periodically released hormones, nutrient sensors, and neuronal connections. Besides controlling the sleep–wake cycle, this system appears to be optimized to ensure metabolic homeostasis (by allowing anticipation of food uptake), an effective immune response, and synchronized cell division [1,2]. It relies on the alignment of the light–dark cycle and the feeding–fasting pattern and on a precise genetic clockwork. Through a selection of experimental and theoretical papers, how the phase relationships between the clock gene expression are altered under ill-timed feeding or in response to a jet lag and how, in turn, those “twisted clocks” impact clock-controlled cellular processes
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