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Publication

Tuning feeding time to prevent the effects of chronodisruption in the gut induced by chronic jetlag

Book - Dissertation

The circadian system ensures that organisms can adapt their physiology to the cyclic presence of several environmental cues. When a mismatch occurs between behavioural (feeding/fasting; activity/rest) cues and the intrinsic circadian clock this system becomes disrupted, also referred to as chronodisruption. Restricting the eating window to a certain time window (time restricted feeding), can be used to realign the food intake pattern to the intrinsic circadian clock thereby preventing the detrimental effects induced by chronodisruption. The aim of this PhD thesis was to investigate in a mouse model of chronic jetlag, the impact of chronodisruption on the diurnal cycling of microbial metabolites that may affect gut homeostasis by altering rhythmicity in clock gene expression. In addition, we investigated the health promoting effects of time restricted feeding (TRF). Chronic jetlag in mice induced body weight gain and altered the food intake pattern which concurred with a phase delay in the faecal SCFAs peak and abolished the diurnal fluctuations in serum bile acid levels. As a result, the rhythm in circadian clock gene expression in both the gut mucosa and smooth muscle layer was shifted. This may have disrupted the formation of the CLOCK:ARNTL heterodimer in the gut mucosa that regulates the mRNA expression of several genes including the hunger hormone ghrelin, as shown by our findings in the Arntl-/- mice. Furthermore, we speculate that chronodisruption caused a transcriptional reprogramming in the colonic smooth muscle layer thereby inducing a rhythm in the mRNA expression of the bile acid receptor, Gpbar1. In turn, this generated a rhythm in the inhibitory effect of the secondary bile acid taurodeoxycholic acid on colonic contractility. Restoring the food intake pattern using TRF prevented body weight gain in mice with chronic jetlag. TRF countered the loss in the rhythmicity in plasma ghrelin levels and in hypothalamic Npy expression thereby reestablishing the food intake pattern. As a result, faecal SCFA levels continued to fluctuate, thereby re-entraining rhythmicity of gut clock genes. Further, food-induced cues might indirectly feedback to the central circadian clock to partially restore clock gene expression in the hypothalamus. To conclude, in this PhD thesis, we demonstrated that food becomes a dominant entraining factor in the absence of a functional master clock during chronic jetlag, driving changes in circadian clock gene expression in the gut with effects on gut hormone release and contractility. TRF, to maintain a normal food intake pattern, can be used as a paradigm to prevent certain aspects of chronodisruption induced by chronic jetlag.
Publication year:2022
Accessibility:Open