Time-Restricted Feeding in Mice Prevents the Disruption of the Peripheral Circadian Clocks and Its Metabolic Impact during Chronic Jetlag

Abstract

We used time-restricted feeding (TRF) to investigate whether microbial metabolites and the hunger hormone ghrelin can become the dominant entraining factor during chronic jetlag to prevent disruption of the master and peripheral clocks, in order to promote health. Therefore, hypothalamic clock gene and Agrp/Npy mRNA expression were measured in mice that were either chronically jetlagged and fed ad libitum, jetlagged and fed a TRF diet, or not jetlagged and fed a TRF diet. Fecal short-chain fatty acid (SCFA) concentrations, plasma ghrelin and corticosterone levels, and colonic clock gene mRNA expression were measured. Preventing the disruption of the food intake pattern during chronic jetlag using TRF restored the rhythmicity in hypothalamic clock gene mRNA expression of Reverbα but not of Arntl. TRF countered the changes in plasma ghrelin levels and in hypothalamic Npy mRNA expression induced by chronic jetlag, thereby reestablishing the food intake pattern. Increase in body mass induced by chronic jetlag was prevented. Alterations in diurnal fluctuations in fecal SCFAs during chronic jetlag were prevented thereby re-entraining the rhythmic expression of peripheral clock genes. In conclusion, TRF during chronodisruption re-entrains the rhythms in clock gene expression and signals from the gut that regulate food intake to normalize body homeostasis.

Chronic jetlag reprograms gene expression in the colonic smooth muscle layer inducing diurnal rhythmicity in the effect of bile acids on colonic contractility

“…Further, we have previously shown that restoration of the rhythm in the food intake pattern using night-time restricted feeding in mice during chronic jetlag can prevent the effect of chronodisruption on gut epithelial homeostasis. 43,44 This may provide a rationale for the beneficial effects observed with intermittent fasting which is gaining in popularity as a nutritional approach to combat the metabolic syndrome in chronodisrupted obese patients. 45,46 We believe that shift workers may benefit from a similar approach to prevent gastrointestinal symptoms since their window of caloric intake is often stretched over nearly the entire day.…”

Dietary patterns and cardiometabolic health: Clinical evidence and mechanism

“…Desmet et al. 322 demonstrated that TRF selectively prevents jet lag‐induced disruption of the central biological clock in mice and regulates the normal rhythm of food intake to prevent weight gain. This suggests that proper feeding/fasting cycles can coordinate or reshape the biological clock to regulate behavioral and metabolic rhythms.…”

“…319,320 For example, Chaix et al 321 demonstrated that TRF effectively ameliorated metabolic defects in Cry1;Cry2 (CDKO) and liver-specific Bmal1 and Rev-erbα/β-knockout mice, thereby preserving circadian rhythms in liver transcripts and nutrient-sensing pathways. Desmet et al 322 demonstrated that TRF selectively prevents jet lag-induced disruption of the central biological clock in mice and regulates the normal rhythm of food intake to prevent weight gain. This suggests that proper feeding/fasting cycles can coordinate or reshape the biological clock to regulate behavioral and metabolic rhythms.…”

The Intestinal Clock Regulates Host Metabolism through the Fiber-Dependent Microbiome and Macronutrient Transcriptome

“…On the molecular level the circadian clock consist of core clock genes forming an autoregulatory transcriptional-translational feedback loop, thereby driving circadian oscillations of genes involved in various pathways (Takahashi, 2017). While the central clock in the hypothalamus is mainly entrained by light, peripheral clocks, including pancreas, liver, adipose tissue and the gastrointestinal (GI) tract, are predominantly entrained by the timing and composition of nutrient intake (Damiola et al, 2000;Desmet et al, 2021;Pickel and Sung, 2020). These metabolic relevant organs are responsible for digestion, absorption as well as nutrient utilization in a circadian manner (Pickel and Sung, 2020).…”