Chronic Mealtime Shift Disturbs Metabolic and Urinary Functions in Mice: Effects of Daily Antioxidant Supplementation

Abstract

Purpose: Through their biological clocks, organisms on this rotating planet can coordinate physiological processes according to the time of the day. However, the prevalence of circadian rhythm disorders has increased in modern society with the growing number of shift workers, elevating the risk of various diseases. In this study, we employed a mouse model to investigate the effects of urinary rhythm disturbances resulting from dietary changes commonly experienced by night shift workers.Methods: We established 3 groups based on feeding time and the use of restricted feeding: ad libitum, daytime, and early nighttime feeding. We then examined the urinary rhythm in each group. In addition to the bladder rhythm, we investigated changes in mRNA patterns within the tissues constituting the bladder. Additionally, we assessed the urination rhythm in Per1 and Per2 double-knockout mice and evaluated whether the injection of antioxidants modified the impact of mealtime shift on urination rhythm in wild-type mice.Results: Our study revealed that a shift in mealtime significantly impacted the circadian patterns of water intake and urinary excretion. In Per2::Luc knock-in mouse bladders cultured ex vivo, this shift increased the amplitude of Per2 oscillation and delayed its acrophases by several hours. Daily supplementation with antioxidants did not influence the mealtime shift-induced changes in circadian patterns of water intake and urinary excretion, nor did it affect the modified Per2 oscillation patterns in the cultured bladder. However, in aged mice, antioxidants partially restored the urinary rhythm.Conclusions: A shift in mealtime meaningfully impacted the urination rhythm in mice, regardless of the presence of circadian clock genes.