Abstract

In modern society, growing numbers of people are engaged in various forms of shift works or trans-meridian travels. Such circadian misalignment is known to disturb endogenous diurnal rhythms, which may lead to harmful physiological consequences including metabolic syndrome, obesity, cancer, cardiovascular disorders, and gastric disorders as well as other physical and mental disorders. However, the precise mechanism(s) underlying these changes are yet unclear. The present work, therefore examined the effects of 6 h advance or delay of usual meal time on diurnal rhythmicities in home cage activity (HCA), body temperature (BT), blood metabolic markers, glucose homeostasis, and expression of genes that are involved in cholesterol homeostasis by feeding young adult male mice in a time-restrictive manner. Delay of meal time caused locomotive hyperactivity in a significant portion (42%) of subjects, while 6 h advance caused a torpor-like symptom during the late scotophase. Accordingly, daily rhythms of blood glucose and triglyceride were differentially affected by time-restrictive feeding regimen with concurrent metabolic alterations. Along with these physiological changes, time-restrictive feeding also influenced the circadian expression patterns of low density lipoprotein receptor (LDLR) as well as most LDLR regulatory factors. Strikingly, chronic advance of meal time induced insulin resistance, while chronic delay significantly elevated blood glucose levels. Taken together, our findings indicate that persistent shifts in usual meal time impact the diurnal rhythms of carbohydrate and lipid metabolisms in addition to HCA and BT, thereby posing critical implications for the health and diseases of shift workers.

Highlights

  • Life on this rotating planet is confronted with periodic changes in environmental conditions

  • Both body temperature (BT) and home cage activity (HCA) rhythms were dramatically altered by time-restrictive feeding regimens (Figure 2 & 3), and two-way analysis of variance (ANOVA) revealed that these altered daily rhythms of BT and HCA are the results of interactions between the feeding schedule and zeitgeber time (Table 1)

  • The changes in BT and HCA rhythms induced by time-restrictive feeding seemed quite reversible as normal BT and HCA rhythms were recovered within a week when they returned to being fed ad libitum (Figure 2A & 3A)

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Summary

Introduction

Life on this rotating planet is confronted with periodic changes in environmental conditions. Some of the environmental changes, such as environmental illumination, temperature, food/ predator availability, are quite predictable throughout a day/night cycle. Virtually all organisms on Earth have successfully evolved endogenous mechanisms that allow organisms to harmonize their behavioral and physiological processes according to time of day. The resulting circadian rhythms are believed to optimize energy utilization, reproduction and survival [1,2]. The importance of endogenous circadian rhythms becomes evident when they are disrupted. Genetic defects within the core clock genes or circadian disturbances has been linked to various pathologies including obesity, metabolic syndrome, cancer, cardiovascular diseases, gastric disorders, and other physical and mental problems [3,4,5]

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