Department of Neuroscience and Neurodegeneration, Control Research Center, Kyung Hee University, Seoul, Korea.
PLoS One. 2012;7(8):e44053. doi: 10.1371/journal.pone.0044053. Epub 2012 Aug 27.
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.
在现代社会，越来越多的人从事各种形式的轮班工作或跨时区旅行。这种昼夜节律失调已知会扰乱内源性昼夜节律，可能导致有害的生理后果，包括代谢综合征、肥胖、癌症、心血管疾病和胃疾病以及其他身心障碍。然而，这些变化的确切机制尚不清楚。因此，本研究通过限时喂养的方式，研究了通常用餐时间提前或延迟 6 小时对雄性年轻成年小鼠笼内活动（HCA）、体温（BT）、血液代谢标志物、葡萄糖稳态以及参与胆固醇稳态的基因表达的昼夜节律性的影响。用餐时间的延迟导致了 42%的研究对象出现明显的运动过度，而 6 小时的提前则导致在暗光期后期出现类似昏睡的症状。因此，限时喂养方案对血糖和甘油三酯的昼夜节律有不同的影响，同时伴随着代谢改变。除了这些生理变化，限时喂养还影响了低密度脂蛋白受体（LDLR）以及大多数 LDLR 调节因子的昼夜表达模式。值得注意的是，习惯性用餐时间的持续变化会导致胰岛素抵抗，而慢性延迟则显著升高血糖水平。综上所述，我们的研究结果表明，习惯性用餐时间的持续变化会影响碳水化合物和脂质代谢的昼夜节律，以及 HCA 和 BT，这对轮班工作者的健康和疾病具有重要意义。
