Time of Day and Nutrients in Feeding Govern Daily Expression Rhythms of the Gene for Sterol Regulatory Element-binding Protein (SREBP)-1 in the Mouse Liver
Time of Day and Nutrients in Feeding Govern Daily Expression Rhythms of the Gene for Sterol Regulatory Element-binding Protein (SREBP)-1 in the Mouse Liver
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DOI：
10.1074/jbc.m109.089391
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发表时间：
2010-10-22
影响因子：
4.8
通讯作者：
Takiguchi, Masaki
中科院分区：
文献类型：
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作者：
Matsumoto, Eriko;Ishihara, Akinori;Takiguchi, Masaki
甾醇调节元件结合蛋白-1 (SREBP-1) 在肝脏脂质合成基因的转录调节中发挥核心作用，肝脏脂质合成利用饮食来源的营养物质，如碳水化合物和氨基酸，并且 SREBP-1 的表达表现出每日节律，在小鼠标准饲养条件下，在夜间进食期达到峰值。在这里，我们报告说，Srebp-1 表达节律显示出时间线索无关和时钟突变敏感的昼夜节律性质，并且显然通过运动活动和食物摄入的夹带与不同的光周期同步。禁食导致 Srebp-1 表达减少，而糖尿病 db/db 和 ob/ob 小鼠则表现出持续高表达，但节律性丧失。中光和中暗时段的限时喂食表现出不同的效果，后者会导致更严重的振荡阻尼。因此，“一天中什么时候吃东西（光/暗周期）”，而不是“一天中什么时候吃东西”，是塑造 Srebp-1 表达每日节律的关键决定因素。我们进一步发现，高碳水化合物饮食和高蛋白饮食以及高脂肪饮食会导致振荡峰相移至光期，强调“吃什么”的重要性。 SREBP-1 蛋白水平和 Akt 磷酸化水平的每日节律也表现出营养反应性变化。总而言之，这些发现提供了一个机制模型，通过该机制，一天中的时间和喂养中的营养物质塑造了 Srebp-1 表达的每日节律，并可能影响人类和野生动物的许多其他生理功能，这些生理功能具有个体间和每日间的差异，受到饮食时间和营养物质每日变化的影响。
Sterol regulatory element-binding protein-1 (SREBP-1) plays a central role in transcriptional regulation of genes for hepatic lipid synthesis that utilizes diet-derived nutrients such as carbohydrates and amino acids, and expression of SREBP-1 exhibits daily rhythms with a peak in the nocturnal feeding period under standard housing conditions of mice. Here, we report that the Srebp-1 expression rhythm shows time cue-independent and Clock mutation-sensitive circadian nature, and is synchronized with varied photoperiods apparently through entrainment of locomotor activity and food intake. Fasting caused diminution of Srebp-1 expression, while diabetic db/db and ob/ob mice showed constantly high expression with loss of rhythmicity. Time-restricted feedings during mid-light and mid-dark periods exhibited differential effects, the latter causing more severe damping of the oscillation. Therefore, "when to eat in a day (the light/dark cycle)," rather than "whenever to eat in a day," is a critical determinant to shape the daily rhythm of Srebp-1 expression. We further found that a high-carbohydrate diet and a high-protein diet, as well as a high-fat diet, cause phase shifts of the oscillation peak into the light period, underlining the importance of "what to eat." Daily rhythms of SREBP-1 protein levels and Akt phosphorylation levels also exhibited nutrient-responsive changes. Taken together, these findings provide a model for mechanisms by which time of day and nutrients in feeding shape daily rhythms of the Srebp-1 expression and possibly a number of other physiological functions with interindividual and interdaily differences in human beings and wild animals subjected to day-by-day changes in dietary timing and nutrients.