PDF(Pubmed)
Abstract：
The regulation of the circadian clock plays an important role in influencing physiological conditions. While it is reported that the timing and quantity of energy intake impact circadian regulation, the underlying mechanisms remain unclear. This study investigated the impact of dietary protein intake on peripheral clocks. Firstly, transcriptomic analysis was conducted to investigate molecular targets of low-protein intake. Secondly, mPer2::Luc knock-in mice, fed with either a low-protein, normal, or high-protein diet for 6 weeks, were analyzed for the oscillation of PER2 expression in peripheral tissues and for the expression profiles of circadian and metabolic genes. Lastly, the candidate pathway identified by the in vivo analysis was validated using AML12 cells. As a result, using transcriptomic analysis, we found that the low-protein diet hardly altered the circadian rhythm in the central clock. In animal experiments, expression levels and period lengths of PER2 were different in peripheral tissues depending on dietary protein intake; moreover, mRNA levels of clock-controlled genes and endoplasmic reticulum (ER) stress genes were affected by dietary protein intake. Induction of ER stress in AML12 cells caused an increased amplitude of Clock and Bmal1 and an advanced peak phase of Per2. This result shows that the intake of different dietary protein ratios causes an alteration of the circadian rhythm, especially in the peripheral clock of mice. Dietary protein intake modifies the oscillation of ER stress genes, which may play key roles in the regulation of the circadian clock.
摘要：
生物钟的调节在影响生理状况中起着重要作用。据报道，能量摄入的时间和数量影响昼夜节律调节，潜在机制尚不清楚.这项研究调查了饮食蛋白质摄入对外围时钟的影响。首先,进行转录组学分析以研究低蛋白摄入的分子靶标。其次,mPer2::Luc敲入小鼠，用低蛋白喂养，正常,或高蛋白饮食6周，分析了外周组织中PER2表达的振荡以及昼夜节律和代谢基因的表达谱。最后,通过体内分析确定的候选途径使用AML12细胞进行验证.因此,使用转录组学分析，我们发现，低蛋白饮食几乎不改变中心时钟的昼夜节律。在动物实验中,PER2的表达水平和周期长度在外周组织中不同，取决于饮食蛋白质的摄入量；此外，日粮蛋白质摄入量会影响时钟控制基因和内质网（ER）应激基因的mRNA水平。AML12细胞中ER应力的诱导导致Clock和Bmal1的振幅增加以及Per2的峰值相位提前。这一结果表明，不同膳食蛋白质比例的摄入会导致昼夜节律的改变，特别是在老鼠的外围时钟中。膳食蛋白质摄入量改变ER应激基因的振荡，这可能在昼夜节律时钟的调节中起关键作用。
