Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, Republic of Korea.
Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul 03760, Republic of Korea.
Int J Mol Sci. 2024 Jul 5;25(13):7373. doi: 10.3390/ijms25137373.
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, 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 and and an advanced peak phase of . 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.
生物钟的调节在影响生理状况方面起着重要作用。虽然有报道称能量摄入的时间和数量会影响生物钟的调节，但其中的机制尚不清楚。本研究探讨了饮食蛋白质摄入对周围时钟的影响。首先，进行了转录组分析，以研究低蛋白摄入的分子靶标。其次，分析了用低蛋白、正常或高蛋白饮食喂养 6 周的 knock-in 小鼠，以研究外周组织中 PER2 表达的振荡和昼夜节律和代谢基因的表达谱。最后，使用 AML12 细胞验证了体内分析确定的候选途径。结果，通过转录组分析，我们发现低蛋白饮食几乎不会改变中央时钟的昼夜节律。在动物实验中，PER2 的表达水平和周期长度因饮食蛋白质摄入而异；此外，时钟控制基因和内质网（ER）应激基因的 mRNA 水平也受到饮食蛋白质摄入的影响。AML12 细胞中 ER 应激的诱导导致 和 的振幅增加，峰相提前。这一结果表明，不同饮食蛋白质比例的摄入会导致昼夜节律发生变化，尤其是在小鼠的外周时钟中。饮食蛋白质摄入改变了 ER 应激基因的振荡，这可能在生物钟的调节中发挥关键作用。
