Program of Genetics, Texas A&M University, College Station, TX 77843, USA; Department of Biology, Texas A&M University, College Station, TX 77843, USA.
Department of Biology, Texas A&M University, College Station, TX 77843, USA.
Cell Rep. 2019 Apr 16;27(3):649-657.e5. doi: 10.1016/j.celrep.2019.03.064.
Every mammalian tissue exhibits daily rhythms in gene expression to control the activation of tissue-specific processes at the most appropriate time of the day. Much of this rhythmic expression is thought to be driven cell autonomously by molecular circadian clocks present throughout the body. By manipulating the daily rhythm of food intake in the mouse, we here show that more than 70% of the cycling mouse liver transcriptome loses rhythmicity under arrhythmic feeding. Remarkably, core clock genes are not among the 70% of genes losing rhythmic expression, and their expression continues to exhibit normal oscillations in arrhythmically fed mice. Manipulation of rhythmic food intake also alters the timing of key signaling and metabolic pathways without altering the hepatic clock oscillations. Our findings thus demonstrate that systemic signals driven by rhythmic food intake significantly contribute to driving rhythms in liver gene expression and metabolic functions independently of the cell-autonomous hepatic clock.
每种哺乳动物组织都表现出基因表达的日常节律，以控制组织特异性过程在一天中最合适的时间激活。人们认为，这种节律性表达很大程度上是由体内存在的分子生物钟自主驱动的。通过操纵小鼠的每日摄食节律，我们在这里表明，超过 70%的循环小鼠肝脏转录组在非节律性喂养下失去节律性。值得注意的是，核心时钟基因不属于失去节律性表达的 70%基因之列，它们的表达在非节律性喂养的小鼠中仍继续表现出正常的振荡。节律性食物摄入的操纵也改变了关键信号转导和代谢途径的时间，而不改变肝时钟振荡。因此，我们的研究结果表明，由节律性食物摄入驱动的系统信号显著有助于独立于自主的肝时钟驱动肝脏基因表达和代谢功能的节律。
