Case Cardiovascular Research Institute, Harrington Heart and Vascular Institute, Department of Medicine, Western Reserve University, Cleveland, OH 44106, USA.
Cell Metab. 2012 Mar 7;15(3):311-23. doi: 10.1016/j.cmet.2012.01.020.
Diurnal variation in nitrogen homeostasis is observed across phylogeny. But whether these are endogenous rhythms, and if so, molecular mechanisms that link nitrogen homeostasis to the circadian clock remain unknown. Here, we provide evidence that a clock-dependent peripheral oscillator, Krüppel-like factor 15 transcriptionally coordinates rhythmic expression of multiple enzymes involved in mammalian nitrogen homeostasis. In particular, Krüppel-like factor 15-deficient mice exhibit no discernable amino acid rhythm, and the rhythmicity of ammonia to urea detoxification is impaired. Of the external cues, feeding plays a dominant role in modulating Krüppel-like factor 15 rhythm and nitrogen homeostasis. Further, when all behavioral, environmental and dietary cues were controlled in humans, nitrogen homeostasis exhibited an endogenous circadian rhythmicity. Thus, in mammals, nitrogen homeostasis exhibits circadian rhythmicity, and is orchestrated by Krüppel-like factor 15.
氮动态平衡在生物进化中表现出昼夜节律变化。但是，这些变化是否是内源性节律，以及将氮动态平衡与生物钟联系起来的分子机制尚不清楚。本文提供了证据表明，一种依赖于时钟的外周振荡器，即 Krüppel 样因子 15，转录协调参与哺乳动物氮动态平衡的多种酶的节律性表达。具体而言，Krüppel 样因子 15 缺陷型小鼠没有明显的氨基酸节律，氨到尿素解毒的节律性受损。在外部线索中，进食在调节 Krüppel 样因子 15 节律和氮动态平衡方面起着主导作用。此外，当人类控制所有行为、环境和饮食线索时，氮动态平衡表现出内源性的昼夜节律性。因此，在哺乳动物中，氮动态平衡表现出昼夜节律性，并且由 Krüppel 样因子 15 协调。
