Klf15 orchestrates circadian nitrogen homeostasis.

Klf15 orchestrates circadian nitrogen homeostasis.
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DOI:
10.1016/j.cmet.2012.01.020
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发表时间:
2012-03-07
期刊:
影响因子:
29
通讯作者:
Jain MK
Jain MK
中科院分区:
生物学1区
文献类型:
--
作者:
Jeyaraj D;Scheer FA;Ripperger JA;Haldar SM;Lu Y;Prosdocimo DA;Eapen SJ;Eapen BL;Cui Y;Mahabeleshwar GH;Lee HG;Smith MA;Casadesus G;Mintz EM;Sun H;Wang Y;Ramsey KM;Bass J;Shea SA;Albrecht U;Jain MK

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氮稳态的日变化是在整个系统发育中观察到的。但这些是否是内源性节律,如果是的话,将氮稳态与生物钟联系起来的分子机制仍然未知。在这里,我们提供的证据表明,一个依赖时钟的外周振荡器,kr<s:1> ppel样因子15转录协调多种酶的节律性表达,这些酶参与哺乳动物氮稳态。特别是,kr<s:1> ppel样因子15缺陷小鼠没有明显的氨基酸节律,氨到尿素解毒的节律性受损。在外部信号中,摄食在调节kr<s:1> ppel样因子15节律和氮稳态中起主导作用。此外,当人类所有的行为、环境和饮食线索都得到控制时,氮稳态仍然表达内源性昼夜节律。因此,在哺乳动物中,氮稳态表现出昼夜节律性,并由kr<s:1> ppel样因子15协调。
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 factor15 transcriptionally coordinates rhythmic expression of multiple enzymes involved in mammalian nitrogen homeostasis. In particular, Krüppel-like factor15-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 factor15 rhythm and nitrogen homeostasis. Further, when all behavioral, environmental and dietary cues were controlled in humans, nitrogen homeostasis still expressed endogenous circadian rhythmicity. Thus, in mammals, nitrogen homeostasis exhibits circadian rhythmicity, and is orchestrated by Krüppel-like factor15.
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