Klf15 orchestrates circadian nitrogen homeostasis

Darwin Jeyaraj, Frank A.J.L. Scheer, Jürgen A. Ripperger, Saptarsi M. Haldar, Yuan Lu, Domenick A. Prosdocimo, Sam J. Eapen, Betty L. Eapen, Yingjie Cui, Ganapathi H. Mahabeleshwar, Hyoung Gon Lee, Mark A. Smith, Gemma Casadesus, Eric M. Mintz, Haipeng Sun, Yibin Wang, Kathryn M. Ramsey, Joseph Bass, Steven A. Shea, Urs AlbrechtMukesh K. Jain

Research output: Contribution to journalArticlepeer-review

104 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)311-323
Number of pages13
JournalCell Metabolism
Issue number3
StatePublished - Mar 7 2012
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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