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Publication
Klf15 orchestrates circadian nitrogen homeostasis.
Authors 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
Submitted By Submitted Externally on 9/18/2012
Status Published
Journal Cell Metabolism
Year 2012
Date Published
Volume : Pages 15 : 311 - 323
PubMed Reference 22405069
Abstract 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.




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