Klf15 orchestrates circadian nitrogen homeostasis.

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
Cell Metab. 2012 15 (3): 311-23

PMID: 22405069 · PMCID: PMC3299986 · 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.

Copyright © 2012 Elsevier Inc. All rights reserved.

MeSH Terms (17)

Adult Animals Blotting, Western Cell Line Chromatin Immunoprecipitation Circadian Clocks DNA-Binding Proteins Homeostasis Humans Male Mice Mice, Inbred C57BL Mice, Knockout Nitrogen Real-Time Polymerase Chain Reaction Transcription Factors Young Adult

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