title: Klf15 orchestrates circadian nitrogen homeostasis.
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.
authors.affiliation: Case Cardiovascular Research Institute, Harrington Heart and Vascular Institute, Department of Medicine, Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Darwin
authors.initials: D
authors.lastname: Jeyaraj
authors.forename: Frank A J L
authors.initials: FA
authors.lastname: Scheer
authors.forename: Jürgen A
authors.initials: JA
authors.lastname: Ripperger
authors.forename: Saptarsi M
authors.initials: SM
authors.lastname: Haldar
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.forename: Domenick A
authors.initials: DA
authors.lastname: Prosdocimo
authors.forename: Sam J
authors.initials: SJ
authors.lastname: Eapen
authors.forename: Betty L
authors.initials: BL
authors.lastname: Eapen
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Cui
authors.forename: Ganapathi H
authors.initials: GH
authors.lastname: Mahabeleshwar
authors.forename: Hyoung-gon
authors.initials: HG
authors.lastname: Lee
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: Gemma
authors.initials: G
authors.lastname: Casadesus
authors.forename: Eric M
authors.initials: EM
authors.lastname: Mintz
authors.forename: Haipeng
authors.initials: H
authors.lastname: Sun
authors.forename: Yibin
authors.initials: Y
authors.lastname: Wang
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Ramsey
authors.forename: Joseph
authors.initials: J
authors.lastname: Bass
authors.forename: Steven A
authors.initials: SA
authors.lastname: Shea
authors.forename: Urs
authors.initials: U
authors.lastname: Albrecht
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Jain
mesh_terms: D000328:Adult; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D057906:Circadian Clocks / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009584:Nitrogen / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C467418:Klf15 protein, mouse; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; D009584:Nitrogen