Klf15 orchestrates circadian nitrogen homeostasis

Cell Metab. 2012 Mar 7;15(3):311-23. doi: 10.1016/j.cmet.2012.01.020.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Blotting, Western
  • Cell Line
  • Chromatin Immunoprecipitation
  • Circadian Clocks / genetics
  • Circadian Clocks / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Homeostasis / genetics
  • Homeostasis / physiology
  • Humans
  • Kruppel-Like Transcription Factors
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitrogen / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Young Adult

Substances

  • DNA-Binding Proteins
  • Klf15 protein, mouse
  • Kruppel-Like Transcription Factors
  • Transcription Factors
  • Nitrogen

Grant support