Klf15 orchestrates circadian nitrogen homeostasis

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

doi:10.1016/j.cmet.2012.01.020

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Klf15 orchestrates circadian nitrogen homeostasis

Jeyaraj, Darwin Case Cardiovascular Research Institute Harrington Heart and Vascular Institute Department of Medicine Western Reserve University Cleveland, USA - Heart and Vascular Research Center MetroHealth Campus Case Western Reserve University Cleveland, USA
Scheer, Frank A. J. L. Division of Sleep Medicine Brigham and Women s Hospital and Harvard Medical School Boston, USA
Ripperger, Jürgen A. Department of Biology, Division of Biochemistry University of Fribourg, Switzerland
Haldar, Saptarsi M Case Cardiovascular Research Institute Harrington Heart and Vascular Institute Department of Medicine Western Reserve University Cleveland, USA
Lu, Yuan Case Cardiovascular Research Institute Harrington Heart and Vascular Institute Department of Medicine Western Reserve University Cleveland, USA
Prosdocimo, Domenick A. Case Cardiovascular Research Institute Harrington Heart and Vascular Institute Department of Medicine Western Reserve University Cleveland, USA
Eapen, Sam J. Case Cardiovascular Research Institute Harrington Heart and Vascular Institute Department of Medicine Western Reserve University Cleveland, USA
Eapen, Betty L. Case Cardiovascular Research Institute Harrington Heart and Vascular Institute Department of Medicine Western Reserve University Cleveland, USA
Cui, Yingjie Case Cardiovascular Research Institute Harrington Heart and Vascular Institute Department of Medicine Western Reserve University Cleveland, USA
Mahabeleshwar, Ganapathi H. Case Cardiovascular Research Institute Harrington Heart and Vascular Institute Department of Medicine Western Reserve University Cleveland, USA
Lee, Hyoung gon Department of Pathology Western Reserve University Cleveland, USA
Smith, Mark A. Department of Pathology Western Reserve University Cleveland, USA
Casadesus, Gemma Department of Neurosciences Western Reserve University Cleveland, USA
Mintz, Eric M. Department of Biological Sciences Kent State University Kent, USA
Sun, Haipeng Department of Anesthesia UCLA Los Angeles, USA
Wang, Yibin Department of Anesthesia UCLA Los Angeles, USA
Ramsey, Kathryn M. Department of Medicine Northwestern University Feinberg School of Medicine Chicago, USA
Bass, Joseph Department of Medicine Northwestern University Feinberg School of Medicine Chicago, USA
Shea, Steven A. Division of Sleep Medicine Brigham and Women s Hospital and Harvard Medical School Boston, USA
Albrecht, Urs Department of Biology, Division of Biochemistry University of Fribourg, Switzerland
Jain, Mukesh K. Case Cardiovascular Research Institute Harrington Heart and Vascular Institute Department of Medicine Western Reserve University Cleveland, USA

06.03.2012

Published in:

Cell Metabolism. - 2012, vol. 15, no. 3, p. 311–323

English 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.

Faculty

Faculté des sciences et de médecine

Department

Département de Biologie

Language