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Klf15 orchestrates circadian nitrogen homeostasis
Darwin Jeyaraj1, Frank A J L Scheer, Jürgen A Ripperger
1Case Cardiovascular Research Institute, Harrington Heart and Vascular Institute, Department of Medicine, Western Reserve University, Cleveland, OH 44106, USA.
Mammalian nitrogen homeostasis follows a daily rhythm, orchestrated by the Krüppel-like factor 15 (KLF15) protein. This internal clock mechanism regulates key enzymes, even under controlled conditions.
Area of Science:
- Biochemistry
- Chronobiology
- Physiology
Background:
- Diurnal variations in nitrogen homeostasis are known across species.
- The endogenous nature and molecular links between nitrogen homeostasis and circadian rhythms are poorly understood.
Purpose of the Study:
- To investigate the endogenous circadian regulation of mammalian nitrogen homeostasis.
- To identify molecular mechanisms linking nitrogen homeostasis to the circadian clock.
Main Methods:
- Utilized Krüppel-like factor 15-deficient mice models.
- Monitored amino acid rhythms and ammonia to urea detoxification.
- Controlled environmental, behavioral, and dietary cues in human studies.
Main Results:
- Krüppel-like factor 15 (KLF15) transcriptionally coordinates rhythmic expression of enzymes in nitrogen metabolism.
- KLF15-deficient mice lack amino acid rhythms and show impaired urea detoxification rhythms.
- Nitrogen homeostasis exhibits endogenous circadian rhythmicity in humans, independent of external cues.
Conclusions:
- Mammalian nitrogen homeostasis is under circadian control.
- Krüppel-like factor 15 is a key molecular link between the circadian clock and nitrogen homeostasis.
- Feeding is a significant modulator of KLF15 rhythm and nitrogen metabolism.
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