Klf15 orchestrates circadian nitrogen homeostasis
Open accessAbstract
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.
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Amino acid plasma concentrations are under endogenous circadian control through Krüppel-like factor 15-control of the rhythmic expression of multiple enzymes involved in mammalian nitrogen homeostasis.
“Recent research demonstrates that amino acid plasma concentrations are under endogenous circadian control, through Krüppel-like factor 15-control of the rhythmic expression of multiple enzymes involved in mammalian nitrogen homeostasis (Jeyaraj et al., 2012).”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Jeyaraj et al., 2012
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- Authors
- Jeyaraj, D., Scheer, F. A. J. L., Ripperger, J. A., Haldar, S. M., Lu, Y., Prosdocimo, D. A., Eapen, S. J., Eapen, B. L., Cui, Y., Mahabeleshwar, G. H., Lee, H.-G., Smith, M. A., Casadesus, G., Mintz, E. M., Sun, H., Wang, Y., Ramsey, K. M., Bass, J., Shea, S. A., Albrecht, U., & Jain, M. K.
- Affiliations
- MetroHealth (US)
- Brigham and Women's Hospital (US)
- University of Fribourg (CH)
- Case Western Reserve University (US)
- Kent State University (US)
- University of California, Los Angeles (US)
- Northwestern University (US)
- Corresponding author
- Jain, Mukesh K.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 15
- Issue
- 3
- Pages
- 311-323
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3299986
- OpenAlex
- W2165532538
- Cited by
- 154
- References
- 56
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 20 · 2023: 9 · 2022: 6 · 2021: 19 · 2020: 16 · 2019: 11 · 2018: 11 · 2017: 7 · 2016: 8 · 2015: 9 · 2014: 10 · 2013: 7 · 2012: 5
- FWCI
- 4.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- reroDoc Digital Library (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL 084154, R01HL084154, HL094660, T32HL105338, HL 086548, K24HL076446, HL-076754, R00HL097023, HL075427, R01-HL09480601, R01HL110630, R01HL094806, R01HL075427, K99HL097023, R01HL072952, R01HL086548, HL097595, R01HL097593, R01HL103205, K08HL094660, P30HL101299, R01HL076754, HL097023, HL072952)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK59637, DK059630, U24DK059637, U24DK059630)
- National Center for Research Resources (M01RR002635)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- KLF15, circadian clock, nitrogen homeostasis, ammonia detoxification, urea cycle, peripheral oscillators, feeding cues, endogenous rhythms
- MeSH terms
- Adult, Animals, Cell Line, DNA-Binding Proteins, Homeostasis, Humans, Male, Mice, Inbred C57BL, Nitrogen, Transcription Factors, Blotting, Western, Mice, Knockout, Chromatin Immunoprecipitation, Mice, Kruppel-Like Transcription Factors, Young Adult, Circadian Clocks, Real-Time Polymerase Chain Reaction
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