Klf15 orchestrates circadian nitrogen homeostasis

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

doi:10.1016/j.cmet.2012.01.020

Klf15 orchestrates circadian nitrogen homeostasis

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

^*Corresponding author for this work

Medicine, Endocrinology Division

Research output: Contribution to journal › Article › peer-review

113 Scopus citations

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.

Original language	English (US)
Pages (from-to)	311-323
Number of pages	13
Journal	Cell Metabolism
Volume	15
Issue number	3
DOIs	https://doi.org/10.1016/j.cmet.2012.01.020
State	Published - Mar 7 2012

Funding

We are grateful to Drs. Alfred F. Connors, Jr., David S. Rosenbaum, Jonathan S. Stamler, Douglas T. Hess, and Satish C. Kalhan for support and suggestions, to Dr. Ueli Schibler for reagents, to Drs. John Le Lay and Klaus H. Kaestner for providing chromatin immunoprecipitation protocol, to Ken Grimes and Wanda Snead at the Vanderbilt MMPC, to Dana Lee at the Cincinnati MMPC, to Jenny Marks at BWH, to Diana Awad Scrocco for proofreading, to Mike Mustar for artistic illustrations, to the CWRU Rodent Behavior Core, and to members of the Jain laboratory for their assistance. Funding sources: NIH grants HL094660 (D.J.), R01-HL09480601 and P30-HL101299 (F.A.J.L.S.); K24-HL76446 (S.A.S.); HL072952 (S.M.H.); HL097023 (G.H.M.); HL075427, HL076754, HL084154, HL086548, and HL097595 (M.K.J.); DK059630 (Cincinnati MMPC); DK59637 (Vanderbilt MMPC); SNF grant 31003A/131086 (U.A.); and M01-RR02635 (BWH).

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2012.01.020

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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., ... Jain, M. K. (2012). Klf15 orchestrates circadian nitrogen homeostasis. Cell Metabolism, 15(3), 311-323. https://doi.org/10.1016/j.cmet.2012.01.020

@article{ced0edb30f8c4fe292f8f23dab41bd09,

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, Kr{\"u}ppel-like factor 15 transcriptionally coordinates rhythmic expression of multiple enzymes involved in mammalian nitrogen homeostasis. In particular, Kr{\"u}ppel-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 Kr{\"u}ppel-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 Kr{\"u}ppel-like factor 15.",

author = "Darwin Jeyaraj and Scheer, {Frank A.J.L.} and Ripperger, {J{\"u}rgen A.} and Haldar, {Saptarsi M.} and Yuan Lu and Prosdocimo, {Domenick A.} and Eapen, {Sam J.} and Eapen, {Betty L.} and Yingjie Cui and Mahabeleshwar, {Ganapathi H.} and Lee, {Hyoung Gon} and Smith, {Mark A.} and Gemma Casadesus and Mintz, {Eric M.} and Haipeng Sun and Yibin Wang and Ramsey, {Kathryn M.} and Joseph Bass and Shea, {Steven A.} and Urs Albrecht and Jain, {Mukesh K.}",

note = "Funding Information: We are grateful to Drs. Alfred F. Connors, Jr., David S. Rosenbaum, Jonathan S. Stamler, Douglas T. Hess, and Satish C. Kalhan for support and suggestions, to Dr. Ueli Schibler for reagents, to Drs. John Le Lay and Klaus H. Kaestner for providing chromatin immunoprecipitation protocol, to Ken Grimes and Wanda Snead at the Vanderbilt MMPC, to Dana Lee at the Cincinnati MMPC, to Jenny Marks at BWH, to Diana Awad Scrocco for proofreading, to Mike Mustar for artistic illustrations, to the CWRU Rodent Behavior Core, and to members of the Jain laboratory for their assistance. Funding sources: NIH grants HL094660 (D.J.), R01-HL09480601 and P30-HL101299 (F.A.J.L.S.); K24-HL76446 (S.A.S.); HL072952 (S.M.H.); HL097023 (G.H.M.); HL075427, HL076754, HL084154, HL086548, and HL097595 (M.K.J.); DK059630 (Cincinnati MMPC); DK59637 (Vanderbilt MMPC); SNF grant 31003A/131086 (U.A.); and M01-RR02635 (BWH). ",

year = "2012",

month = mar,

day = "7",

doi = "10.1016/j.cmet.2012.01.020",

language = "English (US)",

volume = "15",

pages = "311--323",

journal = "Cell Metabolism",

issn = "1550-4131",

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Jeyaraj, D, Scheer, FAJL, Ripperger, JA, Haldar, SM, Lu, Y, Prosdocimo, DA, Eapen, SJ, Eapen, BL, Cui, Y, Mahabeleshwar, GH, Lee, HG, Smith, MA, Casadesus, G, Mintz, EM, Sun, H, Wang, Y, Ramsey, KM , Bass, J, Shea, SA, Albrecht, U & Jain, MK 2012, 'Klf15 orchestrates circadian nitrogen homeostasis', Cell Metabolism, vol. 15, no. 3, pp. 311-323. https://doi.org/10.1016/j.cmet.2012.01.020

TY - JOUR

T1 - Klf15 orchestrates circadian nitrogen homeostasis

AU - Jeyaraj, Darwin

AU - Scheer, Frank A.J.L.

AU - Ripperger, Jürgen A.

AU - Haldar, Saptarsi M.

AU - Lu, Yuan

AU - Prosdocimo, Domenick A.

AU - Eapen, Sam J.

AU - Eapen, Betty L.

AU - Cui, Yingjie

AU - Mahabeleshwar, Ganapathi H.

AU - Lee, Hyoung Gon

AU - Smith, Mark A.

AU - Casadesus, Gemma

AU - Mintz, Eric M.

AU - Sun, Haipeng

AU - Wang, Yibin

AU - Ramsey, Kathryn M.

AU - Bass, Joseph

AU - Shea, Steven A.

AU - Albrecht, Urs

AU - Jain, Mukesh K.

N1 - Funding Information: We are grateful to Drs. Alfred F. Connors, Jr., David S. Rosenbaum, Jonathan S. Stamler, Douglas T. Hess, and Satish C. Kalhan for support and suggestions, to Dr. Ueli Schibler for reagents, to Drs. John Le Lay and Klaus H. Kaestner for providing chromatin immunoprecipitation protocol, to Ken Grimes and Wanda Snead at the Vanderbilt MMPC, to Dana Lee at the Cincinnati MMPC, to Jenny Marks at BWH, to Diana Awad Scrocco for proofreading, to Mike Mustar for artistic illustrations, to the CWRU Rodent Behavior Core, and to members of the Jain laboratory for their assistance. Funding sources: NIH grants HL094660 (D.J.), R01-HL09480601 and P30-HL101299 (F.A.J.L.S.); K24-HL76446 (S.A.S.); HL072952 (S.M.H.); HL097023 (G.H.M.); HL075427, HL076754, HL084154, HL086548, and HL097595 (M.K.J.); DK059630 (Cincinnati MMPC); DK59637 (Vanderbilt MMPC); SNF grant 31003A/131086 (U.A.); and M01-RR02635 (BWH).

PY - 2012/3/7

Y1 - 2012/3/7

N2 - 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.

AB - 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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U2 - 10.1016/j.cmet.2012.01.020

DO - 10.1016/j.cmet.2012.01.020

M3 - Article

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AN - SCOPUS:84863230321

SN - 1550-4131

VL - 15

SP - 311

EP - 323

JO - Cell Metabolism

JF - Cell Metabolism

IS - 3

ER -

Klf15 orchestrates circadian nitrogen homeostasis

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