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.
UR - http://www.scopus.com/inward/record.url?scp=84863230321&partnerID=8YFLogxK
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U2 - 10.1016/j.cmet.2012.01.020
DO - 10.1016/j.cmet.2012.01.020
M3 - Article
C2 - 22405069
AN - SCOPUS:84863230321
SN - 1550-4131
VL - 15
SP - 311
EP - 323
JO - Cell Metabolism
JF - Cell Metabolism
IS - 3
ER -