Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism

Saikumari Y. Krishnaiah, Gang Wu, Brian J. Altman, Jacqueline Growe, Seth D. Rhoades, Faith Coldren, Anand Venkataraman, Anthony O. Olarerin-George, Lauren J. Francey, Sarmistha Mukherjee, Saiveda Girish, Christopher P. Selby, Sibel Cal, Ubeydullah ER, Bahareh Sianati, Arjun Sengupta, Ron C. Anafi, I. Halil Kavakli, Aziz Sancar, Joseph A. Baur & 3 others Chi V. Dang, John B. Hogenesch, Aalim M. Weljie

Research output: Research - peer-reviewArticle

  • 3 Citations

Abstract

The intricate connection between the circadian clock and metabolism remains poorly understood. We used high temporal resolution metabolite profiling to explore clock regulation of mouse liver and cell-autonomous metabolism. In liver, ∼50% of metabolites were circadian, with enrichment of nucleotide, amino acid, and methylation pathways. In U2 OS cells, 28% were circadian, including amino acids and NAD biosynthesis metabolites. Eighteen metabolites oscillated in both systems and a subset of these in primary hepatocytes. These 18 metabolites were enriched in methylation and amino acid pathways. To assess clock dependence of these rhythms, we used genetic perturbation. BMAL1 knockdown diminished metabolite rhythms, while CRY1 or CRY2 perturbation generally shortened or lengthened rhythms, respectively. Surprisingly, CRY1 knockdown induced 8 hr rhythms in amino acid, methylation, and vitamin metabolites, decoupling metabolite from transcriptional rhythms, with potential impact on nutrient sensing in vivo. These results provide the first comprehensive views of circadian liver and cell-autonomous metabolism.

LanguageEnglish (US)
Pages961-974.e4
JournalCell Metabolism
Volume25
Issue number4
DOIs
StatePublished - Apr 4 2017

Fingerprint

Amino Acids
Methylation
Liver
Circadian Clocks
Vitamins
NAD
Hepatocytes
Nucleotides
Food

Keywords

  • chronometabolism
  • chronopharmacology
  • circadian clock
  • circadian metabolism
  • LCMS
  • mass spectrometry
  • metabolomics
  • translational transcription feedback loop

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Krishnaiah, S. Y., Wu, G., Altman, B. J., Growe, J., Rhoades, S. D., Coldren, F., ... Weljie, A. M. (2017). Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism. Cell Metabolism, 25(4), 961-974.e4. DOI: 10.1016/j.cmet.2017.03.019

Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism. / Krishnaiah, Saikumari Y.; Wu, Gang; Altman, Brian J.; Growe, Jacqueline; Rhoades, Seth D.; Coldren, Faith; Venkataraman, Anand; Olarerin-George, Anthony O.; Francey, Lauren J.; Mukherjee, Sarmistha; Girish, Saiveda; Selby, Christopher P.; Cal, Sibel; ER, Ubeydullah; Sianati, Bahareh; Sengupta, Arjun; Anafi, Ron C.; Kavakli, I. Halil; Sancar, Aziz; Baur, Joseph A.; Dang, Chi V.; Hogenesch, John B.; Weljie, Aalim M.

In: Cell Metabolism, Vol. 25, No. 4, 04.04.2017, p. 961-974.e4.

Research output: Research - peer-reviewArticle

Krishnaiah, SY, Wu, G, Altman, BJ, Growe, J, Rhoades, SD, Coldren, F, Venkataraman, A, Olarerin-George, AO, Francey, LJ, Mukherjee, S, Girish, S, Selby, CP, Cal, S, ER, U, Sianati, B, Sengupta, A, Anafi, RC, Kavakli, IH, Sancar, A, Baur, JA, Dang, CV, Hogenesch, JB & Weljie, AM 2017, 'Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism' Cell Metabolism, vol 25, no. 4, pp. 961-974.e4. DOI: 10.1016/j.cmet.2017.03.019
Krishnaiah SY, Wu G, Altman BJ, Growe J, Rhoades SD, Coldren F et al. Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism. Cell Metabolism. 2017 Apr 4;25(4):961-974.e4. Available from, DOI: 10.1016/j.cmet.2017.03.019
Krishnaiah, Saikumari Y. ; Wu, Gang ; Altman, Brian J. ; Growe, Jacqueline ; Rhoades, Seth D. ; Coldren, Faith ; Venkataraman, Anand ; Olarerin-George, Anthony O. ; Francey, Lauren J. ; Mukherjee, Sarmistha ; Girish, Saiveda ; Selby, Christopher P. ; Cal, Sibel ; ER, Ubeydullah ; Sianati, Bahareh ; Sengupta, Arjun ; Anafi, Ron C. ; Kavakli, I. Halil ; Sancar, Aziz ; Baur, Joseph A. ; Dang, Chi V. ; Hogenesch, John B. ; Weljie, Aalim M./ Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism. In: Cell Metabolism. 2017 ; Vol. 25, No. 4. pp. 961-974.e4
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