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Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression

  1. Christopher Vollmersa,b,
  2. Shubhroz Gilla,c,
  3. Luciano DiTacchioa,
  4. Sandhya R. Pulivarthya,
  5. Hiep D. Lea and
  6. Satchidananda Pandaa,1
  1. aRegulatory Biology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037;
  2. bHeidelberg University Biochemistry Center (BZH), 69120 Heidelberg, Germany; and
  3. cDivision of Biological Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093

  1. Edited by Ronald M. Evans, The Salk Institute for Biological Studies, La Jolla, CA, and approved October 13, 2009 (received for review August 24, 2009)

Abstract

In mammals, the circadian oscillator generates approximately 24-h rhythms in feeding behavior, even under constant environmental conditions. Livers of mice held under constant darkness exhibit circadian rhythm in abundance in up to 15% of expressed transcripts. Therefore, oscillations in hepatic transcripts could be driven by rhythmic food intake or sustained by the hepatic circadian oscillator, or a combination of both. To address this question, we used distinct feeding and fasting paradigms on wild-type (WT) and circadian clock-deficient mice. We monitored temporal patterns of feeding and hepatic transcription. Both food availability and the temporal pattern of feeding determined the repertoire, phase, and amplitude of the circadian transcriptome in WT liver. In the absence of feeding, only a small subset of transcripts continued to express circadian patterns. Conversely, temporally restricted feeding restored rhythmic transcription of hundreds of genes in oscillator-deficient mouse liver. Our findings show that both temporal pattern of food intake and the circadian clock drive rhythmic transcription, thereby highlighting temporal regulation of hepatic transcription as an emergent property of the circadian system.

Footnotes

  • 1To whom correspondence should be addressed. E-mail: panda{at}salk.edu

  • Author contributions: C.V., L.D., and S.P. designed research; C.V., S.R.P., and H.D.L. performed research; C.V., S.G., and S.P. analyzed data; and C.V. and S.P. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE13093).

  • This article contains supporting information online at www.pnas.org/cgi/content/full/0909591106/DCSupplemental.

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