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Science 19 January 2001:
Vol. 291. no. 5503, pp. 490 - 493
DOI: 10.1126/science.291.5503.490
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Reports

Entrainment of the Circadian Clock in the Liver by Feeding

Karl-Arne Stokkan,12* Shin Yamazaki,1* Hajime Tei,3 Yoshiyuki Sakaki,3 Michael Menaker1dagger

Circadian rhythms of behavior are driven by oscillators in the brain that are coupled to the environmental light cycle. Circadian rhythms of gene expression occur widely in peripheral organs. It is unclear how these multiple rhythms are coupled together to form a coherent system. To study such coupling, we investigated the effects of cycles of food availability (which exert powerful entraining effects on behavior) on the rhythms of gene expression in the liver, lung, and suprachiasmatic nucleus (SCN). We used a transgenic rat model whose tissues express luciferase in vitro. Although rhythmicity in the SCN remained phase-locked to the light-dark cycle, restricted feeding rapidly entrained the liver, shifting its rhythm by 10 hours within 2 days. Our results demonstrate that feeding cycles can entrain the liver independently of the SCN and the light cycle, and they suggest the need to reexamine the mammalian circadian hierarchy. They also raise the possibility that peripheral circadian oscillators like those in the liver may be coupled to the SCN primarily through rhythmic behavior, such as feeding.

1 National Science Foundation Center for Biological Timing and Department of Biology, University of Virginia, P.O. Box 400328, Charlottesville, VA 22904-4328, USA.
2 Department of Arctic Biology and Institute of Medical Biology, University of Tromsø, N-9037 Tromsø, Norway.
3 Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: mm7e{at}virginia.edu

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Inaugural Article: PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues.
S.-H. Yoo, S. Yamazaki, P. L. Lowrey, K. Shimomura, C. H. Ko, E. D. Buhr, S. M. Siepka, H.-K. Hong, W. J. Oh, O. J. Yoo, et al. (2004)
PNAS 101, 5339-5346
   Abstract »    Full Text »    PDF »
Retinal Circadian Clocks and Control of Retinal Physiology.
C. B. Green and J. C. Besharse (2004)
J Biol Rhythms 19, 91-102
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An ultradian clock shapes genome expression in yeast.
M. W. Young (2004)
PNAS 101, 1118-1119
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A Circadian Rhythm in the Expression of PERIOD2 Protein Reveals a Novel SCN-Controlled Oscillator in the Oval Nucleus of the Bed Nucleus of the Stria Terminalis.
S. Amir, E. W. Lamont, B. Robinson, and J. Stewart (2004)
J. Neurosci. 24, 781-790
   Abstract »    Full Text »    PDF »


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