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Science 320 (5879): 1074-1077

Copyright © 2008 by the American Association for the Advancement of Science

Differential Rescue of Light- and Food-Entrainable Circadian Rhythms

Patrick M. Fuller, Jun Lu, Clifford B. Saper*

Abstract: When food is plentiful, circadian rhythms of animals are powerfully entrained by the light-dark cycle. However, if animals have access to food only during their normal sleep cycle, they will shift most of their circadian rhythms to match the food availability. We studied the basis for entrainment of circadian rhythms by food and light in mice with targeted disruption of the clock gene Bmal1, which lack circadian rhythmicity. Injection of a viral vector containing the Bmal1 gene into the suprachiasmatic nuclei of the hypothalamus restored light-entrainable, but not food-entrainable, circadian rhythms. In contrast, restoration of the Bmal1 gene only in the dorsomedial hypothalamic nucleus restored the ability of animals to entrain to food but not to light. These results demonstrate that the dorsomedial hypothalamus contains a Bmal1-based oscillator that can drive food entrainment of circadian rhythms.

Department of Neurology, Division of Sleep Medicine, and Program in Neuroscience, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

* To whom correspondence should be addressed. E-mail: csaper{at}

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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U. Abraham, M. Saleh, and A. Kramer (2013)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    PDF »
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A. Atwood, R. DeConde, S. S. Wang, T. C. Mockler, J. S. M. Sabir, T. Ideker, and S. A. Kay (2011)
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   Abstract »    Full Text »    PDF »
Circadian intervention of obesity development via resting-stage feeding manipulation or oxytocin treatment.
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   Abstract »    Full Text »    PDF »
Bmal1 in the Nervous System Is Essential for Normal Adaptation of Circadian Locomotor Activity and Food Intake to Periodic Feeding.
M. Mieda and T. Sakurai (2011)
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   Abstract »    Full Text »    PDF »
Interaction between hypothalamic dorsomedial nucleus and the suprachiasmatic nucleus determines intensity of food anticipatory behavior.
G. Acosta-Galvan, C.-X. Yi, J. van der Vliet, J. H. Jhamandas, P. Panula, M. Angeles-Castellanos, M. del Carmen Basualdo, C. Escobar, and R. M. Buijs (2011)
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   Abstract »    Full Text »    PDF »
Feeding Time Synchronizes Clock Gene Rhythmic Expression in Brain and Liver of Goldfish (Carassius auratus).
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   Abstract »    PDF »
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K. M. Ramsey and J. Bass (2011)
Cold Spring Harb Symp Quant Biol 76, 63-72
   Abstract »    Full Text »    PDF »
Light at night increases body mass by shifting the time of food intake.
L. K. Fonken, J. L. Workman, J. C. Walton, Z. M. Weil, J. S. Morris, A. Haim, and R. J. Nelson (2010)
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   Abstract »    Full Text »    PDF »
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C. M. Silva, S. Sato, and R. N. Margolis (2010)
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   Abstract »    Full Text »    PDF »
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A. Crocker and A. Sehgal (2010)
Genes & Dev. 24, 1220-1235
   Abstract »    Full Text »    PDF »
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E. Maury, K. M. Ramsey, and J. Bass (2010)
Circ. Res. 106, 447-462
   Abstract »    Full Text »    PDF »
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E. Szentirmai, L. Kapas, Y. Sun, R. G. Smith, and J. M. Krueger (2010)
Am J Physiol Regulatory Integrative Comp Physiol 298, R467-R477
   Abstract »    Full Text »    PDF »
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L. Shi, M. L. Ko, and G. Y.-P. Ko (2009)
J. Biol. Chem. 284, 25791-25803
   Abstract »    Full Text »    PDF »
Clock is important for food and circadian regulation of macronutrient absorption in mice.
X. Pan and M. M. Hussain (2009)
J. Lipid Res. 50, 1800-1813
   Abstract »    Full Text »    PDF »
Stomach ghrelin-secreting cells as food-entrainable circadian clocks.
J. LeSauter, N. Hoque, M. Weintraub, D. W. Pfaff, and R. Silver (2009)
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   Abstract »    Full Text »    PDF »
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N. Tsujino and T. Sakurai (2009)
Pharmacol. Rev. 61, 162-176
   Abstract »    Full Text »    PDF »
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K.-F. Storch and C. J. Weitz (2009)
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   Abstract »    Full Text »    PDF »
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L. Marpegan, T. J. Krall, and E. D. Herzog (2009)
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   Abstract »    PDF »
Diurnal expression of functional and clock-related genes throughout the rat HPA axis: system-wide shifts in response to a restricted feeding schedule.
M. Girotti, M. S. Weinberg, and R. L. Spencer (2009)
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   Abstract »    Full Text »    PDF »
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F. A. J. L. Scheer, M. F. Hilton, C. S. Mantzoros, and S. A. Shea (2009)
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   Abstract »    Full Text »    PDF »
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J. A. Gonzalez, E. Horjales-Araujo, L. Fugger, C. Broberger, and D. Burdakov (2009)
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   Abstract »    Full Text »    PDF »
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   Abstract »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Comment on "Differential Rescue of Light- and Food-Entrainable Circadian Rhythms".
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   Abstract »    Full Text »    PDF »
Response to Comment on "Differential Rescue of Light- and Food-Entrainable Circadian Rhythms".
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Science 322, 675b
   Abstract »    Full Text »    PDF »

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