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Science 308 (5724): 1043-1045

Copyright © 2005 by the American Association for the Advancement of Science

Obesity and Metabolic Syndrome in Circadian Clock Mutant Mice

Fred W. Turek,1,3 Corinne Joshu,3,4* Akira Kohsaka,3,4* Emily Lin,3,4* Ganka Ivanova,2,4 Erin McDearmon,3,5 Aaron Laposky,3 Sue Losee-Olson,3 Amy Easton,3 Dalan R. Jensen,6 Robert H. Eckel,6 Joseph S. Takahashi,1,3,5 Joseph Bass2,3,4{dagger}

Abstract: The CLOCK transcription factor is a key component of the molecular circadian clock within pacemaker neurons of the hypothalamic suprachiasmatic nucleus. We found that homozygous Clock mutant mice have a greatly attenuated diurnal feeding rhythm, are hyperphagic and obese, and develop a metabolic syndrome of hyperleptinemia, hyperlipidemia, hepatic steatosis, hyperglycemia, and hypoinsulinemia. Expression of transcripts encoding selected hypothalamic peptides associated with energy balance was attenuated in the Clock mutant mice. These results suggest that the circadian clock gene network plays an important role in mammalian energy balance.

1 Department of Neurology, Northwestern University, Evanston, IL 60208, USA.
2 Department of Medicine, Feinberg School of Medicine, Northwestern University, Evanston, IL 60208, USA.
3 Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA.
4 Evanston Northwestern Healthcare (ENH) Research Institute, Evanston, IL 60208, USA.
5 Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
6 Department of Medicine, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA.

Published online 21 April 2005

Include this information when citing this paper.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: j-bass{at}

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M. Akashi, H. Soma, T. Yamamoto, A. Tsugitomi, S. Yamashita, T. Yamamoto, E. Nishida, A. Yasuda, J. K. Liao, and K. Node (2010)
PNAS 107, 15643-15648
   Abstract »    Full Text »    PDF »
Nuclear Receptors Linking Circadian Rhythms and Cardiometabolic Control.
H. Duez and B. Staels (2010)
Arterioscler Thromb Vasc Biol 30, 1529-1534
   Abstract »    Full Text »    PDF »
Correct biological timing in Arabidopsis requires multiple light-signaling pathways.
N. Dalchau, K. E. Hubbard, F. C. Robertson, C. T. Hotta, H. M. Briggs, G.-B. Stan, J. M. Goncalves, and A. A. R. Webb (2010)
PNAS 107, 13171-13176
   Abstract »    Full Text »    PDF »
CLOCK Regulates Circadian Rhythms of Hepatic Glycogen Synthesis through Transcriptional Activation of Gys2.
R. Doi, K. Oishi, and N. Ishida (2010)
J. Biol. Chem. 285, 22114-22121
   Abstract »    Full Text »    PDF »
No time to lose: workshop on circadian rhythms and metabolic disease.
C. M. Silva, S. Sato, and R. N. Margolis (2010)
Genes & Dev. 24, 1456-1464
   Abstract »    Full Text »    PDF »
Kruppel-Like Factor KLF10 Is a Link between the Circadian Clock and Metabolism in Liver.
F. Guillaumond, A. Grechez-Cassiau, M. Subramaniam, S. Brangolo, B. Peteri-Brunback, B. Staels, C. Fievet, T. C. Spelsberg, F. Delaunay, and M. Teboul (2010)
Mol. Cell. Biol. 30, 3059-3070
   Abstract »    Full Text »    PDF »
A circadian-regulated gene, Nocturnin, promotes adipogenesis by stimulating PPAR-{gamma} nuclear translocation.
M. Kawai, C. B. Green, B. Lecka-Czernik, N. Douris, M. R. Gilbert, S. Kojima, C. Ackert-Bicknell, N. Garg, M. C. Horowitz, M. L. Adamo, et al. (2010)
PNAS 107, 10508-10513
   Abstract »    Full Text »    PDF »
Treatment of obesity with extension of sleep duration: a randomized, prospective, controlled trial.
G. Cizza, P. Marincola, M. Mattingly, L. Williams, M. Mitler, M. Skarulis, and G. Csako (2010)
Clinical Trials 7, 274-285
   Abstract »    PDF »

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