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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}northwestern.edu

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E. Maury, K. M. Ramsey, and J. Bass (2010)
Circ. Res. 106, 447-462
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Metabolism and Circadian Rhythms--Implications for Obesity.
O. Froy (2010)
Endocr. Rev. 31, 1-24
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Rhythmic changes in colonic motility are regulated by period genes.
W. A. Hoogerwerf, V. B. Shahinian, G. Cornelissen, F. Halberg, J. Bostwick, J. Timm, P. A. Bartell, and V. M. Cassone (2010)
Am J Physiol Gastrointest Liver Physiol 298, G143-G150
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Direct Regulation of Myocardial Triglyceride Metabolism by the Cardiomyocyte Circadian Clock.
J.-Y. Tsai, P. C. Kienesberger, T. Pulinilkunnil, M. H. Sailors, D. J. Durgan, C. Villegas-Montoya, A. Jahoor, R. Gonzalez, M. E. Garvey, B. Boland, et al. (2010)
J. Biol. Chem. 285, 2918-2929
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Circadian Expression of Adiponectin and Its Receptors in Human Adipose Tissue.
P. Gomez-Abellan, C. Gomez-Santos, J. A. Madrid, F. I. Milagro, J. Campion, J. A. Martinez, J. M. Ordovas, and M. Garaulet (2010)
Endocrinology 151, 115-122
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Influence of Age on Clock Gene Expression in Peripheral Blood Cells of Healthy Women.
H. Ando, K. Ushijima, M. Kumazaki, T. Takamura, N. Yokota, T. Saito, S. Irie, S. Kaneko, and A. Fujimura (2010)
J Gerontol A Biol Sci Med Sci 65A, 9-13
   Abstract »    Full Text »    PDF »
Shift work: coping with the biological clock.
J. Arendt (2010)
Occup. Med. 60, 10-20
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Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
C. Vollmers, S. Gill, L. DiTacchio, S. R. Pulivarthy, H. D. Le, and S. Panda (2009)
PNAS 106, 21453-21458
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Light-Mediated Perturbations of Circadian Timing and Cancer Risk: A Mechanistic Analysis.
R. J. Reiter, Dan Xian Tan, T. C. Erren, L. Fuentes-Broto, and S. D. Paredes (2009)
Integr Cancer Ther 8, 354-360
   Abstract »    PDF »
Rev-erb-{alpha}: an integrator of circadian rhythms and metabolism.
H. Duez and B. Staels (2009)
J Appl Physiol 107, 1972-1980
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