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Originally published in Science Express on 21 April 2005
Science 13 May 2005:
Vol. 308. no. 5724, pp. 1043 - 1045
DOI: 10.1126/science.1108750
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Reports

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}

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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