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Science 312 (5775): 927-930

Copyright © 2006 by the American Association for the Advancement of Science

Hypothalamic mTOR Signaling Regulates Food Intake

Daniela Cota,1 Karine Proulx,1 Kathi A. Blake Smith,1 Sara C. Kozma,2 George Thomas,2 Stephen C. Woods,1 Randy J. Seeley1*

Abstract: The mammalian Target of Rapamycin (mTOR) protein is a serine-threonine kinase that regulates cell-cycle progression and growth by sensing changes in energy status. We demonstrated that mTOR signaling plays a role in the brain mechanisms that respond to nutrient availability, regulating energy balance. In the rat, mTOR signaling is controlled by energy status in specific regions of the hypothalamus and colocalizes with neuropeptide Y and proopiomelanocortin neurons in the arcuate nucleus. Central administration of leucine increases hypothalamic mTOR signaling and decreases food intake and body weight. The hormone leptin increases hypothalamic mTOR activity, and the inhibition of mTOR signaling blunts leptin's anorectic effect. Thus, mTOR is a cellular fuel sensor whose hypothalamic activity is directly tied to the regulation of energy intake.

1 Department of Psychiatry, University of Cincinnati, Genome Research Institute, 2170 East Galbraith Road, Cincinnati, OH 45237, USA.
2 Department of Genome Science, University of Cincinnati, Genome Research Institute, 2170 East Galbraith Road, Cincinnati, OH 45237, USA.

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

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A Mouse Model of Tuberous Sclerosis: Neuronal Loss of Tsc1 Causes Dysplastic and Ectopic Neurons, Reduced Myelination, Seizure Activity, and Limited Survival.
L. Meikle, D. M. Talos, H. Onda, K. Pollizzi, A. Rotenberg, M. Sahin, F. E. Jensen, and D. J. Kwiatkowski (2007)
J. Neurosci. 27, 5546-5558
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Amino acids, taste circuits, and feeding behavior in Drosophila: towards understanding the psychology of feeding in flies and man.
C. Melcher, R. Bader, and M. J Pankratz (2007)
J. Endocrinol. 192, 467-472
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Appropriate Inhibition of Orexigenic Hypothalamic Arcuate Nucleus Neurons Independently of Leptin Receptor/STAT3 Signaling.
H. Munzberg, E. E. Jobst, S. H. Bates, J. Jones, E. Villanueva, R. Leshan, M. Bjornholm, J. Elmquist, M. Sleeman, M. A. Cowley, et al. (2007)
J. Neurosci. 27, 69-74
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AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues.
B. Xue and B. B. Kahn (2006)
J. Physiol. 574, 73-83
   Abstract »    Full Text »    PDF »
Neuroscience. Regulating energy balance: the substrate strikes back..
J. S. Flier (2006)
Science 312, 861-864
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