Editors' ChoiceMetabolism

A Cellular Fuel Sensor

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Science's STKE  16 May 2006:
Vol. 2006, Issue 335, pp. tw163
DOI: 10.1126/stke.3352006tw163

The brain plays a key role in body weight control. Within the hypothalamus, select populations of neurons sense changes in fuel availability and regulate food intake and metabolism, but the underlying signaling mechanisms have not been well understood. Cota et al. (see the Perspective by Flier) implicate the atypical kinase mTOR (mammalian target of rapamycin) signaling pathway, which has been widely studied in other cell types, where it regulates the rate of protein synthesis. In rodents, central administration of leucine, which increases mTOR signaling in nonneuronal cells, activated hypothalamic mTOR signaling and decreased food intake and body weight.

D. Cota, K. Proulx, K. A. Blake Smith, S. C. Kozma, G. Thomas, S. C. Woods, R. J. Seeley, Hypothalamic mTOR signaling regulates food intake. Science 312, 927-930 (2006). [Abstract] [Full Text]

J. S. Flier, Regulating energy balance: The substrate strikes back. Science 312, 861-864 (2006). [Summary] [Full Text]

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