METABOLISM A Cellular Fuel Sensor

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]

The editors suggest the following Related Resources on Science sites:

In Science Signaling

EDITORIAL GUIDES
Focus Issue: Diabetes—Fighting Fat on Multiple Fronts

Elizabeth M. Adler (25 January 2005)
Sci. STKE 2005 (268), eg2. [DOI: 10.1126/stke.2682005eg2]
 |  Abstract »  |  Full Text »  |  PDF »

REVIEWS
TOR Signaling

Thurl E. Harris and John C. Lawrence, Jr. (9 December 2003)
Sci. STKE 2003 (212), re15. [DOI: 10.1126/stke.2122003re15]
 |  Gloss »  |  Abstract »  |  Full Text »  |  PDF »