Healthy Appetite

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Science  04 Jun 2004:
Vol. 304, Issue 5676, pp. 1415
DOI: 10.1126/science.304.5676.1415b

Since its discovery 5 years ago, the stomach-derived peptide ghrelin has been the subject of intense research. Dubbed the “hunger hormone,” ghrelin stimulates food intake and body weight gain when administered to rodents, possibly through direct action on the brain. These observations prompted speculation that pharmacological inhibitors of ghrelin production would be valuable drugs for the treatment of obesity.

To study the physiological role of ghrelin, Wortley et al. generated ghrelin-deficient mice. Surprisingly, the mutant mice showed normal food intake, basal metabolic rate, and body weight. In contrast to wild-type mice, however, ghrelin-deficient mice on a high-fat diet burned more fat than carbohydrate, suggesting that ghrelin may play a role in regulating the metabolic substrates used for the maintenance of energy balance. In a complementary study, Sun et al. found that mice deficient in the receptor for ghrelin also showed no major abnormalities in food intake or body composition. Together, the studies indicate that ghrelin is not an essential regulator of appetite, and its role in body weight regulation may be more complex than previously envisaged. — PAK

Proc. Natl. Acad. Sci. U.S.A. 101, 8227; 4679 (2004)

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