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Science 11 November 2005:
Vol. 310. no. 5750, pp. 996 - 999
DOI: 10.1126/science.1117255
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Research Articles

Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake

Jian V. Zhang, Pei-Gen Ren, Orna Avsian-Kretchmer, Ching-Wei Luo, Rami Rauch, Cynthia Klein, Aaron J. W. Hsueh*

Ghrelin, a circulating appetite-inducing hormone, is derived from a prohormone by posttranslational processing. On the basis of the bioinformatic prediction that another peptide also derived from proghrelin exists, we isolated a hormone from rat stomach and named it obestatin—a contraction of obese, from the Latin "obedere," meaning to devour, and "statin," denoting suppression. Contrary to the appetite-stimulating effects of ghrelin, treatment of rats with obestatin suppressed food intake, inhibited jejunal contraction, and decreased body-weight gain. Obestatin bound to the orphan G protein–coupled receptor GPR39. Thus, two peptide hormones with opposing action in weight regulation are derived from the same ghrelin gene. After differential modification, these hormones activate distinct receptors.

Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305–5317, USA.

* To whom correspondence should be addressed: E-mail: aaron.hsueh{at}stanford.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)