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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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Comment on "Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake".
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Science 315, 766c
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Response to Comment on "Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake".
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J. Endocrinol. 192, 313-323
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Exercise and Humoral Mediators of Peripheral Energy Balance: Ghrelin and Adiponectin.
R. R. Kraemer and V. D. Castracane (2007)
Experimental Biology and Medicine 232, 184-194
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{alpha}-Cells of the Endocrine Pancreas: 35 Years of Research but the Enigma Remains.
J. Gromada, I. Franklin, and C. B. Wollheim (2007)
Endocr. Rev. 28, 84-116
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Normal Food Intake and Body Weight in Mice Lacking the G Protein-Coupled Receptor GPR39.
F. Tremblay, M. Perreault, L. D. Klaman, J. F. Tobin, E. Smith, and R. E. Gimeno (2007)
Endocrinology 148, 501-506
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GPR39 Signaling Is Stimulated by Zinc Ions But Not by Obestatin.
B. Holst, K. L. Egerod, E. Schild, S. P. Vickers, S. Cheetham, L.-O. Gerlach, L. Storjohann, C. E. Stidsen, R. Jones, A. G. Beck-Sickinger, et al. (2007)
Endocrinology 148, 13-20
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Effects of Obestatin on Energy Balance and Growth Hormone Secretion in Rodents.
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J. Clin. Endocrinol. Metab. 92, 229-234
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Exendin-4 Potently Decreases Ghrelin Levels in Fasting Rats.
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Diabetes 56, 143-151
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Obestatin acts in brain to inhibit thirst.
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Am J Physiol Regulatory Integrative Comp Physiol 292, R637-R643
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H. S. Sallam, H. M. Oliveira, H. T. Gan, D. N. Herndon, and J. D. Z. Chen (2007)
Am J Physiol Regulatory Integrative Comp Physiol 292, R253-R257
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On the Processing of Proghrelin to Ghrelin.
X. Zhu, Y. Cao, K. Voodg, and D. F. Steiner (2006)
J. Biol. Chem. 281, 38867-38870
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Endocr. Rev. 27, 719-727
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Diabetes 55, S92-S97
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J. Endocrinol. 191, 481-489
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A. J. Walley, A. I.F. Blakemore, and P. Froguel (2006)
Hum. Mol. Genet. 15, R124-R130
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J. O. L. Jorgensen (2006)
J. Clin. Endocrinol. Metab. 91, 3279-3280
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From the Cover: Vaccination against weight gain.
E. P. Zorrilla, S. Iwasaki, J. A. Moss, J. Chang, J. Otsuji, K. Inoue, M. M. Meijler, and K. D. Janda (2006)
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J. Endocrinol. 190, 7-10
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