Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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CHO Cells
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Computational Biology
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Conserved Sequence
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Cricetinae
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Eating* / drug effects
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Fasting
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Gastric Emptying / drug effects
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Gastrointestinal Motility / drug effects
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Ghrelin
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Humans
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In Vitro Techniques
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Ligands
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Male
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Peptide Hormones / blood
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Peptide Hormones / chemistry
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Peptide Hormones / genetics*
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Peptide Hormones / metabolism
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Peptide Hormones / pharmacology
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Peptide Hormones / physiology*
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Protein Binding
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Protein Precursors / genetics*
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Radioimmunoassay
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Rats
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Rats, Sprague-Dawley
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Receptors, G-Protein-Coupled / metabolism
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Receptors, Ghrelin
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Signal Transduction
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Weight Gain / drug effects
Substances
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GPR39 protein, human
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Ghrelin
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Ligands
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Peptide Hormones
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Protein Precursors
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Receptors, G-Protein-Coupled
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Receptors, Ghrelin
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obestatin, human
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obestatin, rat