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

• Published in: Science (American Association for the Advancement of Science) Vol. 310; no. 5750; pp. 996 - 999
• Main Authors: Zhang, Jian V., Ren, Pei-Gen, Avsian-Kretchmer, Orna, Luo, Ching-Wei, Rauch, Rami, Klein, Cynthia, Aaron J. W. Hsueh
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 11.11.2005; The American Association for the Advancement of Science
• Subjects: Amino Acid Sequence; Analysis; Analytical, structural and metabolic biochemistry; Animals; Antibodies; Biological and medical sciences; Body Weight; CHO Cells; Computational Biology; Conserved Sequence; Cricetinae; Eating - drug effects; Fasting; Food intake; Food science; Fractions; Fundamental and applied biological sciences. Psychology; Gastric Emptying - drug effects; Gastrointestinal Motility - drug effects; Gene expression regulation; Genes; Ghrelin; Hormonal regulation; Hormones; Humans; In Vitro Techniques; Ligands; Literary Devices; Male; Males; Medical research; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Obesity; Orphans; Peptide hormones; Peptide Hormones - blood; Peptide Hormones - chemistry; Peptide Hormones - genetics; Peptide Hormones - metabolism; Peptide Hormones - pharmacology; Peptide Hormones - physiology; Peptides; Protein Binding; Protein hormones. Growth factors. Cytokines; Protein Precursors - genetics; Proteins; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptors; Receptors, G-Protein-Coupled - metabolism; Receptors, Ghrelin; Scientific Concepts; Signal Transduction; Stomach; Weight Gain - drug effects; Appetite; Vertebrata; Mammalia; Gene; Rat; Ghrelin; Animal; Peptide hormone; Rodentia; Genetics; Anorectic; Appetite stimulant
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1117255

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.