Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake.
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.
Zhang
Jian V
JV
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305-5317, USA.
Ren
Pei-Gen
PG
Avsian-Kretchmer
Orna
O
Luo
Ching-Wei
CW
Rauch
Rami
R
Klein
Cynthia
C
Hsueh
Aaron J W
AJ
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D019295:Computational Biology; D017124:Conserved Sequence; D006224:Cricetinae; D004435:Eating / Q000187:drug effects; D005215:Fasting; D005746:Gastric Emptying / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects; D054439:Ghrelin; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D036361:Peptide Hormones / Q000097:blood / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D011485:Protein Binding; D011498:Protein Precursors / Q000235:genetics*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D054440:Receptors, Ghrelin; D015398:Signal Transduction; D015430:Weight Gain / Q000187:drug effects
C495797:GPR39 protein, human; D054439:Ghrelin; D008024:Ligands; D036361:Peptide Hormones; D011498:Protein Precursors; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; C505799:obestatin, human; C505798:obestatin, rat