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

TLDR

Ghrelin is a circulating appetite‑stimulating hormone produced by post‑translational processing of a prohormone. The authors sought to isolate and identify a novel peptide, obestatin, predicted to be derived from the same proghrelin precursor. They isolated obestatin from rat stomach based on bioinformatic prediction of a proghrelin‑derived peptide. Obestatin suppresses food intake, inhibits jejunal contraction, reduces body‑weight gain, binds the orphan GPCR GPR39, and opposes ghrelin’s actions, showing that two opposing peptides arise from the same gene.

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.