Preproghrelin

Preproghrelin is the initial peptide product encoded by the human GHRL gene. It is a 117‑amino‑acid precursor that contains an N‑terminal signal sequence and serves as the precursor for ghrelin and obestatin, two peptide hormones derived from the same propeptide by tissue‑specific proteolytic processing. After translation, the signal peptide is removed to form proghrelin, which is cleaved to yield mature ghrelin (a 28‑amino‑acid peptide) and the C‑terminal‑derived obestatin; the exact processing and relative amounts can vary between tissues. Ghrelin requires acylation by ghrelin O‑acyltransferase (GOAT) on a serine residue to become active and to bind the growth hormone secretagogue receptor (GHSR). Desacyl ghrelin, the non‑acylated form, circulates in plasma and has effects that are still being clarified.

Ghrelin acts as an orexigenic hormone that stimulates appetite, promotes growth hormone release, and modulates gastric motility and glucose metabolism. Obestatin’s proposed functions have been controversial, and its physiological role remains uncertain. The GHRL gene is expressed most abundantly in the stomach, with additional expression in pancreas, hypothalamus, and other tissues. Ghrelin levels rise during fasting and fall after feeding, and alterations in the ghrelin/obestatin axis have been linked to metabolic disorders such as obesity and cachexia. Therapeutic research includes ghrelin receptor agonists and GOAT inhibitors, exploring potential treatments for appetite disorders and weight management.