Ghrelin

Ghrelin is a peptide hormone primarily produced by X/A-like cells in the fundus of the stomach, with smaller amounts found in other tissues such as the intestine. It was identified in 1999 as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). The ghrelin gene (GHRL) encodes a 117‑amino‑acid precursor that is cleaved to produce ghrelin and related products. The active form, acyl ghrelin, carries an n‑octanoyl modification on serine‑3, installed by the enzyme ghrelin O‑acyltransferase (GOAT). Desacyl ghrelin is the non‑acylated form circulating in blood and may have biological effects independent of GHS-R.

Ghrelin acts primarily through the GHS-R1a receptor, expressed in the pituitary and in several brain regions, notably the arcuate nucleus of the hypothalamus. Binding to GHS-R1a stimulates growth hormone release from the pituitary and promotes appetite, in part by activating neuropeptide Y and agouti‑related peptide neurons. Ghrelin levels rise before meals and fall after eating, contributing to meal initiation and energy balance.

Beyond appetite, ghrelin influences gastric motility and may affect glucose and lipid metabolism, insulin secretion, and cardiovascular function. Its secretion is regulated by nutritional status and body weight: fasting or caloric restriction raises ghrelin, while obesity is associated with lower fasting levels and blunted postprandial responses.

Clinical relevance includes research into ghrelin agonists for conditions like cancer‑related cachexia and other states of undernutrition, and ghrelin antagonists or inverse agonists have been explored for obesity. Examples of ghrelin receptor agonists include compounds used in clinical studies to mitigate weight loss and wasting.