Ghrelin is an orexigenic peptide hormone belonging to the motilin family. It is a well conserved 28 amino acid peptide generated by post-translational cleavage of the preproghrelin precursor protein (1).
Ghrelin is produced predominantly by endocrine X/A-like cells of the stomach submucosa, from where it is secreted into the plasma (1). It is also present in other parts of the gastrointestinal tract, while substantially lower amounts derive from other tissues including the pancreas. In pancreatic islets, ghrelin producing epsilon cells are primarily found during gestational development (2,3). After birth, epsilon cell numbers gradually decline (2,3).
Ghrelin circulates in two major forms: acyl-ghrelin, which possesses an n-octanoyl modification at Ser3, and des-acyl ghrelin without this modification (1). Des-acyl ghrelin is the predominant circulating form of ghrelin, although the lipid modification is required for binding to the growth hormone secretagogue receptor GHSR, which induces growth hormone release from the pituitary gland (1,3).
Ghrelin has an appetite stimulating effect, induces adiposity, and it regulates gastric acid secretion, gastrointestinal motility, and pancreatic glucose-stimulated insulin secretion. It also plays a crucial role in cardioprotection, muscle atrophy, bone metabolism and cancer (3,4).
Inhibitors of ghrelin have attracted enormous interest as potential anti-obesity therapeutic targets (5).