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Ghrelin
A 28-amino acid peptide hormone primarily produced by the stomach that stimulates appetite, growth hormone release, and energy metabolism, often called the 'hunger hormone.'
Overview
Ghrelin is a 28-amino acid peptide hormone discovered in 1999 by Masayasu Kojima and colleagues at Kurume University in Japan. It was identified as the endogenous ligand for the previously orphaned growth hormone secretagogue receptor (GHS-R1a), now known as the ghrelin receptor. Ghrelin is unique among peptide hormones in that it requires octanoylation (attachment of an octanoic acid fatty acid chain to serine-3) for its biological activity — a post-translational modification catalyzed by the enzyme ghrelin O-acyltransferase (GOAT).
Ghrelin is primarily produced by X/A-like enteroendocrine cells in the gastric fundus, though it is also expressed in the small intestine, pancreas, brain, and other tissues. Plasma ghrelin levels rise during fasting and fall after eating, establishing it as a key hunger signal. Ghrelin acts on the hypothalamic arcuate nucleus to stimulate NPY/AgRP neurons, promoting appetite and food intake. It is the only known circulating hormone that stimulates appetite (orexigenic), counterbalancing the anorexigenic effects of leptin, insulin, and PYY.
Beyond appetite regulation, ghrelin is a potent stimulator of growth hormone release from the pituitary gland. In fact, it was identified through its GH-releasing activity before its appetite-stimulating role was fully characterized. Ghrelin also has metabolic effects including promoting adipogenesis and glucose metabolism, cardiovascular effects including cardioprotection and vasodilation, and anti-inflammatory properties.
Clinical interest in ghrelin has been substantial. Elevated ghrelin levels are observed in conditions associated with energy deficit (anorexia nervosa, cachexia, fasting), while ghrelin levels are paradoxically low in obesity (though the reasons remain debated). Ghrelin agonists have been investigated for cancer-related cachexia, post-surgical ileus, and growth hormone deficiency, while ghrelin antagonists and vaccine approaches have been explored for obesity treatment.