At the cutting edge: Ghrelin gene products in food intake and gut motility

Ghrelin, a 28-amino acid peptide, was recently identified from the stomach as the first endogenous ligand for growth hormone secretagogue receptors (previously known as orphan receptors). Ghrelin was discovered by 'reverse pharmacology'. The acyl ghrelin peptide features a unique post-translational modification of O-n-octanoylation at serine 3, and is the only gastrointestinal signal that increases meal size. However, des-acyl ghrelin accounts for the major forms in the plasma. Most recently, obestatin, a novel 23-amino acid peptide, was derived from the mammalian preproghrelin gene, which also encodes ghrelin, by a bioinformatic approach. This at-the-cutting-edge review focuses on three ghrelin gene products: acyl ghrelin, des-acyl ghrelin, and the newly identified obestatin. Their updated orexigenic and anorexigenic effects on food intake, their signal transduction pathways from the periphery to the brain, as well as their roles in modulating gastrointestinal motility, and potential applications in the many fields of medicine such as eating disorders, obesity/anorexia-cachexia, and gastrointestinal dysmotility under different conditions, are critically addressed.