Update on ghrelin.

Abstract

Few peptide hormones have attracted as much attention of the scientific community as ghrelin, the natural secretagogue for growth hormone (GH) identified by M. Kojima et al. in 1999 [1], resulting in more than 4000 PubMed citations over the last ten years. The initial interest can be attributed to the ability of ghrelin to stimulate feeding in mammals, suggesting it as a potential target for the development of antiobesity drugs. Many studies investigating this issue have however revealed the complexity of the ghrelin system including the differential physiological effects of the three peptide products of the ghrelin gene: ghrelin, which is peri-translationally modified via acylation with the octanoic acid; des-acyl ghrelin that is not acylated or has lost its fatty acid residue; and obestatin, another bioactive peptide derived from the preproghrelin precursor. Most importantly, it has been realized that beside stimulation of GH secretion and increased feeding, ghrelin has multiple biological effects that would be important to preserve if aiming to antagonize ghrelin-mediated positive energy balance. Among these functions, ghrelin was found to regulate gastrointestinal motility and associated sensory functions, to modulate the reproductive and stress axes, mood and emotion, glucose metabolism, as well as affecting the cardiovascular system and renal function.