Appetite and gastrointestinal motility: Role of ghrelin-family peptides

Eating disorders, obesity and cachexia endanger the lives of millions of people worldwide. Fortunately, in last decade, there has been a rapid and substantial progress toward uncovering the molecular and neural mechanisms by which energy imbalance develops. In 1999, ghrelin was identified as the first orexigenic gut-derived peptide. It stimulates appetite and controls the gastric motility and the acid secretion through the activation of the growth hormone secretagogue-receptor. After the discovery of ghrelin, other forms of ghrelin-related proteins were isolated from the rat stomach. The unmodified des-n-octanoyl form (des-acyl ghrelin) and the recent obestatin act through distinct receptors and contrarily to acyl ghrelin, show an anorexigenic activity. The finding that these three peptide hormones derive from the same precursor exert opposing physiological actions, highlights the importance of post-translational regulatory mechanisms. Further investigations are required to highlight the complexity of ghrelin physiology in order to better understand the mechanisms regulating the energy balance and provide a successful treatment of eating disorders, obesity and cachexia. (C) 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.