Ghrelin: A Molecular Target for Weight Regulation, Glucose and Lipid Metabolism

Flavia      Prodam; Simonetta      Bellone; Ginevra      Corneli; Graziella      Golisano; Gianni      Bona

Abstract

Ghrelin, a peptide predominantly produced by the stomach, was discovered as natural ligand of the Growth Hormone Secretagogue receptor type 1a (GHS-R1a) and was anticipated to play major role in the control of somatotroph function. Ghrelin progressively turned out to exert pleiotropic actions on several endocrine and non endocrine target tissues. Particular attention has focused on its central orexigenic effect and weight control, and more recently on its peripheral metabolic actions on insulin secretion and insulin sensitivity, glucose and lipid metabolism. Ghrelin circulates in two forms, acylated (AG) and unacylated (UAG). Interestingly, some metabolic actions of ghrelin are independent of its acylation, which is necessary for it to bind and activate the GHS-R1a, supporting the hypothesis of the existence of several ghrelin receptor subtypes involved in the control of metabolic functions and pancreatic cell survival. Recent data have introduced the hypothesis that the ghrelin system plays a role in polygenic obesity, type 2 diabetes, metabolic syndrome, atherogenesis, and β-cell survival in type 1 diabetes. Many experimental studies have recently tried to inhibit or amplify ghrelin secretion for the treatment of obesity and wasting syndromes, respectively. This review recapitulates what is known about ghrelin chemical structure, GHS-R1a and the putative unknown receptor subtypes, AG and UAG involvement in the control of feeding, weight, glucose and lipid metabolism, and the recently patented molecules that modulate the pleiotropic actions of the ghrelin system.

Keywords: Ghrelin, acylated ghrelin, unacylated ghrelin, GHS receptor, obesity, wasting syndrome, diabetes, glucose metabolism, lipid metabolism, food intake