Role of ghrelin gene-derived peptides in the control of energy balance and cardiometabolic homeostasis

Abstract

The human GHRL gene encodes a 117-aminoacid peptide, preproghrelin that is proteolytically processed to yield two peptides: ghrelin and obestatin. Ghrelin is secreted to the bloodstream in two major forms, acylated ghrelin (with an n-octanoylation in the third serine residue) and desacyl ghrelin (the form lacking n-octanoylation). Ghrelin acylation, promoted by ghrelin O-acyltransferase (GOAT), is essential for binding to the growth hormone (GH) secretagogue receptor (GHS-R) 1a and for the main endocrine functions of acylated ghrelin, including the stimulation of GH release, induction of food intake and stimulation of adipogenesis. Although devoid of binding to GHS-R 1a, desacyl ghrelin also displays orexigenic and adipogenic actions, whereas the role of obestatin in the regulation of energy balance remains unclear. The discovery of the widespread distribution of ghrelin and its receptor in the cardiovascular system opened a new research field in the role of ghrelin in the control of blood pressure and myocardial function. Indeed, ghrelin inhibits the apoptosis of cardiomyocytes and endothelial cells, ameliorates left ventricular function and reduces fibrosis after myocardial injury in experimental models. In humans, ghrelin improves endothelial function by increasing nitric oxide (NO) bioavailability, normalizes the altered balance between endothelin-1 and NO in patients with metabolic syndrome and exerts performance-enhancing effects on myocardial function of patients with chronic heart failure. This review focuses on advances in cardiometabolic effects of ghrelin gene-derived products in rodents and humans, and the possible role of ghrelin as a therapeutic molecule for treating cardiometabolic diseases. Adipobiology 2011; 3: 21-30.