Ghrelin: an orexigenic signal from the stomach

Abstract

Introduction The discovery of ghrelin, a 28 amino-acid peptide hormone, has generated a substantial amount of attention for a number of reasons. Initially, ghrelin was heralded as the long sought endogenous ligand for the orphan growth hormone secretagogue receptors (GHS-Rs). Indeed, like growth hormone secretagogues (GHS), ghrelin targeted these receptors to potently increase the release of growth hormone (GH) both in vitro and in vivo. Soon, however, it became evident that ghrelin was implicated in a variety of physiological processes that include cell proliferation, metabolism, cell protection, reproduction, etc. Of these, the effects of ghrelin on food intake and metabolism have had the biggest impact; unlike other peripheral signals associated with energy balance, ghrelin increases appetite and leads to the accumulation of body fat. Indeed, the stimulatory effects of ghrelin on food intake and its apparent opposite relation to the anorectic hormone, leptin, have been proposed as the ying/yang model for hormonal regulation of energy balance. Nevertheless, the more is known about ghrelin, the more it becomes obvious that ghrelin produces its metabolic effects via a multitude of central and peripheral mechanisms that work in parallel to modulate the effects of ghrelin in energy regulation. This chapter will review the literature regarding the effects of ghrelin on energy balance. Energy balance implies the regulation of both food intake and energy expenditure, therefore we will discuss both topics in relation to ghrelin. A description of the possible central routes of ghrelin actions on energy balance within the brain will follow.