Ghrelin receptor in energy homeostasis and obesity pathogenesis.

The ghrelin receptor, also known as growth hormone secretagogue receptor (GHS-R), was identified in porcine and rat anterior pituitary membranes, where the synthetic secretagogue MK-0677 causes amplified pulsatile growth hormone (GH) release. In addition to its function in the stimulation of GH secretion, ghrelin, the natural ligand of ghrelin receptor is now recognized as a peptide hormone with fundamental influence on energy homeostasis. Despite the potential existence of multiple subtypes of ghrelin receptor, the effects of ghrelin on energy metabolism, obesity, and diabetes are mediated by its classical receptor GHS-R1a, whose activation requires the n-octanoylation of ghrelin. Here we review the current understanding of the role of the ghrelin receptor in the regulation of energy homeostasis. An overview of the ghrelin receptor is presented first, followed by the discussion on its effects on food intake, glucose homeostasis, and lipid metabolism. Finally, potential strategies for treating obesity and diabetes via manipulation of the ghrelin/ghrelin receptor axis are explored.