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Key Points Ghrelin is a peptide hormone derived from the stomach and gastrointestinal tract that predominantly controls energy balance and glucose homeostasis Ghrelin mainly affects metabolism through the G-protein-coupled growth hormone secretagogue receptor 1a (GHS-R1a) in the brain Pharmacologic ghrelin treatment in rodents leads to sustained gain of fat mass induced by increased food intake, decreased fat oxidation rates, altered nutrient partitioning, increased lipogenesis in adipose tissue and decreased thermogenesis Ghrelin-deficient mouse models possess improved peripheral insulin sensitivity, and descriptive studies in humans and rodents suggest an inverse relationship between plasma ghrelin levels and insulin resistance and type 2 diabetes Constituting a classical combination of a peptide hormone and a G-protein-coupled receptor (with additional ligands and receptors possibly to be discovered), there is reasonable potential to target the ghrelinGHS-R system pharmacologically, whereas possible GHS-R1a-independent ghrelin effects represent a less defined and more complicated target This is a preview of subscription content, access via your institution Access options Subscribe to this journal Receive 12 print issues and online access $189.00 per year only $15.75 per issue Buy this article Purchase on SpringerLink Instant access to the full article PDF