Figure 1.

Illustration describing how peripherally produced ghrelin likely gains access to the brain. Ghrelin is primarily produced and secreted by the stomach although the small intestine and pancreas likewise produce a small quantity. Ghrelin O-acyltransferase (GOAT) converts des-acylated into its active acylated form capable of activating growth hormone secretagogue receptor (GHSRs) while esterases cleave acylated ghrelin’s O-octanoyl moiety returning it to its predominant inactive des-acylated ghrelin form (90% of total circulating ghrelin). Although des-acylated ghrelin is capable of crossing the blood brain barrier from the blood into the brain, acylated ghrelin demonstrates a very limited ability to do so (depicted by blue X). Accordingly, acylated ghrelin either stimulates GHSR on vagal afferents or bypasses the blood brain barrier (BBB) and activates GHSRs in or around circumventricular organs to convey its orexigenic effects. AP, area postrema; ARC, arcuate nucleus; ME, median eminence; NTS, nucleus tractus solitaries; SFO, subfornical organ.