Ghrelin gets hungry

Intriguingly, plasma ghrelin concentrations rise progressively during fasting and fall to a nadir within an hour of eating.7 The possibility that high ghrelin concentrations might trigger feeding has been confirmed, at least in rodents, in which ghrelin administration into the cerebral ventricles or periphery induced eating and weight gain.8,9 This effect seems to be mediated, at least in part, via stimulation of a population of arcuate nucleus neurons, which coexpress two orexigenic peptides-neuropeptide Y (NPY) and agouti-- related protein (AGRP).10,11 Although it might seem improbable that peptides as large as ghrelin (3315 Da) could reach these neurons, the basal hypothalamus has a selectively permeable blood-brain barrier that allows entry of circulating peptides from blood, and is also accessible to peptides carried in the cerebrospinal fluid. In rats, the orexigenic effect of ghrelin is powerful-on a par with that of NPY, generally viewed as one of the most potent of central appetite stimulants.11 Moreover, ghrelin-induced hyperphagia is sustained during continued administration and leads ultimately to obesity. Ghrelin also stimulates appetite in human beings, inducing subjective hunger and increasing food intake when administered intravenously in healthy people.12,13 Ghrelin is the first gut-brain peptide proven to have orexigenic properties in people, although numerous peptides affect appetite or eating behaviour in rodents.