Intracisternal des-acyl ghrelin inhibits food intake and non-nutrient gastric emptying in conscious rats

Although des-acyl ghrelin is thought of as a non-functional peptide, studies show that it decreases food intake and gastric emptying in mice. However, no studies have examined the effects of centrally administered des-acyl ghrelin on food intake and gastrointestinal transit in rats. We investigated the effects of intracisternal (IC) administration of des-acyl ghrelin on food intake in free-feeding and food-deprived rats, as well as on the gastrointestinal transit in conscious rats. IC injection of des-acyl ghrelin dose-dependently (0.1 and 1.0 nmol/rat) decreased 20-min, 1-h and 2-h cumulative food intake in 16-h food-deprived, but not free-feeding rats, while IC administration of O-n-octanoylated (acylated) ghrelin (1 nmol/rat) increased food intake in both fed and fasted rats. IC-administered des-acyl ghrelin dose-dependently inhibited charcoal semi-liquid gastric emptying (0.01, 0.1, 0.3 and 1.0 nmol/rat) compared to saline-injected controls, but did not affect the geometric center and running percentage of small intestinal transit. However, IC acylated ghrelin enhanced gastric emptying and geometric center of small intestinal transit, but did not change running percentage of small intestinal transit. The studies suggest that IC des-acyl ghrelin decreases food intake in food-deprived rats and inhibits gastric emptying without altering small intestinal transit. These results establish the role of des-acyl ghrelin in regulating food intake as well as gastric emptying.