Basic nutritional investigationIntracerebroventricular O-n-octanoylated ghrelin and its splice variant-induced feeding is blocked by insulin, independent of obestatin or CRF receptor, in satiated rats

ObjectiveThe purpose of this study was to investigate the impact of intracerebroventricular (ICV) injection of the two endogenous forms of acyl ghrelin, O-n-octanoylated ghrelin and des-Gln14-ghrelin, on feeding behavior, as well as their interactions with insulin, obestatin, and corticotropin-releasing factor receptor (CRF-R) antagonist in the forebrain to influence food intake.MethodsWe examined the food intake in conscious, freely fed rats, which were chronically implanted with ICV catheters.ResultsO-n-octanoylated ghrelin and des-Gln14-ghrelin (0.1 nmol/rat) were equally potent in stimulating food intake in freely fed rats, up to 8 h after ICV injection (P < 0.05). In contrast, ICV administration of insulin (8 mU/rat), obestatin (2 nmol/rat), and astressin (2 nmol/rat), a specific CRF-R antagonist, did not modify feeding in freely fed rats. Furthermore, pretreatment with ICV insulin (P < 0.01), but not obestatin or astressin, at the abovementioned dose, blocked central acyl-ghrelin-induced hyperphagic effects.ConclusionICV O-n-octanoylated ghrelin and its splice variant, des-Gln14-ghrelin, are equally potent to elicit food intake in freely fed rats, while these feeding-stimulating effects are opposed by insulin, but independent of obestatin and endogenous CRF-R in the forebrain.