METABOLIC AND OREXIGENIC EFFECTS OF INTRACEREBROVENTRICULAR NEUROPEPTIDE-Y ARE ATTENUATED BY FOOD-DEPRIVATION

Administration of neuropeptide Y (NPY) into the hypothalamus or cerebr al ventricles has been shown to increase food intake, the secretion of hormones such as insulin, glucagon and corticosterone and to alter th e metabolism of carbohydrate and lipids, It has been suggested that me tabolic effects of hypothalamic NPY may contribute to fat accretion in some types of obesity and to the metabolic and behavioural adaptation to food deprivation. However, it is currently unknown ii different nu tritional states alter the responses to hypothalamic NPY. Consequently , we have compared the effects of NPY injected into the third ventricl e (ICV) in the fed and overnight-fasted state on ingestive behaviour, on insulin, glucagon and corticosterone secretion before, and followin g, an IV glucose bolus (IVGTT) and on blood glucose following an intra -arterial insulin bolus (ITT), Studies were performed on conscious, un restrained adult female rats, In the fed state, 2 and 6 mu g ICV NPY p roduced a potent orexigenic and dypsogenic effect. In the fasted state , the 2 mu g dose had a dypsogenic effect, while only the 6 mu g dose had a significant orexigenic effect. In the fed but not fasted state, 3 mu g ICV NPY increased plasma glucagon and corticosterone levels and attenuated the decline in blood glucose during the ITT, By contrast, in both fed and fasted groups, 3 mu g ICV NPY potentiated the insulin secretory response during the IVGTT, We conclude that, apart from stim ulating insulin secretion, the acute metabolic and orexigenic response s to ICV NPY in this study were substantially reduced or abolished by overnight fasting. Therefore, behavioural and metabolic responses to e ndogenous hypothalamic NPY may also be more significant in the fed tha n the fasted state.