neuropeptide-y and cobaltiprotoporphyrin

Cobalt protoporphyrin (CoPP) reduces food intake and body weight following intracerebroventricular (i.c.v.) administration in rats. We injected 0.2 mumol CoPP per kg body weight i.c.v. and monitored body weight and daily food intake for 7 days. The body weight and 24 h food intake of CoPP-treated animals was significantly lower than that of vehicle-treated animals in all studies (P < 0.01) from day 2 to day 7. The 2 h feeding response (CoPP vs. vehicle-treated) to 10 micrograms neuropeptide Y (NPY) (4.0 vs. 7.1 g; P < 0.05), the 1 h feeding response to 10 micrograms galanin (1.3 vs. 3.2 g; P < 0.05) and 30 micrograms norepinephrine (0.6 vs. 1.9 g; P < 0.05) in CoPP-treated animals were all reduced compared to the vehicle-treated group. In addition there was no change in hypothalamic NPY mRNA in CoPP-treated animals. I.c.v. CoPP decreases sensitivity to exogenous NPY, galanin and norepinephrine. The effect of CoPP is not specific to NPY as previously described.

Topics: Animals; Eating; Male; Neuropeptide Y; Protoporphyrins; Rats; Rats, Wistar; Weight Loss

The administration of cobalt protoporphyrin results in transient decreases in food intake and prolonged weight loss in rats. After IVC injection of cobalt protoporphyrin, the food intake of treated rats falls to 10% of vehicle-treated control rats within 48 h. At the same time, the concentrations of mRNA for neuropeptide Y increase approximately twofold in the hypothalamus. The failure of these animals to display a feedings response to elevation of endogenous NPY concentration is mimicked by their failure to respond to exogenous. ICV injections of neuropeptide Y. Because NPY binding studies are confounded by high nonspecific binding, radiolabeled PYY was used to measure binding to hypothalamic membranes and for autoradiography with hypothalamic sections. No abnormalities in the number of receptors or the affinity of the binding interaction were noted. In addition, hypothalamic concentrations of cyclic AMP were unchanged following treatment with either cobalt protoporphyrin or NPY. These results indicate that the locus of the failure of CoPP-treated animals to feed after administration of NPY must be either distal to, or unrelated to, the NPY receptor in the hypothalamus.

Topics: Animals; Brain Mapping; Cyclic AMP; Eating; Hypothalamus; Injections, Intraventricular; Male; Neuropeptide Y; Protoporphyrins; Rats; Rats, Sprague-Dawley; Receptors, Neuropeptide Y; Synaptic Membranes

Topics: Animals; Female; Hypothalamus; Insulin; Insulin Secretion; Male; Mutation; Neuropeptide Y; Obesity; Protoporphyrins; Rats; Rats, Mutant Strains; RNA, Messenger

The mechanism whereby neurally or peripherally administered cobalt-protoporphyrin (CoPP) leads to transient hypophagia and prolonged weight reduction in normal and genetically obese animals is unknown. Neuropeptide Y (NPY) is a known endogenous stimulator of feeding behavior and is elevated in the hypothalamus of food-deprived rats. Accordingly, we examined the interaction between CoPP and NPY in the central nervous system. Concentrations of NPY mRNA in the hypothalami of rats treated intracerebroventricularly with vehicle or CoPP responded to decreased food intake with comparable increases. However, intracerebroventricular infusions of NPY elicited increased intake of food in vehicle-treated rats but were without effect in CoPP-treated animals. The results suggest that CoPP acts, at least in part, by blocking the feeding response to NPY.

Topics: Animals; Blotting, Northern; Feeding Behavior; Food Deprivation; Gene Expression; Hypothalamus; Male; Microinjections; Neuropeptide Y; Protoporphyrins; Rats; Rats, Sprague-Dawley; RNA, Messenger; Weight Loss