Hypothalamic mechanism for cobalt protoporphyrin-induced hypophagia and weight loss: inhibition of the feeding response to NPY.

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.