Injection of cobalt protoporphyrin into the medial nuclei of the hypothalamus elicits weight loss.

Intracerebroventricular administration of small amounts (0.1 mumol/kg body wt) of cobalt protoporphyrin (CoPP), a synthetic analogue of heme, results in transient hypophagia and prolonged reduction in body weight of rats. Statistically significant hypophagia is detectable within 3 h of CoPP infusion. These changes are accompanied by prompt and sustained reductions in running wheel revolutions, a measure of spontaneous locomotor activity. Bilateral intrahypothalamic injections of CoPP at far lower doses (4 nmol/rat) resulted in similar findings following infusion into the paraventricular, dorsomedial, and ventromedial nuclei, but the compound had no such effect when injected into the thalamus or the lateral hypothalamic area. These effects were also observed following microinjection of the natural metalloporphyrin, heme, into the medial hypothalamic nuclei. Inorganic cobalt, iron, protoporphyrin, and magnesium protoporphyrin injected similarly were without such effect. These findings provide further evidence that the site of the previously described actions of CoPP in reducing food intake and body weight in rats resides, at least in part, in the medial hypothalamus. Furthermore, this study expands the spectrum of metalloporphyrins that act in the central nervous system to elicit these changes from synthetic compounds such as CoPP to heme, the natural, physiological metalloporphyrin.