Cobalt-protoporphyrin suppresses expression of genetic obesity in homozygous (fa/fa) Zucker rats.

Profound obesity is conferred on the Zucker rat by homozygosity for a recessive gene (fa/fa); the heterozygous animal is lean. Subcutaneous administration of the heme analogue cobalt-protoporphyrin produces a long-sustained reduction in body weight of the homozygous Zucker rat. Intracerebroventricular injection of the compound, in a single small dose, results in an extremely prolonged (approximately 300 days) lowering of the 'set point' for body weight regulation, confirming a central nervous system action of the metalloporphyrin. The effect of cobalt-protoporphyrin is so pronounced that the phenotype of the homozygous, obese Zucker rat is changed to that of its lean littermate.