Cobalt-Protoporphyrin Suppresses Expression of Genetic Obesity in Homozygous (fa/fa) Zucker Rats

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Abstract
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 (≈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.