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 (≈ 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 ihe phenotype of the homozygous. obese Zucker rat is changed to that of its lean littermate. © 1990 S. Karger AG, Basel.