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.
Galbraith
R A
RA
Rockefeller University Hospital, New York, N.Y.
Kappas
A
A
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D009765:Obesity / Q000235:genetics*; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011924:Rats, Zucker
D011524:Protoporphyrins; C007095:cobaltiprotoporphyrin