Galbraith R A, Kappas A
Rockefeller University Hospital, New York, NY 10021.
Proc Natl Acad Sci U S A. 1989 Oct;86(19):7653-7. doi: 10.1073/pnas.86.19.7653.
Cobalt-substituted protoporphyrin administered subcutaneously to normal adult rats elicited prompt decreases in food intake and sustained decreases in body weight. Repetitive parenteral administration of small doses of this synthetic heme analogue resulted in dose-related diminutions of carcass fat content without changes in carcass protein content. Direct injection of the compound into the third ventricle of the brain produced changes in food intake and body weight that were quantitatively similar to those observed after parenteral treatment but required only 1-2% of the parenteral dose. The effects of intracerebroventricularly administered cobalt protoporphyrin on body weight were dose-related and were not produced by inorganic cobalt, heme, and a number of other metal-substituted protoporphyrins. Differential body weights between control and treated animals persisted for at least 300 days after intracerebroventricular injections of a single dose (0.2 or 0.4 mumol/kg of body weight) of the compound. Similar effects were observed after subcutaneous administration of the metalloporphyrin to genetically obese Zucker (fa/fa) rats and normal and genetically obese (ob/ob) mice as well as chickens and dogs. Cobalt-substituted mesoporphyrin elicited comparable effects on food intake and body weight. The results of these studies define a new biological action of cobalt protoporphyrin and demonstrate that this and certain other cobalt porphyrins can act, at least in part, in the central nervous system to regulate appetite and to produce long-sustained diminutions in body weight and carcass content of fat in animals.
给正常成年大鼠皮下注射钴取代原卟啉后，食物摄入量迅速减少，体重持续下降。重复小剂量肠胃外给予这种合成血红素类似物会导致与剂量相关的胴体脂肪含量减少，而胴体蛋白质含量无变化。将该化合物直接注射到脑第三脑室会引起食物摄入量和体重的变化，其在数量上与肠胃外给药后观察到的变化相似，但所需剂量仅为肠胃外给药剂量的1 - 2%。脑室内给予钴原卟啉对体重的影响与剂量相关，且无机钴、血红素及其他多种金属取代原卟啉不会产生这种影响。在脑室内注射单剂量（0.2或0.4 μmol/kg体重）该化合物后，对照动物与处理动物之间的体重差异持续至少300天。给遗传性肥胖的 Zucker（fa/fa）大鼠、正常及遗传性肥胖（ob/ob）小鼠以及鸡和狗皮下注射金属卟啉后也观察到类似效果。钴取代中卟啉对食物摄入量和体重产生了类似影响。这些研究结果定义了钴原卟啉的一种新生物学作用，并证明这种及某些其他钴卟啉至少可部分作用于中枢神经系统，以调节食欲，并使动物体重和胴体脂肪含量长期持续下降。
