Galbraith R A, Kappas A
Rockefeller University Hospital, New York, New York 10021.
Am J Physiol. 1991 Dec;261(6 Pt 2):R1388-94. doi: 10.1152/ajpregu.1991.261.6.R1388.
Cobalt protoporphyrin (CoPP) in single subcutaneous doses produces prolonged weight loss in adult and aged male rats. The altered body weight level in treated animals is actively defended against starvation or overfeeding over prolonged time periods (greater than 50-100 days). The actions of CoPP on appetite and body weight regulation are biphasic, comprising an initial period of hypophagia, probably mediated centrally, until a particular body weight level is attained. Resumption of normal calorie intake follows, although lowered body weight levels are sustained, suggesting an additional action of the compound on peripheral substrate metabolism. Controlled decrements in body weight can be produced by repetitive low-dose CoPP treatment (e.g., 1 mumol/kg body wt weekly); low-dose regimens do not elicit altered hormonal homeostasis or aberrations in heme/cytochrome P-450 regulation that have been observed following larger doses (25-50 mumol/kg body wt) of the compound. CoPP may be a valuable probe with which to explore the role of heme-related molecules in the regulation of appetite and body weight.
单次皮下注射钴原卟啉（CoPP）会使成年和老年雄性大鼠体重持续减轻。在较长时间段（超过50 - 100天）内，经处理的动物体重改变水平能有效抵御饥饿或过度喂养。CoPP对食欲和体重调节的作用具有双相性，包括初期的摄食减少，可能是由中枢介导，直至达到特定体重水平。之后恢复正常热量摄入，尽管体重水平仍维持在较低状态，这表明该化合物对外周底物代谢还有额外作用。通过重复低剂量CoPP处理（例如，每周1 μmol/kg体重）可实现体重的可控下降；低剂量方案不会引发如大剂量（25 - 50 μmol/kg体重）该化合物后所观察到的激素稳态改变或血红素/细胞色素P - 450调节异常。CoPP可能是一种有价值的探针，可用于探索血红素相关分子在食欲和体重调节中的作用。
