Curtis-Prior P B, Oblin A R, Tan S
Int J Obes. 1980;4(2):111-9.
In rats allowed access to food, and in food-deprived rats, fenfluramine (20 and 100 mg kg-1) and amphetamine (10 and 20 mg kg-1) provoked a hypotriglyceridaemic effect. No changes in plasma cholesterol concentration were observed. The time course of the absorption of a lipid load differed according to the nutritional status of the animals; being bellshaped under fed, and curvilinear under fasted, conditions. However, absorption under both nutritional conditions was inhibited by amphetmine and fenfluramine. When rats which had received the test compounds were administered glycerol trioleate containing a tracer dose of glycerol [1-14C]-trioleate or [2-3H]-glycerol trioleate, there was an inhibition in the increase of plasma radioactivity only in the case when the fatty acid contained the radioactive label. The net effect of lipid absorption was a transfer of dietary lipid from the gut to adipose tissue stores. There was never more than 5 per cent of the administered load in the liver. These observations indicate that amphetamine and fenfluramine may have acute effects in reducing circulating triglycerides, separate from the effects on lipid absorption from the gut. In this latter, the palmitoyl-CoA monooleinacyltransferase enzyme probalby plays a key role and appears a major target of the overall anti-obesity of fenfluramine.
在可获取食物的大鼠以及食物剥夺的大鼠中，芬氟拉明（20和100毫克/千克）和苯丙胺（10和20毫克/千克）引发了降甘油三酯作用。未观察到血浆胆固醇浓度的变化。脂质负荷的吸收时间进程根据动物的营养状况而有所不同；在喂食条件下呈钟形，在禁食条件下呈曲线形。然而，在两种营养条件下的吸收均受到苯丙胺和芬氟拉明的抑制。当给接受了测试化合物的大鼠施用含有示踪剂量甘油[1-14C]-油酸甘油酯或[2-3H]-油酸甘油酯的甘油三油酸酯时，仅在脂肪酸含有放射性标记的情况下，血浆放射性的增加才受到抑制。脂质吸收的净效应是膳食脂质从肠道向脂肪组织储存的转移。肝脏中所含给药负荷从未超过5%。这些观察结果表明，苯丙胺和芬氟拉明在降低循环甘油三酯方面可能具有急性作用，这与它们对肠道脂质吸收的作用不同。在后者中，棕榈酰辅酶A单油酰转移酶可能起关键作用，并且似乎是芬氟拉明整体抗肥胖作用的主要靶点。
