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.