The mode of action of fenfluramine and its derivatives and their effects on glycerolipid metabolism

Abstract

SummaryThe evidence is reviewed that fenfluramine and benfluorex could have both direct and indirect effects in decreasing the rate of triacylglycerol synthesis in the liver. The direct effect is mediated through the inhibition of phosphatidate phosphohydrolase and by the recycling of excess phosphatidate back to glycerol phosphate. The indirect effect involves alteration of the concentrations of glucocorticoids in the blood and this was demonstrated with rats treated chronically with benfluorex. In these animals, the extent of ethanol-induced increases in serum corticosterone, in hepatic phosphatidate phosphohydrolase activity, and in the synthesis and accumulation of triacylglycerol in the liver was diminished. It is also suggested that glucocorticoids are responsible for the increased synthesis of hepatic triacylglycerols that is seen in diabetes and in stress conditions, and after eating fructose, glycerol, sorbitol and saturated fat. A combination of these direct and indirect effects could contribute...