Studies on the ethanol-induced changes in glycerolipid synthesis in rats and their partial reversal by N-(2-benzoyloxyethyl)norfenfluramine (benfluorex)

Abstract

Rats were treated daily for 5 days with benfluorex (S-780) 50 mg kg−1 and 2 h after the fifth treatment were intubated with ethanol 5 g kg−1 or with isocaloric glucose. S-780 did not alter the absorption or oxidation of [1-14C]ethanol nor did it decrease the concentration of ethanol and its water soluble metabolites in the tissues examined. The rate of hepatic glycerolipid synthesis was measured in vivo using [14C]palmitate and [3H]glycerol and the accumulation of [14C]palmitate in various tissues was determined 4 h after intravenous injection. Ethanol treatment increased the relative rate of TG† synthesis in the liver and decreased the synthesis of PC, PE and PS + PI. The relative flux from PA to DG and TG was increased. These changes were reflected in the accumulation of [14C]palmitate in hepatic lipids and were obtained under conditions where the net rate of [14C]palmitate oxidation to 14CO2 was greater in those rats treated with ethanol instead of glucose. S-780 did not alter the oxidation rates over a 4 h period. Ethanol treatment increased the accumulation of [14C]palmitate in the PS + PI fraction of lung and decreased the proportion in PE. In kidney it increased the concentration of [14C]palmitate in TG, DG and PE and decreased the concentration in PC and PS + PI. Pretreatment of the rats with S-780 partially reversed the changes in palmitate accumulation in glycerolipids which were caused by ethanol. S-780 treatment also decreased the rate of hepatic TG synthesis from glycerol in the rats fed glucose. It increased the percentage recovery of [14C]palmitate in the livers and kidneys of glucose fed rats and decreased that in adipose tissue. This treatment decreased the proportion of [14C]palmitate recovered in the TG of the kidneys and lungs of these rats and increased the proportion in PI + PS. The results are discussed in relation to the mechanisms by which ethanol and S-780 are thought to interfere with glycerolipid synthesis.