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

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.