Ethanol administration and the relationship of malonyl-coenzyme A concentrations to the rate of fatty acid synthesis in rat liver

Abstract

1. The effect of ethanol on liver fatty acid synthesis was studied in vivo in 24h-starved and ‘meal-fed’ rats (i.e. fed for 3h per day and not ad libitum). 2. In the fed animal³H₂O was incorporated into fat at a rate of 0.46μmol of C₂ units/min per g wet wt. of liver. Administration of either ethanol (3.2g/kg) or equicaloric amounts of glucose had no effect on the rate of³H₂O incorporation into lipid. 3. In the 24h-starved animal, administration of the same dose of ethanol produced an increase in the rate of³H₂O incorporation from 0.06 to 0.12μmol of C₂ units/min per g fresh wt. after 3h whereas [malonyl-CoA] increased from 0.006 to 0.009μmol/g. Glucose given in amounts equicaloric to ethanol was significantly more lipogenic, increasing both the³H₂O incorporation from 0.06 to 0.20μmol of C₂ units/min per g and the malonyl-CoA content from 0.006 to 0.013 μmol/g wet wt. at 3h. 4. The decrease in the redox state of free cytoplasm NAD or NADP couples or the changes in content of citrate, glucose 6-phosphate and pyruvate of liver after ethanol administration had no measurable effect on the rate of fatty acid synthesis in vivo. 5. Under the conditions of the experiments there was no significant difference, among any of the groups, in the activity of liver fatty acid synthetase measured in vitro. A double-reciprocal plot of the rate of³H₂O incorporation and the total tissue malonyl-CoA concentrations showed a striking relationship. It has been concluded that the rate of fatty acid synthesis in vivo is determined principally by the V_max. of fatty acid synthetase and the concentration of free malonyl-CoA. 6. It has also been concluded that under the conditions of the present study, the synthesis of fatty acids de novo is unlikely to be an important factor in the increased liver lipid content associated with ethanol administration.