Suppression of Rat Liver Fatty Acid Synthesis by Eicosa-5,8,11,14-tetraynoic Acid without a Reduction in Lipogenic Enzymes

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Abstract
In meal-fed rats supplementation of safflower oil (5 g per 100 g diet) to a fat-free basal diet resulted in the characteristic suppression of liver fatty acid synthetase and acetyl-CoA carboxylase activities, which was accompanied by a 60% decrease in the rate of hepatic fatty acid synthesis. The decline in activity of these lipogenic enzymes was completely prevented by adding 0.05% eicosa-5,8,11,14-tetraynoic acid (TYA) to the safflower oil diet. Fatty acid analysis of the livers indicated that TYA significantly impaired the conversion of linoleate to arachidonate. Apparently the selective suppression of lipogenic enzymes by dietary linoleate is not caused by linoleate per se but requires its conversion to longer-chain fatty acids and/or prostaglandins. In spite of high activities of fatty acid synthetase and acetyl-CoA carboxylase, liver fatty acid synthesis continued to be inhibited by the safflower oil + TYA dietary regimen. This continued inhibition of lipogenesis was due to the TYA, because addition of TYA to the fat-free diet precipitated a significant decline in liver fatty acid synthesis without a drop in lipogenic enzymes. Inhibition of fatty acid synthesis by TYA could not be attributed to a decrease in liver glucose utilization based on hepatic glycogen concentration, nor was it due to a reduction in the fraction of catalytically active polymeric acetyl-CoA carboxylase based on sensitivity of the enzyme activity to avidin.