Inhibition of Apolipoprotein Secretion and Phosphatidate Phosphohydrolase Activity by Eicosapentaenoic and Docosahexaenoic Acids in the Perfused Rat Liver

Infusion of albumin-bound eicosapentaenoic acid (EPA) docosahexaenoic acid (DHA), or oleic acid (OA) in perfused rat livers was carried out for two hours at a rate that maintained the perfusate concentration at 1 mmol/L. When compared with fatty acid-poor albumin alone, triacylglycerol (TAG) output was not significantly increased with DHA or EPA, whereas OA infusion resulted in a twofold increase. Incorporation of labeled leucine into VLDL apo B-100, apo B-48, apo E, and apo Cs was decreased by 50% by DHA or EPA compared with OA. The total phosphatidate phosphohydrolase activity was decreased by 35% with DHA or EPA compared to oleic acid or albumin alone. In no case was there a significant change in the distribution of activity between the microsomal and cytosolic factions. Fatty acid infusion did not significantly change the liver TAG content. Total liver lipids, microsomal lipids, and lipids of secreted VLDL were enriched with the infused fatty acids. The degree of enrichment for secreted TAG averaged 24% for OA and 36% for DHA or EPA. The effects of DHA and EPA on PPH activity and on apo B secretion in feeding experiments with marine oils rich in these acids may relate to changes in the fatty acid composition of liver membranes.