Oxidized lipids in the diet are incorporated by the liver into very low density lipoprotein in rats

Abstract

Previous studies have shown that the quantity of oxidized lipids in the diet directly correlates with the level of oxidized chylomicrons in mesenteric lymph and the level of oxidized lipids in endogenous lipoproteins such as very low density lipoprotein (VLDL) and low density lipoprotein (LDL). The aim of the present study was to determine whether oxidized fatty acids in the diet are delivered via chylomicrons to the liver and whether these lipids are repackaged and secreted in VLDL. In these experiments, oxidized [14C]linoleic acid was utilized as a marker for oxidized dietary fats. When we determined the metabolism of nonoxidized and oxidized [14C]linoleic acid-labeled chylomicrons, we found that hepatic uptake was similar with 13.57 +/- 0.84% of nonoxidized and 13.40 +/- 0.96% of oxidized linoleic acid delivered to the liver 30 min after chylomicron administration. Additionally, uptake by the extrahepatic tissues was also similar. When the hepatic secretion of VLDL was determined in an in vitro perfusion system after the administration of nonoxidized and oxidized linoleic acid-labeled chylomicrons to intact animals, we found that oxidized linoleic acid was utilized for the formation and secretion of VLDL. After the administration of labeled nonoxidized and oxidized linoleic acid, 0.86 +/- 0.07% and 0.70 +/- 0.09% of the administered label was found in the liver perfusate at 2 h, respectively. The presence of oxidized linoleic acid in oxidized VLDL was confirmed by demonstrating the presence of hydroperoxide-derived hydroxy octadecanoic acid. Thus, our findings demonstrate that oxidized dietary lipids are delivered to the liver via chylomicrons where they are utilized for synthesis of endogenous lipoproteins such as VLDL.