Mode of transport of fatty acid to endothelial cells influences intracellular fatty acid metabolism

Fatty acids are transported to cells from a variety of different moieties in the plasma. In this study, using oleate and human umbilical vein endothelial cells, we asked whether the vehicle that delivers fatty acid to cells has an influence on its metabolism upon its incorporation into the cell. For oleate vehicles, we compared free oleate bound to albumin with oleate in low density lipoprotein (LDL) which was delipidated and reconstituted with either radiolabeled triolein or cholesteryl oleate. Using approximately physiologic concentrations of LDL and free oleate, we demonstrated by three lines of evidence unique patterns of cellular oleate metabolism for oleate delivered as triolein within LDL for oleate delivered as cholesteryl oleate within LDL, and for oleate delivered as free oleate bound to albumin. In fact, the difference was most marked between cholesteryl oleate and triolein, even though the oleate in cholesteryl oleate and triolein was delivered in identically reconstituted LDL particles, which were presumably incorporated into the cells and degraded in lysosomes in a similar fashion. First, we demonstrated that oleate delivered as free oleate or as triolein in reconstituted LDL was desaturated and elongated to fatty acid metabolites, but cholesteryl oleate in reconstituted LDL was not similarly metabolized. The elongated and desaturated metabolites of oleate were preferentially esterified in cellular triglyceride when oleate was delivered as free oleate, but they were preferentially esterified in phospholipids when oleate was delivered as triolein in LDL. Second, we observed that there was a difference in the distribution of oleate among phospholipids when oleate was delivered as cholesteryl oleate in reconstituted LDL versus triolein in reconstituted LDL. When the oleate was delivered as triolein in reconstituted LDL, there was greater esterification in diacyl phosphatidylethanolamine, in phosphatidylserine, and in phosphatidylinositol. When oleate was delivered as cholesteryl oleate in reconstituted LDL, there was greater esterification in diacyl phosphatidylcholine. Third, there was a marked preference for oleate delivered from triolein in LDL over cholesteryl oleate in LDL for esterification into the sn-1 position of plasmalogens as a vinyl ether- linked fatty acids. These data indicate that mode of transport of fatty acid to cells influences fatty acid metabolism upon its incorporation into the cell, even when the fatty acid is delivered from the core of the same lipoprotein.