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 moiet ies in the plasma. In this study, using oleate and human umbilical vei n endothelial cells, we asked whether the vehicle that delivers fatty acid to cells has an influence on its metabolism upon its incorporatio n into the cell. For oleate vehicles, we compared free oleate bound to albumin with oleate in low density lipoprotein (LDL) which was delipi dated and reconstituted with either radiolabeled triolein or cholester yl oleate. Using approximately physiologic concentrations of LDL and f ree 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 o leate delivered as free oleate bound to albumin. In fact, the differen ce was most marked between cholesteryl oleate and triolein, even thoug h the oleate in cholesteryl oleate and triolein was delivered in ident ically 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 i n reconstituted LDL was desaturated and elongated to fatty acid metabo lites, but cholesteryl oleate in reconstituted LDL was not similarly m etabolized. The elongated and desaturated metabolites of oleate were p referentially esterified in cellular triglyceride when oleate was deli vered as free oleate, but they were preferentially esterified in phosp holipids when oleate was delivered as triolein in LDL. Second, we obse rved that there was a difference in the distribution of oleate among p hospholipids when oleate was delivered as cholesteryl oleate in recons tituted LDL versus triolein in reconstituted LDL. When the oleate was delivered as triolein in reconstituted LDL, there was greater esterifi cation in diacyl phosphatidylethanolamine, in phosphatidylserine, and in phosphalidylinositol. When oleate was delivered as cholesteryl olea te in reconstituted LDL, there was greater esterification in diacyl ph osphatidylcholine. Third, there was a marked preference for oleate del ivered from triolein in LDL over cholesteryl oleate in LDL for esterif ication into the sn-1 position of plasmalogens as a vinyl ether-linked fatty acid. These data indi cate 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.