Phosphatidylinositol promotes cholesterol transport in vivo

To examine the role that lipoprotein charge plays in cholesterol metabolism in vivo, we characterized the effects of an intravenous injection of 40 micromol of an uncharged phospholipid (phosphatidylcholine, PC) or an anionic phospholipid (phosphatidylinositol, PI) into fasted rabbits. PC injection had a negligible effect on lipoprotein charge and composition, similar to that observed in a saline-injected animal. In contrast, PI injection caused a significant increase in the net negative surface charge of all lipoproteins after only 10 min, followed by a gradual return to normal by 24 h. Lipoprotein compositional analysis showed that PI caused a significant increase of cholesteryl ester (CE) and cholesterol (FC) in the VLDL pool by 3 h, with no changes in VLDL-triglyceride content. While the bulk of the plasma CE was located in the HDL pool in the PC-injected animals, in the PI animals, VLDL became the major CE storage compartment. No major changes in the levels or composition of HDL or LDL were evident over the 24-h turnover period. Co-injection of [(3)H]FC revealed a 30-fold greater rate of clearance of the labeled cholesterol from the PI-injected rabbit plasma. In addition, the rate of cholesterol esterification by lecithin:cholesterol acyltransferase was almost completely inhibited in the PI animals. In summary, a bolus injection of PI into rabbits appears to enhance the mobilization of cellular sterol and promote a rapid clearance of both FC and CE from the plasma compartment. The data show that lipoprotein charge can affect cholesterol transport and that this process can be selectively manipulated.