Phosphatidylinositol promotes cholesterol transport in vivo

Abstract

To examine the role that lipoprotein charge plays in cholesterol metabolism in vivo, we characterized the effects of an intravenous injection of 40 mol 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. -Stamler,

Dietary Phosphatidylinositol Prevents the Development of Nonalcoholic Fatty Liver Disease in Zucker (fa/fa) Rats

“…The relative liver weight was 21% less in PI-fed rats, and this was associated with a marked reduction (77%) in the triglyceride accumulation in the liver. Additionally, hepatic cholesterol level was markedly decreased (by 40%) in PI-fed rats (TG group, 99.7 ± 4.4 µmol/liver; PI group, 59.4 ± 1.4 µmol/liver, P < 0.05), a result that is in agreement with previous studies showing that PI administration promotes cholesterol transport and excretion in rabbits , . The extent and the direction (increase or decrease) of changes in liver lipoprotein synthesis and secretion during the development of NAFLD have been controversial , .…”

“…a Contained 7% soybean oil as dietary fat. b Contained 5% soybean oil + 2% soybean PI as dietary fats.Figure 1.rabbits(30,31). The extent and the direction (increase or decrease) of changes in liver lipoprotein synthesis and secretion during the development of NAFLD have been controversial (4, 5).…”

Molecular Characterization of Phospholipids by High-Performance Liquid Chromatography Combined with an Evaporative Light Scattering Detector, High-Performance Liquid Chromatography Combined with Mass Spectrometry, and Gas Chromatography Combined with a Flame Ionization Detector in Different Oat Varieties

“…With regard to PI, our results are higher than those reported using TLC, possibly because of an incomplete recovery from TLC. The high content of PI (about 20% of total phospholipid composition) is very interesting because several studies have shown that PI affects lipoprotein metabolism by controlling interactions and regulating signaling pathways. − In fact, it has been demonstrated that PI can act with increasing cholesterol excretion . Burgess et al determined the safety and therapeutic value, after oral administration, of PI in normolipidemic (normal levels of lipids) human subjects.…”

Plasma Phospholipidomic Profile Differs between Children with Phenylketonuria and Healthy Children

“…3 Regarding the increase of PI species, namely, PI (36:4) and PI (38:4), observed in PKU children, it is known that PI species influence the structure and function of plasma lipoproteins, but their role in plasma is unclear and requires further investigation. 73 Alterations in the PI content are probably associated with their signaling roles, as they are important precursors of signaling molecules, such as PIPs that regulate metabolic processes. 74 Therefore, we speculate that the observed increase in PI species could be associated with a decrease in its phosphorylation to phosphoinositides, by PI kinases (e.g.…”