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Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. In this study, postprandial changes in plasma lipids, high-density lipoprotein (HDL) composition and cholesteryl ester transfer protein (CETP) and lecithin: cholesterol acyltransferase (LCAT) activity levels were investigated in response to moderate alcohol consumption. A dose of 40 g of alcohol was consumed as beer, wine or spirits by eight healthy middle-aged men before and during dinner thus simulating social drinking. Lipid parameters were studied before, and at 1, 3, 5, 9, and 13 h after dinner. An alcohol-induced elevation of plasma triglycerides was observed at 3 and 5 h after dinner, but total plasma cholesterol and apolipoprotein B were hardly affected. HDL lipids changed during the postprandial phase after alcohol consumption, HDL triglycerides were elevated at 5 and 9 h, HDL phospholipids were elevated at 9 and 13 h, and HDL cholesterol was elevated at 13 h. A 6% increase in the concentration of apolipoprotein A-II was observed at 13 h. Plasma LCAT activity was slightly increased 9 h after dinner, but CETP activity levels were not affected. The LCAT changes appeared similar for all three alcoholic beverages. It is concluded that moderate alcohol consumption with dinner affects plasma triglyceride concentration as well as HDL composition.Chemicals/CAS: Apolipoproteins; Carrier Proteins; CETP protein, human; Cholesterol Ester Transfer Proteins; Cholesterol, 57-88-5; Cholesterol, HDL; Ethanol, 64-17-5; Glycoproteins; Phosphatidylcholine-Sterol O-Acyltransferase, EC 2.3.1.43; Phospholipids; Triglycerides

The present study examined the relative contributions of the different pathways by which oxidatively modified VLDL (oxVLDL) promotes the uptake and intracellular accumulation of lipids in J774 macrophages. VLDL was oxidized for a maximum of 4 hours, resulting in an increase in thiobarbituric acid- reactive substances and an increased electrophoretic mobility on agarose gel. The lipid composition of the relatively moderately oxidized VLDL samples did not differ significantly from that of nonoxidized VLDL samples. The uptake of J25I-labeled VLDL by the J774 cells increased with oxidation time and was completely blocked on coincubation with polyinosinic acid (PolyI), indicating that oxVLDL is taken up by the cells via the scavenger receptor only. Despite the 2-fold increased uptake of oxVLDL protein, the cell association of triglyceride (TG)-derived fatty acids by the J774 macrophages after incubation with oxVLDL was only 50% of that with native VLDL. In line with these observations, the induction of de novo synthesis of TG by J774 cells was ≃3-fold less efficient after incubation with oxVLDL than after incubation with native VLDL. The induction of de novo synthesis of TG with oxVLDL was even further decreased on simultaneous incubation with PolyI, whereas PolyI did not affect the native VLDL-induced TG synthesis. These results indicate that oxVLDL induces endogenous TG synthesis predominantly through particle uptake via the scavenger receptor and much less via the extracellular lipoprotein lipase (LPL)-mediated hydrolysis of TG, as is the case for native VLDL. In line with these observations, we showed that the suitability of VLDL as a substrate for LPL decreases with oxidation time. Addition of oxVLDL to the LPL assay did not interfere with the lipolysis of native VLDL. However, enrichment of the oxidized lipoprotein particle with native apoC2 was able to fully restore the impaired lipolysis. Thus, from these studies it can be concluded that on oxidation, VLDL becomes less efficient in inducing TG accumulation in J774 cells as a consequence of a defect in apoC2 as an activator for the LPL-mediated extracellular lipolysis.