Alterations in molecular species of cholesterol esters formed via plasma lecithin-cholesterol acyltransferase in human subjects consuming fish oil

Abstract

The influence of a dietary supplement of n-3 polyunsaturated fatty acids containing eicosapentaenoic acid (EPA, 20: 5n-3) and docosahexaenoic acid (DHA, 22:6n-3) on the molecular species of cholesteryl esters (CE) formed via the plasma lecithin (phosphatidylcholine) -cholesterol acyltransferase (LCAT; EC 2.3.1.43) reaction was evaluated. For this purpose, one group of eight subjects received an encapsulated fish lipid concentrate (MaxEPA) and another group of eight volunteers in the control group received encapsulated olive oil for 22 days. Plasma lipid profiles and fatty acid compositions of plasma phosphatidylcholine (PC) and CE were measured at day 0 and day 22 in all subjects. A decrease in plasma triglyceride (by 34%) and a moderate rise in high-density lipoprotein (HDL)-cholesterol (by 13%) was observed in the MaxEPA group. For characterization of the plasma LCAT-derived reaction products formed in vitro, [ 14 C]cholesterol was used as the substrate and the newly formed molecular species of [ 14C]CE were separated by argentation thin-layer chromatography. Marked shifts were found in the abundance of the various classes of LCAT-derived products in the MaxEPA group whereas no significant changes were observed in the controls. The proportion of the [ 14C]CE as pentaenoic (EPA) species rose by 9-fold (from 1.5% at day 0 to 14.4% at day 22) as the dienoic (linoleate) species fell (from 50.6 to 39.2%); a moderate rise in the hexaenoic (DHA) species (from 1.7 to 2.4%) with no significant change in the tetraenoic (arachidonate) (AA) species was observed. The LCAT results were in the order of the observed shifts in the fatty acid patterns of the plasma CE. The relative formation of different molecular species of [ 14C]CE via the plasma LCAT reaction as measured in vitro in the MaxEPA consumers was significantly different from the relative mol% distributions of the corresponding polyunsaturated fatty acids in plasma PC thereby suggesting the relative order of participation in the LCAT reaction in the MaxEPA group to be EPA > AA > DHA. The potential physiological significance of these findings is discussed in relation to EPA/DHA and HDL-cholesterol metabolism and function including cellular eicosanoid synthesis.