Correlation of serum triglyceride and its reduction by omega-3 fatty acidswith lipid transfer activity and the neutral lipid compositions of high-density and low-density lipoproteins

Serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) co ncentrations are inversely correlated and mechanistically linked by means o f lipid transfer activities. Phospholipid transfer activity (PLTA) moves ph ospholipids among serum lipoproteins; cholesteryl ester transfer activity ( CETA), which exchanges cholesteryl esters (CE) and TG among lipoproteins, i s stimulated by nonesterified fatty acids (NEFA). The aims of this study we re (a) to develop a quantitative model that correlates the neutral lipid (N L = CE + TG) compositions of HDL and LDL with serum TG concentration; (b) i dentify the serum lipid determinants of CETA and PLTA, and; (c) identify th e effects of serum TC reductions on the neutral lipid compositions of HDL a nd LDL, serum NEFA concentrations, and on PLTA and CETA. These aims were ad dressed in 40 hypertriglyceridemic subjects before and after treatment with an 85% concentrate of omega-3 fatty acids (Omacor(TM)) and in 16 untreated normolipidemic subjects. In vivo, the NL compositions of LDL and HDL were described by a mathematical model having the form of adsorption isotherms: HDL - (TG/NL) = (0.90 +/- 0.07) serum TG/(7.0 +/- 1.2 mmol/l + serum TG) an d LDL - (TG/NL) = (0.65 +/- 0.08) serum TG/(4.9 +/- 1.5 mmol/l + serum TG). Reduction of serum TG was associated with reductions in HDL - (TG/NL), ser um NEFA concentration, and serum CETA but not PLTA. These data suggest that both hypertriglyceridemia and the attendant elevated serum CETA but not PL TA are determinants of HDL and LDL composition and structure and that serum TC concentrations are good predictors of the NL compositions of HDL and LD L. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.