Effect of n-3 fatty acids on the composition and binding properties of lipoproteins in hypertriglyceridemic patients

Abstract

Background: Treatment of hyperlipidemic patients with fish oil results in an increase in plasma LDL cholesterol despite a marked decrease in the LDL precursor, VLDL. Objective: We studied the relation between VLDL composition and LDL concentrations. Design: Fourteen hypertriglyceridemic patients were treated with encapsulated fish oil (containing 1.45 g eicosapentaenoic acid and 1.55 g docosahexaenoic acid/d) for 4 wk. Venous blood samples were collected before and after treatment. Eleven normolipidemic subjects served as a control group. Results: Fish oil effectively lowered plasma lipid and apolipoprotein (apo) E concentrations in the hypertriglyceridemic patients, whereas apo B concentrations increased. The lipid and apolipoprotein content of VLDL decreased, whereas LDL cholesterol and LDL apo B increased. Fractionation of VLDL by heparin-affinity chromatography showed that before treatment hypertriglyceridemic patients had more VLDL in the 0.05-mol NaCl/L subfraction and less in the 0.20-mol/L subfraction than did control subjects (P < 0.05), whereas the subfraction distribution pattern was normalized after fish-oil treatment. Nevertheless, plasma concentrations of the 0.05-mol NaCl/L subfraction were decreased and those of the 0.20-mol/L subfraction were increased in hypertriglyceridemic patients after fish-oil treatment (P < 0.05). Fish-oil treatment both enhanced VLDL binding and lowered LDL binding to fibroblasts. Conclusion: Treatment of hypertriglyceridemic patients with fish oil caused differential effects on VLDL subfractions and decreased LDL binding to fibroblast receptors, which may have contributed to the paradoxical increase in LDL-cholesterol concentrations.