Randomized controlled trial of the effect of n-3 fatty acid supplementation on the metabolism of apolipoprotein B-100 and chylomicron remnants in men with visceral obesity

Background: Lipid abnormalities may contribute to the increased risk of atherosclerosis and coronary disease in visceral obesity. Fish oils lower plasma triacylglycerols, but the underlying mechanisms are not fully understood. Objective: We studied the effect of fish oils on the metabolism of apolipoprotein B-100 (apo B) and chylomicron remnants in obese men. Design: Twenty-four dyslipidemic, viscerally obese men were randomly assigned to receive either fish oil capsules (4 g/d, consisting of 45% eicosapentaenoic acid and 39% docosahexaenoic acid as ethyl esters) or matching placebo (corn oil, 4 g/d) for 6 wk. VLDL, intermediate-density lipoprotein (IDL), and LDL apo B kinetics were assessed by following apo B isotopic enrichment with the use of gas chromatography-mass spectrometry after an intravenous bolus injection of trideuterated leucine. Chylomicron remnant catabolism was measured with the use of an intravenous injection of a chylomicron remnant like emulsion containing cholesteryl [C-13]oleate, and isotopic enrichment of (CO2)-C-13 in breath was measured with isotope ratio mass spectrometry. Kinetic values were derived with multicompartmental models. Results: Fish oil supplementation significantly (P < 0.05) lowered plasma concentrations of triacylglycerols (-18%) and VLDL ape B (-20%) and the hepatic secretion of VLDL ape B (-29%) compared with placebo. The percentage of conversions of VLDL ape B to IDL ape B, VLDL ape B to LDL ape B, and IDL ape B to LDL ape B also increased significantly (P < 0.05): 71%, 93%, and 11%, respectively. Fish oils did not significantly alter the fractional catabolic rates of ape B in VLDL, IDL, or LDL or alter the catabolism of the chylomicron remnant-like emulsion. Conclusion: Fish oils effectively lower the plasma concentration of triacylglycerols, chiefly by decreasing VLDL ape B production but not by altering the catabolism of ape B-containing lipoprotein or chylomicron remnants.