EFFECTS OF OMEGA-3-FATTY-ACIDS ON INTRAVASCULAR LIPOLYSIS OF VERY-LOW-DENSITY LIPOPROTEINS IN HUMANS

Very-low-density lipoproteins (VLDLs) are the major carriers of fastin g plasma triglyceride (TG). TG-enriched VLDLs become cholesterol (C)-e nriched low-density lipoproteins (LDLs) through hydrolysis facilitated by lipoprotein lipase (LPL). Omega-3 fatty acid (n-3 FA) supplementat ion may increase LDL-C while decreasing plasma TG in hypertriglyceride mic patients. It has been proposed that n-3 FAs increase LDL C by prom oting production of TG-poor VLDL and accelerating conversion of VLDL t o LDL. To study the effects of n-3 FA supplementation on in vivo lipol ysis of VLDL directly, we treated 11 hypertriglyceridemic subjects wit h n-3 FA (3.3 g/d). Each participant was studied three times: at basel ine, after a 1-month period of run-in olive oil placebo, and after 1 m ore month of n-3 FA supplementation. Lipolysis was induced by intraven ous infusion of heparin for 2 hours. Plasma samples were obtained ever y 30 minutes for determination of lipids and apoproteins (apos), separ ation of individual lipoproteins by fast protein liquid chromatography (FPLC), and measurement of LPL and hepatic TG lipase (HTGL) levels. n -3 FA supplementation decreased fasting plasma TG (2.51 +/- 0.23 v 3.9 7 +/- 0.46 mmol/L), VLDL-TG (1.08 +/- 0.18 v 2.35 +/- 0.35 mmol/L), an d VLDL-C (0.39 +/- 0.05 v 0.72 +/- 0.13 mmol/L) while increasing LDL-C (3.59 +/- 0.21 v 3.00 +/- 0.23 mmol/L) and plasma apo B (3.31 +/- 0.1 9 v 2.90 rt 0.17 mmol/L). The absolute rate of TG lipolysis correlated with fasting TG (r = .74, P < .005) and was lower after n-3 FA supple mentation (0.11 +/- 0.01 mmol/mL/min) as compared with placebo (0.19 /- 0.01, P < .01), whereas percent decreases from baseline TG levels w ere similar at entry onto the study (57.4% +/- 2.5%), after placebo (5 8.8% +/- 2.7%), and after n-3 FA(52% +/- 3.6%). During lipolysis, LDL- C increased in correlation with the decrease in VLDL-C (r = -.41, P < .03), consistent with the product-precursor relationship. Postheparin LPL activity at 2 hours correlated inversely with fasting TG (r = -.53 , P < .05), but not with either the decreases in VLDL-TG and VLDL C or the increase in LDL-C. These data demonstrate that n-3 FA supplementa tion does not accelerate lipolysis of VLDL and even decreases the VLDL -C pool, which is the precursor of LDL-C. Therefore, the increase seen in fasting LDL-C is probably mediated through mechanisms other than a cceleration of VLDL lipolysis. Copyright (C) 1995 by W.B. Saunders Com pany