This article is available online at http://www.jlr.org Health consequences associated with low intakes of the long-chain, marine omega-3 (n3) FAs have become a central issue in nutritional lipid research. The United States Department of Agriculture's 2010 Dietary Guidelines recommend consumption of 8 ounces per week of fi sh, providing an average of 250 mg eicosapentaenoic acid (20:5n3) and docosahexaenoic acid (22:6n3) per day for prevention of heart disease ( 1 ). Moreover, public awareness regarding the potential health benefi ts of n3 FAs has spurred an increase in fatty fi sh and fi sh oil consumption ( 2 ).Although the mechanisms by which n3-HUFAs improve health are still being explored, it is clear that increasing n3-HUFA intake can decrease the risk of cardiovascular disease (CVD) in at-risk individuals ( 3-5 ). In hyperlipidemic subjects, treatment with high doses of n3-HUFAs lowers triglycerides ( 6 ) and improves total:HDL cholesterol ratios ( 6, 7 ), a surrogate marker associated with a reduction in CVD risk. The n3-HUFAs 20:5n3 and 22:6n3 also reduce infl ammatory responses in a range of conditions ( 8-10 ). A well-accepted effect of n3-HUFA supplementation is a reduction in thrombin-stimulated platelet aggregation due to decreased platelet cyclooxygenase metabolism ( 11 ). More recently, a cyclooxygenase-independent diminution of platelet sensitivity to collagen has been reported after P-OM3 treatment ( 12 ). Thus, an increase in the anti-infl ammatory n3-HUFAs, which lowers the more proinfl ammatory n6-HUFAs ( 13-15 ), at least partially explains the health benefi ts of n3-HUFA consumption ( 8-10 ). 5306-51530-019-00D (J.W.N.), National Institute of Food and Agriculture National Needs Fellowship grant 2008-38420-04759 (A.H.K.), and by grant LVZ112860 from GlaxoSmithKline (G.C.S.) Abbreviations: CVD, cardiovascular disease; HUFA, highly unsaturated fatty acid; P-OM3, prescription omega-3 acid ethyl esters; RBC, red blood cell.

ObjectiveThe purpose of this study was to compare the apolipoprotein composition of the three major lipoprotein classes in patients with metabolic syndrome to healthy controls.MethodsVery low density (VLDL), intermediate/low density (IDL/LDL, hereafter LDL), and high density lipoproteins (HDL) fractions were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex matched healthy volunteers. The apolipoprotein content of fractions was analyzed by one-dimensional (1D) gel electrophoresis with confirmation by a combination of mass spectrometry and biochemical assays.ResultsMetabolic syndrome patients differed from healthy controls in the following ways: (1) total plasma - apoA1 was lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2) VLDL - apoB, apoC3, and apoE were increased; (3) LDL - apoC3 was increased, (4) HDL -associated constitutive serum amyloid A protein (SAA4) was reduced (p<0.05 vs. controls for all). In patients with metabolic syndrome, the most extensively glycosylated (di-sialylated) isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%, 30%, and 25%, respectively (p<0.01 vs. controls for all). Similarly, the glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%, 26%, and 37% (p<0.01 vs. controls for all). Finally, glycosylated isoform of SAA4 in HDL fraction was 42% lower in patients with metabolic syndrome compared with controls (p<0.001).ConclusionsPatients with metabolic syndrome displayed several changes in plasma apolipoprotein composition consistent with hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of which remain to be determined.

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