Th-W56:2 Clinical studies on biomarkers

Abstract

The effect of a single oral fat meal (60 g fat/m2 body surface area) enriched in either saturated (SFA) or polyunsaturated ([PUFA] ω-6 or ω-3) fatty acids on postprandial lipoprotein levels was studied in four men with primary hypoalphalipoproteinemia (HP) and in four-age- and sex-matched controls. Vitamin A was included in the meal to label intestinally derived triglyceride-rich particles (TRP) with retinyl palmitate (RP). The HP subjects were either mildly hypertriglyceridemic (group A) or normotriglyceridemic (group B) and were phenotyped for post-heparin lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities and apolipoprotein (apo) E isoforms. Postprandial total plasma triglyceride (TG), high-density lipoprotein (HDL) cholesterol, and RP and TG concentrations in the chylomicron (Sf > 1,000) and nonchylomicron (Sf > 1,000) fractions were evaluated for 24 hours after the meal. At each time point, HDL composition and size and apolipoprotein distributions were also measured. Following the SFA meal, HP subjects had maximal plasma TG levels at 8 hours (4 hours in controls) with a slow return to baseline levels at 12 to 24 hours (8 to 12 hours for controls). In contrast, after the ω-6 meal plasma TG levels decreased in group A subjects, while group B subjects and controls showed only a small increase. The results after the ω-7 meal were intermediate between the SFA and the ω-3 meal. When compared with group B, subjects in group A showed higher levels of RP-associated TRP, slower clearance rates, 30% to 50% lower fasting LPL activity, and 1.5-fold to twofold higher fasting plasma apo C-III levels. The major preprandial HDL subclass in HP subjects was HDL3, which showed a relative decrease in cholesterol esters (CE) and an increase in TG levels following the SFA meal. After the ω-3 meal, HDL of group A subjects showed a decrease in TG, a reciprocal increase in CE, and either no changes or minor changes in phospholipid (PL) and free-cholesterol (FC) levels. The results show that HP subjects with mild preprandial hypertriglyceridemia respond to a single fat meal differently than subjects with normotriglyceridemia, and that this difference is the result of HP in addition to other factors such as low LPL and HTGL activities, high plasma apo C-III levels, and apo E2 phenotype.