Abstract 3733: Postprandial Free Fatty Acid Metabolism During Fenofibrate Treatment Predicts Postprandial Lipid And Lipoprotein Changes
Objective: To determine the effects of fenofibrate (160 mg/d) on fasting and postprandial non-esterified fatty acids (NEFA) and lipoproteins in subjects with hypertriglyceridemia and the metabolic syndrome.
Methods: Fifty-nine subjects with fasting hypertriglyceridemia (≥1.7 mmol/L and <6.9 mmol/L) and two or more of the Adult Treatment Panel III criteria of the metabolic syndrome were randomized to fenofibrate (160 mg/d) or placebo in a double-blind controlled clinical trial. A standardized fat load (50 g/m2) was given after a 12 h fast. Blood specimens were obtained at fasting and 3.5 h and 8 h after the test meal.
Results: After the test meal, postprandial (area under the curve) NEFA increased (mean ± SEM) by 11.2 ± 5.1% in the placebo group; in contrast NEFA decreased by 18.6 ± 3.8% in the fenofibrate group (P=0.0001). No differences in fasting NEFA were observed between groups (P=0.16). Fenofibrate reduced postprandial triglycerides (−45.4%, P<0.0001) and significantly decreased postprandial large (−40.8%, P<0.0001) and medium (−49.5%, p<0.0001) very low-density lipoprotein (VLDL) particles, as well as small LDL (−40.3%, P<0.0001) and total LDL particles (−19.0%, P<0.005). Reduction in NEFA (AUC) correlated with reductions in postprandial triglycerides (r=0.73, P<0.0001), non-HDL-C (r=0.67, P<0.0001) and with increases in HDL-C (r=0.38, P<0.01). The reduction in NEFA was more strongly correlated with decreased large VLDL (r=0.72, P<0.0001) than medium VLDL (r=0.34, P<0.02) or small VLDL particles (r=0.22, P<0.13). Postprandial reductions in NEFA were also correlated with lowering of small LDL (r=0.53, P<0.0001) and total LDL particles (r=0.60, P<0.0001).
Conclusions: Treatment with fenofibrate significantly decreases postprandial NEFA and the reductions in NEFA are highly correlated with reductions in triglycerides, non-HDL-C and an increase in HDL-C. Postprandial NEFA are an important predictor of postprandial lipoprotein changes in subjects with hypertriglyceridemia.