Effect of fenofibrate and atorvastatin on VLDL apoE metabolism in men with the metabolic syndrome

Abstract

We examined the effects of fenofibrate and atorvastatin on very low density lipoprotein (VLDL) apolipoprotein (apo)E metabolism in the metabolic syndrome (MetS). We studied 11 MetS men in a randomized, double-blind, crossover trial. VLDL-apoE kinetics were examined using stable isotope methods and compartmental modeling. Compared with placebo, fenofibrate (200 mg/day) and atorvastatin (40 mg/day) decreased plasma apoE concentrations (P < 0.05). Fenofibrate decreased VLDL-apoE concentration and production rate (PR) and increased VLDL-apoE fractional catabolic rate (FCR) compared with placebo (P < 0.05). Compared with placebo, atorvastatin decreased VLDL-apoE concentration and increased VLDL-apoE FCR (P < 0.05). Fenofibrate and atorvastatin had comparable effects on VLDL-apoE concentration. The increase in VLDL-apoE FCR with fenofibrate was 22% less than that with atorvastatin (P < 0.01). With fenofibrate, the change in VLDL-apoE concentration was positively correlated with change in VLDL-apoB concentration, and negatively correlated with change in VLDL-apoB FCR. In MetS, fenofibrate and atorvastatin decreased plasma apoE concentrations. Fenofibrate decreased VLDL-apoE concentration by lowering VLDL-apoE production and increasing VLDL-apoE catabolism. By contrast, atorvastatin decreased VLDL-apoE concentration chiefly by increasing VLDL-apoE catabolism. Our study provides new insights into the mechanisms of action of two different lipid-lowering therapies on VLDL-apoE metabolism in MetS.

Fig. 1.

Compartment model describing apoE tracer kinetics. Leucine tracer is injected into plasma compartment 2 and distributes to extravascular compartments 1, 3, and 4. Compartments 1–4 are required to describe leucine tracer kinetics observed in plasma. Compartment 1 is connected to an intracellular delay compartment (compartment 5) that accounts for the time required for tissue assembly, synthesis, and secretion of apoE and/or apoE that was transported into VLDL indirectly from other lipoprotein fractions due to lipoprotein conversions or apolipoprotein exchange. Compartment 6 describes the kinetics of VLDL-apoE.