title: 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.
authors.affiliation: Metabolic Research Centre, School of Medicine and Pharmacology,  University of Western Australia, Perth, Western Australia,  Australia.
authors.forename: Esther M M
authors.initials: EM
authors.lastname: Ooi
authors.forename: Theodore W K
authors.initials: TW
authors.lastname: Ng
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.forename: Dick C
authors.initials: DC
authors.lastname: Chan
authors.forename: P Hugh R
authors.initials: PH
authors.lastname: Barrett
mesh_terms: D000328:Adult; D001055:Apolipoproteins B / Q000097:blood / Q000378:metabolism; D001057:Apolipoproteins E / Q000097:blood / Q000378:metabolism*; D000069059:Atorvastatin; D004311:Double-Blind Method; D011345:Fenofibrate / Q000627:therapeutic use*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*
chemical_list: D001055:Apolipoproteins B; D001057:Apolipoproteins E; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008079:Lipoproteins, VLDL; D011758:Pyrroles; D000069059:Atorvastatin; D011345:Fenofibrate