Objectives -The metabolic syndrome (MetS) is characterized by insulin resistance and dyslipidemia that may accelerate atherosclerosis. Disturbed apolipoprotein (apo) C-III metabolism may account for dyslipidemia in these subjects. Atorvastatin and fenofibrate decrease plasma apoC-III, but the underlying mechanisms are not fully understood.Methods and Results -The effects of atorvastatin (40 mg/d) and fenofibrate (200 mg/d) on the kinetics of very-low density lipoprotein (VLDL)-apoC-III were investigated in a crossover trial of 11 MetS men. VLDL -apoC-III kinetics were studied, after intravenous d(3)-leucine administration using gas chromatography-mass spectrometry and compartmental modeling. Compared with placebo, both atorvastatin and fenofibrate significantly decreased (P < 0.001) plasma concentrations of triglyceride, apoB, apoB-48, and total apoC-III. Atorvastatin, not fenofibrate, significantly decreased plasma apoA-V concentrations (P < 0.05). Both agents significantly increased the fractional catabolic rate (+ 32% and + 30%, respectively) and reduced the production rate of VLDL -apoC-III (-20% and -24%, respectively), accounting for a significant reduction in VLDL -apoC-III concentrations (-41% and -39%, respectively). Total plasma apoC-III production rates were not significantly altered by the 2 agents. Neither treatment altered insulin resistance and body weight.Conclusions -Both atorvastatin and fenofibrate have dual regulatory effects on VLDL -apoC-III kinetics in MetS; reduced production and increased fractional catabolism of VLDL -apoC-III may explain the triglyceride-lowering effect of these agents.
|Journal||Arteriosclerosis, thrombosis, and vascular biology|
|Publication status||Published - 2008|