Atorvastatin and fenofibrate have comparable effects on VLDL-apolipoprotein C-III kinetics in men with the metabolic syndrome.
OBJECTIVE
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.


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.
Chan
Dick C
DC
Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
Watts
Gerald F
GF
Ooi
Esther M M
EM
Ji
Juying
J
Johnson
Anthony G
AG
Barrett
P Hugh R
PH
D000328:Adult; D053305:Apolipoprotein C-III / Q000097:blood*; D001054:Apolipoproteins A / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015536:Down-Regulation; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy*; D011345:Fenofibrate / Q000627:therapeutic use*; D008401:Gas Chromatography-Mass Spectrometry; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007700:Kinetics; D008079:Lipoproteins, VLDL / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy*; D008875:Middle Aged; D008954:Models, Biological; D011758:Pyrroles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D001055:Apolipoproteins B; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008079:Lipoproteins, VLDL; D011758:Pyrroles; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin; D011345:Fenofibrate