Effects of atorvastatin and n-3 fatty acid supplementation on VLDL apolipoprotein C-III kinetics in men with abdominal obesity.
BACKGROUND
Disturbed apolipoprotein (apo) C-III metabolism in obese subjects may account for hypertriglyceridemia and increased risk of cardiovascular disease. Atorvastatin and fish oils decrease plasma triglycerides and VLDL concentrations, but the underlying mechanisms are not fully understood.


OBJECTIVE
We studied the independent and combined effects of atorvastatin and fish oils on the metabolism of VLDL apo C-III in obese men.


METHODS
We carried out a 6-wk randomized, placebo-controlled, 2 x 2 factorial intervention study of atorvastatin (40 mg/d) and fish oils (4 g/d) on VLDL apo C-III kinetics in the postabsorptive state in 39 abdominally obese men using intravenous administration of d(3)-leucine. VLDL apo C-III isotopic enrichments were measured by using gas chromatography-mass spectrometry with kinetic parameters derived by using a multicompartmental model.


RESULTS
Atorvastatin significantly (P < 0.05, main effect) increased the VLDL apo C-III fractional catabolic rate (+0.06 +/- 0.003 pools/d) without significantly altering its production rate (-0.14 +/- 0.18 mg . kg(-1) . d(-1)), accounting for a significant reduction in plasma VLDL apo C-III pool size (-44 +/- 17 mg/L). Fish-oil supplementation significantly decreased plasma triglycerides but did not significantly alter plasma VLDL apo C-III concentrations or kinetic parameters. Combination treatment provided no additional effect on VLDL apo C-III concentrations or kinetics compared with atorvastatin alone.


CONCLUSIONS
In obesity, the triglyceride-lowering effect of atorvastatin, but not fish oils, is associated with increased VLDL apo C-III fractional catabolism and hence lower VLDL apo C-III concentrations. Combination treatment provided no significant additional improvement in VLDL apo C-III metabolism compared with atorvastatin alone.
Chan
Dick C
DC
Metabolic Research Centre School of MedicinePharmacology Royal Perth Hospital University of Western Australia Perth Western Australia.
Nguyen
Minh N
MN
Watts
Gerald F
GF
Ooi
Esther Mm
EM
Barrett
P Hugh R
PH
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D053305:Apolipoprotein C-III / Q000097:blood / Q000378:metabolism*; D000069059:Atorvastatin; D015243:Cholesterol, VLDL / Q000097:blood*; D019587:Dietary Supplements; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology* / Q000627:therapeutic use; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000097:blood / Q000188:drug therapy*; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood*
D000924:Anticholesteremic Agents; D053305:Apolipoprotein C-III; D015243:Cholesterol, VLDL; D015525:Fatty Acids, Omega-3; D006538:Heptanoic Acids; D011758:Pyrroles; D014280:Triglycerides; D000069059:Atorvastatin