(10-04-10) Effects of atorvastatin and n?3 fatty acid supplementation on VLDL apolipoprotein C-III kinetics in men with abdominal obesity1,2,3

Dick C Chan, Minh N Nguyen, Gerald F Watts, Esther MM Ooi and P Hugh R Barrett

1 From the Metabolic Research Centre School of MedicinePharmacology Royal Perth Hospital University of Western Australia Perth Western Australia.
2 Supported by a project grant from the National Health and Medical Research Foundation (NHMRC) of Australia. DCC is an NHMRC Career Development Fellow. EMMO is a fellow of the National Heart Foundation of Australia. PHRB is an NHMRC research fellow. The fish-oil and corn oil capsules were a generous gift from Pronova Biocare, Oslo, Norway.
3 Address correspondence to PHR Barrett, School of Medicine and Pharmacology, University of Western Australia, Royal Perth Hospital, GPO Box X2213, Perth, Western Australia, WA 6847. E-mail: [email protected] .
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.
Design: 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 D3-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.

Source: Am J Clin Nutr 91: 900-906, 2010

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