Factorial study of the effect of n-3 fatty acid supplementation and atorvastatin on the kinetics of HDL apolipoproteins A-I and A-II in men with abdominal obesity.

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Chan DC, Watts GF, Nguyen MN, Barrett PH

Factorial study of the effect of n-3 fatty acid supplementation and atorvastatin on the kinetics of HDL apolipoproteins A-I and A-II in men with abdominal obesity.

Am J Clin Nutr. 2006 Jul;84(1):37-43.

PubMed ID
16825679 [ View in PubMed
]
Abstract

BACKGROUND: Disturbed HDL metabolism in insulin-resistant, obese subjects may account for an increased risk of cardiovascular disease. Fish oils and atorvastatin increase plasma HDL cholesterol, but the underlying mechanisms responsible for this change are not fully understood. OBJECTIVE: We studied the independent and combined effects of fish oils and atorvastatin on the metabolism of HDL apolipoprotein A-I (apo A-I) and HDL apo A-II in obese men. DESIGN: We conducted a 6-wk randomized, placebo-controlled, 2 x 2 factorial intervention study of the effects of fish oils (4 g/d) and atorvastatin (40 mg/d) on the kinetics of HDL apo A-I and HDL apo A-II in 48 obese men with dyslipidemia with intravenous administration of [d3]-leucine. Isotopic enrichments of apo A-I and apo A-II were measured with gas chromatography-mass spectrometry with kinetic parameters derived from a multicompartmental model (SAAM II). RESULTS: Fish oils and atorvastatin significantly decreased plasma triacylglycerols and increased HDL cholesterol and HDL2 cholesterol (P < 0.05 for main effects). A significant (P < 0.02) main effect of fish oils was observed in decreasing the fractional catabolic rate of HDL apo A-I and HDL apo A-II. This was coupled with a significant decrease in the corresponding production rates, accounting for a lack of treatment effect on plasma concentrations of apo A-I and apo A-II. Atorvastatin did not significantly alter the concentrations or kinetic parameters of HDL apo A-I and HDL apo A-II. None of the treatments altered insulin resistance. CONCLUSIONS: Fish oils, but not atorvastatin, influence HDL metabolism chiefly by decreasing both the catabolism and production of HDL apo A-I and HDL apo A-II in insulin-resistant obese men. Addition of atorvastatin to treatment with fish oils had no additional effect on HDL kinetics compared with fish oils alone.

DrugBank Data that Cites this Article

Pharmaco-metabolomics
DrugDrug GroupsMetaboliteChangeDescription
AtorvastatinApprovedHDL2 cholesterol
increased
Atorvastatin increases the level of HDL2 cholesterol in the blood
Omega-3-acid ethyl estersApproved InvestigationalHDL2 cholesterol
increased
Omega-3-acid ethyl esters increases the level of HDL2 cholesterol in the blood
Omega-3-acid ethyl estersApproved InvestigationalTriglycerides
decreased
Omega-3-acid ethyl esters decreases the level of Triglycerides in the blood
AtorvastatinApprovedLathosterol
decreased
Atorvastatin decreases the level of Lathosterol in the blood
Omega-3-acid ethyl estersApproved InvestigationalHDL cholesterol
increased
Omega-3-acid ethyl esters increases the level of HDL cholesterol in the blood
AtorvastatinApprovedTotal cholesterol
decreased
Atorvastatin decreases the level of Total cholesterol in the blood
AtorvastatinApprovedTriglycerides
decreased
Atorvastatin decreases the level of Triglycerides in the blood
AtorvastatinApprovedLDL cholesterol
decreased
Atorvastatin decreases the level of LDL cholesterol in the blood
AtorvastatinApprovedHDL cholesterol
increased
Atorvastatin increases the level of HDL cholesterol in the blood