Atherosclerosis and Lipoproteins |
From INSERM U-325 (G.A., E.B., J.C.F.) and INSERM U-508 (J.D.), Lille, France; and Département dAthérosclérose (G.A., E.B., J.C.F., J.D.), Institut Pasteur de Lille, Lille, France.
Correspondence to Dr Jean Dallongeville, Département dAthérosclérose, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59019 Lille Cedex, France. E-mail jean.dallongeville{at}pasteur-lille.fr
AbstractFish oil is a potent triglyceride (TG)-lowering agent in humans. The goal of the present study was to assess the contribution of decreased triglyceride synthesis and of apoE in mediation of the triglyceride-lowering effect of fish oil. To this end, apoE-deficient mice and wild-type control mice were supplemented with either coconut oil, sunflower oil, or fish oil (20% wt/wt) for 2 weeks. Compared with coconut oil and sunflower oil, fish oil reduced the concentrations of cholesterol and triglycerides in the wild-type mice, whereas it had no effect on cholesterol concentration and it had a triglycerideraising effect in apoE-deficient mice. The latter was due to increased triglyceride concentrations in the d<1.019 g/mL plasma density fraction. In apoE-deficient mice, but not in wild-type mice, the postprandial triglyceride area under the curve was higher after an intragastric load of fish oil than after a sunflower oil load. These data indicate an impairment of triglyceride metabolism in the fish oilfed apoE-deficient mice. Compared with coconut oil and sunflower oil, fish oil lowered triglyceride production rates measured with the Triton method in both wild-type (P<0.0001) and apoE-deficient mice (P<0.0001). Similarly, in vitro lipoprotein lipasemediated lipolysis of VLDL was lowered in the fish oilfed wild-type and apoE-deficient mice, suggesting an alteration in VLDL lipolysis independent of the mice genotype. In conclusion, fish oil does not decrease triglyceride concentrations in apoE-deficient mice despite reducing triglyceride production rates, suggesting that decreased triglyceride synthesis is not sufficient to lower triglyceride concentrations in mice. ApoE appears to be necessary for fish oil to lower plasma triglyceride concentrations, indicating a critical role of apoE in this process.
Key Words: apolipoprotein E triglycerides fish oil diet lipoprotein VLDL lipoprotein lipase atherosclerosis nutrition
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