Lack of triglyceride-lowering properties of fish oil in apolipoprotein E-deficient mice

Fish oil is a potent triglyceride (TG)-lowering agent in humans. The goal o f the present study was to assess the contribution of decreased triglycerid e 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/w t) for 2 weeks. Compared with coconut oil and sunflower oil, fish oil reduc ed the concentrations of cholesterol and triglycerides in the wild-type mic e, whereas it had no effect on cholesterol concentration and it had a trigl yceride-raising effect in apoE-deficient mice. The latter was due to increa sed triglyceride concentrations in the d<1.019 g/mL plasma density fraction . In apoE-deficient mice, but not in wild-type mice, the postprandial trigl yceride 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 t riglyceride metabolism in the fish oil-fed apoE-deficient mice. Compared wi th 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 lipase-mediated lipolysis of VLDL was lowered in the fish oil-fed wild-type and apoE-defic ient mice, suggesting an alteration in VLDL lipolysis independent of the mi ce genotype. In conclusion, fish oil does not decrease triglyceride concent rations in apoE-deficient mice despite reducing triglyceride production rat es, suggesting that decreased triglyceride synthesis is not sufficient to l ower 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.