Interaction of fenofibrate and fish oil in relation to lipid metabolism in mice.

Aim: The aim of our study is to elucidate the interactive effects on lipid metabolism of fenofibrate and two fish oils with EPA and DHA contents in mice.

Methods: Female C57BL/6J mice were fed purified experimental diets containing safflower oil (SO), EPA-rich menhaden oil (MO) or DHA-rich tuna oil (TO) with or without 0.1% fenofibrate for 8 weeks. At the end of the experiments, we measured plasma lipids and hepatic triglycerides and cholesterol, and the hepatic mRNA expression of lipogenic and lipidolytic genes.

Results: Plasma TG levels fell in the group fed MO or TO alone and fell significantly in all fenofibrate-treated groups. Although plasma total cholesterol levels fell significantly in fish oil-fed groups, fenofibrate treatments increased significantly plasma total cholesterol levels in these fish oil groups, but not in the group fed SO alone; however, hepatic triglyceride and total cholesterol levels markedly decreased in MO-or TO-fed mice. In lipid synthesis, the hepatic mRNA level of SREBP-1c was not reduced in either fish oil group; however, Insig-1 mRNA decreased in MO and TO feeding groups by about half and FAS or SCD-1 mRNA decreased significantly in MO and TO feeding groups, compared with the SO feeding group. In both fish oil groups, SREBP-2 mRNA decreased significantly and HMG-CoA reductase mRNA also decreased with/without fenofibrate. On the other hand, fenofibrate supplementation significantly induced the mRNA expression of AOX and UCP-2, which play a role in lipid catabolism, in all diets. CYP7A1 mRNA increased markedly in mice fed MO diet with fenofibrate, compared with TO diet with fenofibrate.

Conclusion: These data suggest that differences in dietary contents of EPA and DHA do not influence the inhibition of lipogenesis, and that fenofibrate supplementation stimulates fatty acid oxidation, regardless of the oil type; however, cholesterol catabolism was induced by a combination of EPA-rich fish oil and fenofibrate, which suggests that EPA has a greater synergistic ability for cholesterol catabolism induction by fenofibrate than DHA.