Interaction of Fenofibrate and Fish Oil in Relation to Lipid Metabolism in Mice

Abstract

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. J Atheroscler

Effect of dietary eicosapentaenoic and docosahexaenoic acid on expression of rat liver genes controlling cholesterol homeostasis and on plasma cholesterol level

“…The results of the present experiment regarding rat liver Hmgcr gene (Figure 1) do not agree with the data found in mice, where Hmgcr gene expression was decreased by EPA/DHA (Arai et al 2009a), by menhaden oil (EPA) (Arai et al 2009b), by FO (Hirako et al 2010) or by EPA alone (Sugiyama et al 2008). On the other hand, only tuna oil (DHA), but not menhaden oil (EPA) decreased expression of Ldlr in the study of Arai et al (2009b).…”

“…On the other hand, both Arai et al (2009a) and Arai et al (2009b) reported a decrease of SREBP-2 mRNA in EPA/DHA-fed mice. Similarly, SREBP-1c and SREBP-1 mRNA decreased in the liver of the FO-fed rats (Takahashi 2011) and n-3 PUFA-fed rats (Lu et al 2011), respectively.…”

Anti-Obesity Effect of Fish Oil and Fish Oil-Fenofibrate Combination in Female KK Mice

“…Our previous study also showed that fenofibrate treatment markedly increased plasma HDL-cholesterol in C57BL/6 mice 17) . The data presented here indicate that the increase of plasma total cholesterol in DHA FF fed mice is due to the increase of plasma HDL-cholesterol by the effect of fenofibrate.…”

“…In addition, the combination of EPA and DHA provided a stronger hypolipidemic effect than each alone 16) . In our previous study, consumption of different fish oils, specifically EPA-or DHA-rich fish oil, did not produce different effects on lipogenesis in C57BL/6J mice 17) . In this study, we decided to use KK mice that develop non-insulindependent diabetes mellitus with moderate obesity, insulin resistance and hyperlipidemia 18) .…”

Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma

“…Whether brain or circulating triacylglycerol levels are modifi ed by our dietary DHAenrichment regime remains to be explored. A longer period of DHA supplementation may be required, as suggested by the demonstration that -3-rich diets can lower plasma triacylglycerol (usually by 10-20%) in various strains of healthy mice but only after 4-16 weeks of supplemental -3 fatty acid intake (59)(60)(61).…”