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

Interaction of Fenofibrate and Fish Oil in Relation to Lipid Metabolism in Mice
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DOI:
10.5551/jat.e463
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发表时间:
2009-06-01
影响因子:
4.4
通讯作者:
Matsumoto, Akiyo
Matsumoto, Akiyo
中科院分区:
医学2区
文献类型:
--
作者:
Arai, Takeshi;Kim, Hyoun-ju;Matsumoto, Akiyo

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目的:方法:雌性C57 BL/6 J小鼠分别饲喂含红花油(SO)、富含EPA的鲱鱼油(MO)和富含DHA的金枪鱼油(TO)的纯饲粮,同时添加或不添加0.1%非诺贝特,连续8周。在实验结束时,我们测量了血浆脂质和肝脏甘油三酯和胆固醇,和脂肪生成和lipidolytic基因的肝脏mRNA表达。结果:血浆TG水平下降,在组中喂养MO或TO单独和下降显着在所有非诺贝特治疗组。虽然鱼油喂养组的血浆总胆固醇水平显著下降,但非诺贝特治疗显著增加了这些鱼油组的血浆总胆固醇水平,但在SO单独喂养组中没有增加;然而,MO或TO喂养小鼠的肝脏甘油三酯和总胆固醇水平显著降低。在脂质合成中,与SO喂养组相比,在任一鱼油组中,SREBP-1c的肝脏mRNA水平均未降低;然而,在MO和TO喂养组中,Insig-1 mRNA降低约一半,并且在MO和TO喂养组中FAS或SCD-1 mRNA显著降低。在两个鱼油组中,SREBP-2 mRNA显著降低,HMG-CoA还原酶mRNA也降低,有/无fenoribrate。另一方面,非诺贝特的补充显着诱导AOX和UCP-2的mRNA表达,这在脂质代谢中发挥作用,在所有的饮食。结论:膳食中EPA和DHA含量的差异不影响对脂肪生成的抑制作用,而非诺贝特的补充刺激脂肪酸氧化,与油的种类无关;然而,富含EPA的鱼油和非诺贝特的组合诱导了胆固醇代谢紊乱,这表明,
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 fenoribrate. 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