Pérez-Echarri Nerea, Pérez-Matute Patricia, Marcos-Gómez Beatriz, Marti Amelia, Martínez J Alfredo, Moreno-Aliaga María J
Department of Nutrition and Food Sciences, Physiology and Toxicology, University of Navarra, Pamplona, Spain.
J Nutr Biochem. 2009 Sep;20(9):705-14. doi: 10.1016/j.jnutbio.2008.06.013. Epub 2008 Sep 30.
The precise mechanisms by which omega-3 fatty acids improve fat metabolism are not completely understood. This study was designed to determine the effects of eicosapentaenoic acid (EPA) ethyl ester administration on the expression levels of several muscle, liver and adipose tissue genes involved in lipogenesis and fatty acid oxidation pathways. Male Wistar rats fed a standard diet (control animals) or a high-fat diet were treated daily by oral gavage with EPA ethyl ester (1g/kg) for 5 weeks. The high-fat diet caused a very significant increase in plasma cholesterol (P<.01) levels, which was reverted by EPA (P<.001). A significant decrease in circulating triglyceride levels (P<.05) was also observed in EPA-treated groups. EPA administration induced a significant down-regulation in some lipogenic genes such as muscle acetyl CoA carboxylase beta (ACC beta) (P<.05) and liver fatty acid synthase (FAS) (P<.05). Furthermore, a decrease in glucokinase (GK) gene expression was observed in EPA-treated animals fed a control diet (P<.01), whereas a significant increase in GK mRNA levels was found in groups fed a high-fat diet. On the other hand, no alterations in genes involved in beta-oxidation, such acetyl CoA synthase 4 (ACS4), acetyl CoA synthase 5 (ACS5) or acetyl CoA oxidase (ACO), were found in EPA-treated groups. Surprisingly and opposite to the expectations, a very significant decrease in the expression levels of liver PPARalpha (P<.01) was observed after EPA treatment. These findings show the ability of EPA ethyl ester treatment to down-regulate some genes involved in fatty acid synthesis without affecting the transcriptional activation of beta-oxidation-related genes.
ω-3脂肪酸改善脂肪代谢的确切机制尚未完全明确。本研究旨在确定二十碳五烯酸（EPA）乙酯给药对参与脂肪生成和脂肪酸氧化途径的多个肌肉、肝脏和脂肪组织基因表达水平的影响。给雄性Wistar大鼠喂食标准饮食（对照动物）或高脂饮食，每天通过口服灌胃给予EPA乙酯（1g/kg），持续5周。高脂饮食导致血浆胆固醇水平非常显著升高（P<0.01），而EPA可使其恢复正常（P<0.001）。在接受EPA治疗的组中还观察到循环甘油三酯水平显著降低（P<0.05）。给予EPA可导致一些脂肪生成基因显著下调，如肌肉中的乙酰辅酶A羧化酶β（ACCβ）（P<0.05）和肝脏中的脂肪酸合酶（FAS）（P<0.05）。此外，在喂食对照饮食的接受EPA治疗的动物中观察到葡萄糖激酶（GK）基因表达降低（P<0.01），而在喂食高脂饮食的组中发现GK mRNA水平显著升高。另一方面，在接受EPA治疗的组中，未发现参与β-氧化的基因，如乙酰辅酶A合酶4（ACS4）、乙酰辅酶A合酶5（ACS5）或乙酰辅酶A氧化酶（ACO）有改变。令人惊讶且与预期相反的是，EPA治疗后肝脏PPARα的表达水平非常显著降低（P<0.01）。这些发现表明，EPA乙酯治疗能够下调一些参与脂肪酸合成的基因，而不影响与β-氧化相关基因的转录激活。
