Ide Takashi, Takahashi Yoko, Kushiro Masayo, Tachibana Masayoshi, Matsushima Yoshibumi
Laboratory of Nutritional Biochemistry, National Food Research Institute, 2-1-12 Kannondai, Tsukuba 305-8642, Japan.
J Nutr Biochem. 2004 Mar;15(3):169-78. doi: 10.1016/j.jnutbio.2003.11.001.
N-3 fatty acids exert a potent serum lipid-lowering effect in rodents mainly by affecting hepatic fatty acid oxidation and synthesis. However, it has been observed that fish oil and docosahexaenoic acid ethyl ester do not lower serum lipid levels in apolipoprotein E (apoE)-knockout (Apoetm1Unc) mice generated by gene targeting. To test the hypothesis that apoE expression is required for n-3 fatty acid-dependent regulation of serum lipid levels and hepatic fatty acid metabolism, we examined the effect of fish oil and n-3 fatty acid ethyl esters on the activity and gene expression of hepatic enzymes involved in fatty acid oxidation and synthesis using an alternative apoE-deficient mouse model with the BALB/c genetic background (BALB/c.KOR-Apoeshl). ApoE-deficient mice were fed diets containing 9.4% palm oil, fish oil, or 5.4% palm oil and 1% EPA plus 3% DHA ethyl esters for 15 days. In contrast to the reported data on apoE-knockout mice, fish oil and n-3 fatty acid ethyl esters greatly decreased serum triacylglycerol, cholesterol, and phospholipid levels in the Apoeshl mice. The decreases were greater with fish oil than with ethyl esters. The alterations by dietary n-3 fatty acids of serum lipid levels were accompanied by parallel changes in the activity and mRNA levels of enzymes involved in hepatic fatty acid oxidation and synthesis. The reason for the discrepancy between the results of the current study and previous studies is unknown. However, our study at least indicates that a lack of apoE expression does not necessarily accompany deficits in the n-3 fatty acid-dependent regulation of serum lipid levels and hepatic fatty acid metabolism.
N-3脂肪酸主要通过影响肝脏脂肪酸氧化和合成，对啮齿动物产生显著的降血脂作用。然而，据观察，鱼油和二十二碳六烯酸乙酯并不能降低通过基因靶向产生的载脂蛋白E（apoE）基因敲除（Apoetm1Unc）小鼠的血脂水平。为了验证apoE表达是n-3脂肪酸依赖性调节血脂水平和肝脏脂肪酸代谢所必需的这一假设，我们使用具有BALB/c遗传背景的另一种apoE缺陷小鼠模型（BALB/c.KOR-Apoeshl），研究了鱼油和n-3脂肪酸乙酯对参与脂肪酸氧化和合成的肝脏酶活性和基因表达的影响。给apoE缺陷小鼠喂食含9.4%棕榈油、鱼油或5.4%棕榈油加1%二十碳五烯酸（EPA）加3%二十二碳六烯酸（DHA）乙酯的饲料15天。与关于apoE基因敲除小鼠的报道数据相反，鱼油和n-3脂肪酸乙酯显著降低了Apoeshl小鼠的血清三酰甘油、胆固醇和磷脂水平。鱼油的降低作用比乙酯更大。膳食n-3脂肪酸引起的血脂水平变化伴随着肝脏脂肪酸氧化和合成相关酶活性和mRNA水平的平行变化。本研究结果与先前研究结果存在差异的原因尚不清楚。然而，我们的研究至少表明，apoE表达的缺失并不一定伴随着n-3脂肪酸依赖性血脂水平调节和肝脏脂肪酸代谢的缺陷。
