alpha-linolenic acid reduces the lovastatin-induced rise in arachidonic acid and elevates cellular lipoprotein eicosapentaenoic and docosahexaenoic acid levels in Hep G2 cells
alpha-linolenic acid reduces the lovastatin-induced rise in arachidonic acid and elevates cellular lipoprotein eicosapentaenoic and docosahexaenoic acid levels in Hep G2 cells
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DOI：
10.1016/0955-2863(96)00080-0
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发表时间：
1996-08-01
影响因子：
5.6
通讯作者：
Weber, PC
中科院分区：
文献类型：
--
作者：
Hrboticky, N;Zimmer, B;Weber, PC
据报道，接受3-羟基-3-甲基辅酶A（HMG-CoA）还原酶抑制剂治疗的患者血浆花生四烯酸（20：4 omega 6）水平升高。我们以前已经表明，这种作用与通过脂肪酸去饱和酶增加亚油酸（18：2 ω 6）转化为20：4 ω 6有关，并导致生物有效类二十烷酸的形成增加。因为脂肪酸去饱和酶也作用于脂肪酸，并且因为长链ω 3脂肪酸抵消了ω 6脂肪酸的许多生理作用，我们现在检查α-亚麻酸（18：3 ω 3）补充剂对洛伐他汀诱导的细胞和脂蛋白脂肪酸水平变化的影响。将人肝癌Hep G2细胞与洛伐他汀（10 μ mol/L）或其载体二甲基亚砜（DMSO，终浓度0.1%）孵育72小时，并与白蛋白结合的18：3 ω 3（40 μ mol/L）单独孵育或与不同比例的18：3 ω 3至18：2 ω 6孵育最后24小时。与对照细胞相比，洛伐他汀处理的细胞将更多的18：3 ω 3转化为二十碳五烯酸（20：5 ω 3）和二十二碳六烯酸（22：6 ω 3），这些酸以增加的量掺入这些细胞分泌的细胞磷脂和脂质中。在补充18：3 omega 3的细胞中，细胞和分泌脂质中20：4 omega 6水平的洛伐他汀介导的增加也显著降低。18：3欧米茄3补充剂对洛伐他汀诱导的欧米茄6和欧米茄3脂肪酸组成变化的影响取决于18：3欧米茄3/18：2欧米茄6补充比例。目前的研究表明，先前描述的HMGCoA还原酶抑制剂对多不饱和脂肪酸代谢的影响可以通过饮食18：3 omega 3/18：2 omega 6比例进行调节。
Increased plasma arachidonic acid (20:4 omega 6) levels have been reported in patients undergoing 3-hydroxy-3-methyl coenzyme A (HMG-CoA) reductase inhibitor therapy. We have previously shown that this effect is related to an increased conversion of linoleic acid (18:2 omega 6) to 20:4 omega 6 via the fatty acid desaturases and results in an increased formation of biologically potent eicosanoids. Because fatty acid desaturases also act on of fatty acids, and because the long chain omega 3 fatty acids counterbalance many of the physiological effects of omega 6 fatty acids, we now examine the effects of alpha-linolenic acid (18:3 omega 3) supplementation on the lovastatin-induced changes in cellular and lipoprotein fatty acid levels. Human hepatoma Hep G2 cells were incubated with lovastatin (10 mu mol/L) or its carrier dimethyl sulphoxide (DMSO, final concentration 0.1%) for 72 hr and with albumin-bound 18:3 omega 3 (40 mu mol/L) alone or with different ratios of 18:3 omega 3 to 18:2 omega 6 for the last 24 hr. In comparison with control cells, lovastatin-treated cells converted more 18:3 omega 3 into eicosapentaenoic (20:5 omega 3) and docosahexaenoic (22:6 omega 3) acids, which were incorporated in increasing amounts in cellular phospholipids and lipids secreted by these cells. The lovastatin-mediated increase in 20:4 omega 6 levels in cellular and secreted lipids was also significantly reduced in 18:3 omega 3-supplemented cells. The effect of 18:3 omega 3 supplementation on the lovastatin-induced changes in omega 6 and omega 3 fatty acid composition was dependent on the 18:3 omega 3/18:2 omega 6 supplementation ratio. The present studies suggest that the previously described effects of HMGCoA reductase inhibitors on polyunsaturated fatty acid metabolism can be modulated by the dietary 18:3 omega 3/18:2 omega 6 ratio.