Rapid β-oxidation of eicosapentaenoic acid in mouse brain: An in situ study

Rapid β-oxidation of eicosapentaenoic acid in mouse brain: An in situ study
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DOI:
10.1016/j.plefa.2009.01.005
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发表时间:
2009-02-01
影响因子:
3
通讯作者:
Bazinet, Richard P.
Bazinet, Richard P.
中科院分区:
医学4区
文献类型:
--
作者:
Chen, Chuck T.;Liu, Zhen;Bazinet, Richard P.

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脑磷脂脂肪酸谱分析显示,二碳五烯酸(EPA)和二十二碳六烯酸(DHA)分别选择性缺乏和富集。为了解释大脑脂肪酸水平的差异,我们假设EPA在进入大脑时被更快地氧化。野生型C57BL/6小鼠经原位脑灌注灌注C-14-EPA或C-14-DHA 40 s,然后用碳酸氢盐缓冲液洗去毛细血管中残留的放射性标记的多不饱和脂肪酸(PUFA)。提取c -14- pufa灌注的脑,进行中性脂质和磷脂脂肪酸的化学分析。根据其在水、总脂、中性脂和磷脂组分中的放射性,计算其分布体积(V-D, μ l/g)。C-14-EPA-和c -14- dha灌注样品的总脂质、中性脂质和总磷脂的V-D差异无统计学意义。然而,C-14-EPA的V-D是C-14-DHA的2.5倍(p = 0.025),表明其β -氧化比DHA更广泛。此外,在C-14-EPA灌注小鼠的脑磷脂中检测到放射性标记棕榈油酸(一种可以重新合成的脂肪酸),但在c -14- dha灌注小鼠的脑磷脂中检测不到,这表明EPA的β -氧化产物被循环到内源性脂肪酸生物合成途径中。这些发现表明,与DHA相比,脑磷脂中EPA的含量较低,这可能是DHA在被大脑吸收后迅速氧化的结果。2009爱思唯尔有限公司版权所有。
Analyses of brain phospholipid fatty acid profiles reveal a selective deficiency and enrichment in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. In order to account for this difference in brain fatty acid levels, we hypothesized that EPA is more rapidly beta-oxidized upon its entry into the brain. Wild-type C57BL/6 mice were perfused with either C-14-EPA or C-14-DHA via in situ cerebral perfusion for 40 s, followed by a bicarbonate buffer to wash out the residual radiolabeled polyunsaturated fatty acid (PUFA) in the capillaries. C-14-PUFA-perfused brains were extracted for chemical analyses of neutral lipid and phospholipid fatty acids. Based on the radioactivity in aqueous, total lipid, neutral lipid and phospholipid fractions, volume of distribution (V-D, mu l/g) was calculated. The V-D between C-14-EPA- and C-14-DHA-perfused samples was not statistically different for total lipid, neutral lipids or total phospholipids. However, the V-D of C-14-EPA in the aqueous fraction was 2.5 times higher than that of C-14-DHA (p = 0.025), suggesting a more extensive beta-oxidation than DHA. Furthermore, radiolabeled palmitoleic acid, a fatty acid that can be synthesized de novo, was detected in brain phospholipids from C-14-EPA but not from C-14-DHA-perfused mice suggesting that beta-oxidation products of EPA were recycled into endogenous fatty acid biosynthetic pathways. These findings suggest that low levels of EPA in brain phospholipids compared to DHA may be the result of its rapid beta-oxidation upon uptake by the brain. (C) 2009 Elsevier Ltd. All rights reserved.