Igarashi Miki, Kim Hyung-Wook, Gao Fei, Chang Lisa, Ma Kaizong, Rapoport Stanley I
National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Biochim Biophys Acta. 2012 Sep;1821(9):1235-43. doi: 10.1016/j.bbalip.2011.11.002. Epub 2011 Nov 30.
Docosapentaenoic acid (DPAn-6, 22:5n-6) is an n-6 polyunsaturated fatty acid (PUFA) whose brain concentration can be increased in rodents by dietary n-3 PUFA deficiency, which may contribute to their behavioral dysfunction. We used our in vivo intravenous infusion method to see if brain DPAn-6 turnover and metabolism also were altered with deprivation. We studied male rats that had been fed for 15 weeks post-weaning an n-3 PUFA adequate diet containing 4.6% alpha-linolenic acid (α-LNA, 18:3n-3) or a deficient diet (0.2% α-LNA), each lacking docosahexaenoic acid (22:6n-3) and arachidonic acid (AA, 20:4n-6). [1-(14)C]DPAn-6 was infused intravenously for 5min in unanesthetized rats, after which the brain underwent high-energy microwaving, and then was analyzed. The n-3 PUFA deficient compared with adequate diet increased DPAn-6 and decreased DHA concentrations in plasma and brain, while minimally changing brain AA concentration. Incorporation rates of unesterified DPAn-6 from plasma into individual brain phospholipids were increased 5.2-7.7 fold, while turnover rates were increased 2.1-4.7 fold. The observations suggest that increased metabolism and brain concentrations of DPAn-6 and its metabolites, together with a reduced brain DHA concentration, contribute to behavioral and functional abnormalities reported with dietary n-3 PUFA deprivation in rodents. (196 words).
二十二碳五烯酸(DPAn - 6,22:5n - 6)是一种n - 6多不饱和脂肪酸(PUFA),在啮齿动物中,膳食中n - 3多不饱和脂肪酸缺乏时,其大脑中的浓度会升高,这可能导致它们出现行为功能障碍。我们使用体内静脉输注方法来观察大脑中DPAn - 6的周转和代谢是否也会因缺乏n - 3多不饱和脂肪酸而发生改变。我们研究了雄性大鼠,这些大鼠在断奶后15周被喂食含4.6%α-亚麻酸(α-LNA,18:3n - 3)的n - 3多不饱和脂肪酸充足饮食或缺乏饮食(0.2%α-LNA),两种饮食均缺乏二十二碳六烯酸(22:6n - 3)和花生四烯酸(AA,20:4n - 6)。在未麻醉的大鼠中静脉输注[1 - (14)C]DPAn - 6 5分钟,之后对大脑进行高能微波处理,然后进行分析。与充足饮食相比,n - 3多不饱和脂肪酸缺乏饮食使血浆和大脑中的DPAn - 6浓度升高,DHA浓度降低,而大脑中AA浓度变化极小。未酯化的DPAn - 6从血浆掺入个体脑磷脂的掺入率增加了5.2至7.7倍,而周转率增加了2.1至4.7倍。这些观察结果表明,DPAn - 6及其代谢产物的代谢增加和大脑浓度升高,以及大脑中DHA浓度降低,导致了啮齿动物膳食n - 3多不饱和脂肪酸缺乏时所报告的行为和功能异常。(196字)