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母体n-3脂肪酸缺乏后胎鼠对羊膜腔内注射的氘标记必需脂肪酸的代谢转化

Metabolic conversion of intra-amniotically-injected deuterium-labeled essential fatty acids by fetal rats following maternal n-3 fatty acid deficiency.

作者信息

Yavin Ephraim, Lin Yu Hong, Brand Annette, Salem Norman

机构信息

National Institute on Alcohol Abuse and Alcoholism NIH, Bethesda, MD, USA; Department of Neurobiology, Weizmann Institute of Science, Rehovot, IL 76100.

National Institute on Alcohol Abuse and Alcoholism NIH, Bethesda, MD, USA.

出版信息

Biochim Biophys Acta. 2014 Sep;1841(9):1336-44. doi: 10.1016/j.bbalip.2014.06.008. Epub 2014 Jun 21.

DOI:10.1016/j.bbalip.2014.06.008
PMID:24960100
Abstract

Accumulation of polyunsaturated fatty acids (PUFA) in the fetal brain is accomplished predominantly via a highly selective flow of docosahexaenoic acid (22:6n-3, DHA) and arachidonic acid (20:4n-6, AA) through the placenta. Little is known regarding the endogenous capability of the fetus to generate its own DHA and AA from lower homologues such as linolenic (18:3n-3, ALA) and linoleic (18:2n-6, LA) acids, respectively. Deuterium-labeled d5-ALA and d5-LA at millimolar concentrations were injected directly into the amniotic fluid in order to investigate maternal-independent metabolic conversion of the stable isotopes in brain and liver of the fetus near delivery. After 48h under adequate maternal diet, the levels of d5-ALA metabolites in the fetal brain and fetal liver were 45±2.2 pmol/mg and 86±4 pmol/mg of which 79% and 63.6% were comprised of d5-DHA. At this time point, incorporation of d5-LA metabolites was 103±5 pmol/mg and 772±46 pmol/mg for brain and liver, of which 50% and 30% were comprised of d5-AA. Following sustained maternal dietary ALA deficiency, the levels of total d5-ALA derived metabolites in the fetal brain and fetal liver were increased to 231 pmol/mg and 696 pmol/mg of which 71% and 26% were comprised of d5-DHA. From the time course and relative rates of d5-ALA precursor displacement by d5-DHA in cellular phosphoglycerides, it is concluded that the fetal rat brain can generate its own DHA from its d5-ALA precursors particularly under dietary stress.

摘要

胎儿大脑中多不饱和脂肪酸(PUFA)的积累主要是通过二十二碳六烯酸(22:6n-3,DHA)和花生四烯酸(20:4n-6,AA)经胎盘的高度选择性流动来完成的。关于胎儿从较低同系物如亚麻酸(18:3n-3,ALA)和亚油酸(18:2n-6,LA)分别生成自身DHA和AA的内源性能力,人们了解甚少。为了研究接近分娩时胎儿大脑和肝脏中稳定同位素的母体非依赖性代谢转化,将毫摩尔浓度的氘标记的d5-ALA和d5-LA直接注入羊水。在母体饮食充足的情况下48小时后,胎儿大脑和胎儿肝脏中d5-ALA代谢物的水平分别为45±2.2 pmol/mg和86±4 pmol/mg,其中79%和63.6%由d5-DHA组成。在这个时间点,大脑和肝脏中d5-LA代谢物的掺入量分别为103±5 pmol/mg和772±46 pmol/mg,其中50%和30%由d5-AA组成。在母体持续饮食ALA缺乏后,胎儿大脑和胎儿肝脏中总d5-ALA衍生代谢物的水平分别增加到231 pmol/mg和696 pmol/mg,其中71%和26%由d5-DHA组成。从细胞磷酸甘油酯中d5-DHA取代d5-ALA前体的时间进程和相对速率可以得出结论,特别是在饮食应激情况下,胎鼠大脑可以从其d5-ALA前体生成自身的DHA。

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