Mice raised on milk transgenically enriched with n-3 PUFA have increased brain docosahexaenoic acid

Mice raised on milk transgenically enriched with n-3 PUFA have increased brain docosahexaenoic acid
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DOI:
10.1007/s11745-006-5003-z
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发表时间:
2006-06-01
期刊:
影响因子:
1.9
通讯作者:
Van Eenennaam, Alison L.
Van Eenennaam, Alison L.
中科院分区:
医学4区
文献类型:
--
作者:
Kao, Beth T.;DePeters, Edward J.;Van Eenennaam, Alison L.

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大脑含有高水平的长链n - 3脂肪酸DHA(22:6n - 3),主要存在于灰质和突触体中。充足的DHA摄入对神经系统的最佳功能至关重要,尤其是对婴儿而言。建议在婴儿配方奶粉中添加与人类母乳中含量相似的DHA,这对新生儿在生化和功能方面有益。我们通过在哺乳期诱导的山羊β - 酪蛋白启动子的控制下表达秀丽隐杆线虫n - 3脂肪酸去饱和酶,培育出了乳汁中n - 3多不饱和脂肪酸含量升高的转基因小鼠。为了研究食用富含n - 3的乳汁对产后的影响,我们比较了由转基因母鼠喂养的幼鼠和由非转基因母鼠喂养的幼鼠的生长情况以及大脑和血浆脂肪酸组成。在转基因小鼠乳汁的磷脂部分观察到花生四烯酸(ARA,20:4n - 6)显著减少,同时n - 3多不饱和脂肪酸增加。转基因和对照乳汁磷脂部分的n - 6:n - 3脂肪酸比例分别为4.7和34.5。由转基因母鼠哺育的断奶小鼠大脑脂肪酸中DHA和DPA(22:5n - 6)分别占15.1%和2.8%,而由对照母鼠哺育的断奶小鼠分别为6.9%和9.2%。这种转基因小鼠模型提供了一种独特的方法,将高n - 6:n - 3脂肪酸比例的孕期环境所产生的影响和胎儿编程与提供不同n - 6:n - 3脂肪酸比例的乳汁的产后营养影响区分开来。
The brain contains high levels of the long-chain n-3 FA DHA(22:6n-3), mainly in the gray matter and synaptosomes. Adequate intake of DHA is crucial for optimal nervous system function, particularly in infants. Supplementation of infant formulas with DHA at levels similar to human breast milk is recommended for biochemical and functional benefits to neonates. We generated transgenic mice that produce elevated levels of n-3 PUFA in their milk by expressing the Caenorhabditis elegans n-3 FA desaturase under the control of a lactation-induced goat beta-casein promoter. To examine the postnatal effects of consuming the n-3-enriched milk, we compared the growth and brain and plasma FA composition of mouse pups raised on milk from transgenic dams with those observed for pups raised on milk from nontransgenic dams. A significant decrease in arachidonic acid (ARA, 20:4n-6) and concomitant increases in n-3 PUFA were observed in the phospholipid fraction of transgenic mouse milk. The n-6:n-3 FA ratios were 4.7 and 34.5 for the transgenic and control milk phospholipid fractions, respectively. DHA and DPA (22:5n-6) comprised 15.1% and 2.8% of brain FA from weanling mice nursed on transgenic dams, as compared with 6.9% and 9.2% for weanling mice nursed on control dams, respectively. This transgenic mouse model offers a unique approach to disassociate the effects and fetal programming resulting from a high n-6:n-3 FA ratio gestational environment from the postnatal nutritional effects of providing milk with differing n-6:n-3 FA ratios.