编辑推荐:
DHA(二十二碳六烯酸)因为对大脑有益而被俗称为“脑黄金”,然而人们一直不清楚DHA是如何被大脑吸收的。现在Duke-NUS的科学家们找到了这个问题的答案,他们鉴定了将DHA带入大脑的转运蛋白Mfsd2a,这一发现将有助于人们进一步理解DHA的作用机制。
生物通报道:DHA(二十二碳六烯酸)因为对大脑有益而被俗称为“脑黄金”,然而人们一直不清楚DHA是如何被大脑吸收的。现在Duke-NUS的科学家们找到了这个问题的答案,他们鉴定了将DHA带入大脑的转运蛋白Mfsd2a,这一发现将有助于人们进一步理解DHA的作用机制。
众所周知,DHA是人体必需的一种膳食营养,可以从海产品中获得。不少婴儿奶粉都将添加DHA作为一大卖点。
DHA是一种omega-3脂肪酸,它在大脑中的含量最为丰富,被认为对大脑功能有着至关重要的作用。但是大脑并不生产DHA,需要通过以下两种渠道进行摄取。在胎儿发育时,大脑从母体获得DHA。而成年人大脑从食物获得DHA,或摄取肝脏生产的DHA。(延伸阅读:The Scientist:Omega-3到底有什么用)
尽管DHA对大脑功能有益,但大脑吸收这种脂肪酸的机制一直是个谜。文章的资深作者,Duke-NUS的副教授David L. Silver介绍了解开这一谜题的重要性。
“如果能够阐明DHA进入大脑的机制,我们就可以利用这一信息促进它的定向吸收效率,开发改良版的营养添加剂。”
研究显示,缺乏Mfsd2a转运子的小鼠大脑比对照组小三分之一,这些小鼠出现了记忆和学习缺陷,而且表现出高水平的焦虑。研究人员发现,这些小鼠的学习、记忆和行为缺陷,与膳食中缺乏DHA的小鼠非常类似。
随后,研究团队通过生化实验证实,Mfsd2a缺陷型小鼠的确缺乏DHA。他们还意外地发现,Mfds2a转运的是溶血性磷脂酰胆碱(LPC)化学形态中的DHA。这一发现非常重要,因为LPC是主要由肝脏生产的一种磷脂,高水平存在于人类的血液中。过去人们一直认为LPC对细胞有毒,不清楚它们在体内有何作用。
研究人员总结道,Mfsd2a是胎儿大脑和成年人大脑摄取DHA的主要途径,而被转运的DHA存在于LPC的化学形态中。这篇文章于五月十二日发表在Nature杂志上,首次为人们提供了一个研究DHA缺乏及其功能的遗传学模型。
“我们的发现可以帮助人们更有效地将DHA整合在食物中,挖掘DHA促进大脑生长和功能的最大潜力。这对于胎儿发育时期没有获得足够DHA的婴儿来说特别有意义。”Dr Silver说。
生物通报道:叶予
生物通推荐原文摘要:
Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid
Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is essential for normal brain growth and cognitive function1, 2, 3, 4. Consistent with its importance in the brain, DHA is highly enriched in brain phospholipids5, 6, 7. Despite being an abundant fatty acid in brain phospholipids, DHA cannot be de novo synthesized in brain and must be imported across the blood–brain barrier, but mechanisms for DHA uptake in brain have remained enigmatic. Here we identify a member of the major facilitator superfamily—Mfsd2a (previously an orphan transporter)—as the major transporter for DHA uptake into brain. Mfsd2a is found to be expressed exclusively in endothelium of the blood–brain barrier of micro-vessels. Lipidomic analysis indicates that Mfsd2a-deficient (Mfsd2a-knockout) mice show markedly reduced levels of DHA in brain accompanied by neuronal cell loss in hippocampus and cerebellum, as well as cognitive deficits and severe anxiety, and microcephaly. Unexpectedly, cell-based studies indicate that Mfsd2a transports DHA in the form of lysophosphatidylcholine (LPC), but not unesterified fatty acid, in a sodium-dependent manner. Notably, Mfsd2a transports common plasma LPCs carrying long-chain fatty acids such LPC oleate and LPC palmitate, but not LPCs with less than a 14-carbon acyl chain. Moreover, we determine that the phosphor-zwitterionic headgroup of LPC is critical for transport. Importantly, Mfsd2a-knockout mice have markedly reduced uptake of labelled LPC DHA, and other LPCs, from plasma into brain, demonstrating that Mfsd2a is required for brain uptake of DHA. Our findings reveal an unexpected essential physiological role of plasma-derived LPCs in brain growth and function.
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