Abstract：
α-Tocopherol (α-T) is a vitamin, but the reasons for the α-T requirement are controversial. Given that α-T deficiency was first identified in embryos, we studied to the premier model of vertebrate embryo development, the zebrafish embryo. We developed an α-T-deficient diet for zebrafish and used fish consuming this diet to produce α-T deficient (E-) embryos. We showed that α-T deficiency causes increased lipid peroxidation, leading to metabolic dysregulation that impacts both biochemical and morphological changes at very early stages in development. These changes occur at an early developmental window, which takes place prior to an analogous time to when a human knows she is pregnant. We found that α-T limits the chain reaction of lipid peroxidation and protects metabolic pathways and integrated gene expression networks that control embryonic development. Importantly, not only is α-T critical during early development, but the neurodevelopmental process is highly dependent on α-T trafficking by the α-T transfer protein (TTPa). Data from both gene expression and evaluation of the metabolome in E- embryos suggest that the activity of the mechanistic Target of Rapamycin (mTOR) signaling pathway is dysregulated-mTOR is a master regulatory mechanism, which controls both metabolism and neurodevelopment. Our findings suggest that TTPa is needed not only for regulation of plasma α-T in adults but is a key regulator during embryogenesis.
摘要：
α-生育酚（α-T）是一种维生素，但α-T要求的原因是有争议的。鉴于α-T缺陷首先在胚胎中被发现，我们研究了脊椎动物胚胎发育的首要模型，斑马鱼胚胎.我们为斑马鱼开发了一种缺乏α-T的饮食，并使用食用这种饮食的鱼产生缺乏α-T（E-）的胚胎。我们发现α-T缺乏导致脂质过氧化增加，导致代谢失调，在发育的早期阶段影响生化和形态变化。这些变化发生在早期发育窗口，这发生在一个类似于人类知道自己怀孕的时间之前。我们发现α-T限制了脂质过氧化的连锁反应，并保护了控制胚胎发育的代谢途径和整合的基因表达网络。重要的是,α-T不仅在早期发育过程中至关重要，但是神经发育过程高度依赖于α-T转移蛋白（TTPa）的α-T运输。来自E-胚胎中代谢组的基因表达和评估的数据表明，雷帕霉素（mTOR）信号通路的机制靶标的活性失调-mTOR是一种主要的调节机制，控制新陈代谢和神经发育。我们的发现表明，TTPa不仅是成人血浆α-T调节所必需的，而且是胚胎发育过程中的关键调节剂。
