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首页> 外文期刊>Cell metabolism >The Glia-Neuron Lactate Shuttle and Elevated ROS Promote Lipid Synthesis in Neurons and Lipid Droplet Accumulation in Glia via APOE/D
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The Glia-Neuron Lactate Shuttle and Elevated ROS Promote Lipid Synthesis in Neurons and Lipid Droplet Accumulation in Glia via APOE/D

机译：Glia-neuron乳酸乳酸梭和升高的ROS通过Apoe / D促进神经元和脂质液滴积聚的脂质合成

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Summary Elevated reactive oxygen species (ROS) induce the formation of lipids in neurons that are transferred to glia, where they form lipid droplets (LDs). We show that glial and neuronal monocarboxylate transporters (MCTs), fatty acid transport proteins (FATPs), and apolipoproteins are critical for glial LD formation. MCTs enable glia to secrete and neurons to absorb lactate, which is converted to pyruvate and acetyl-CoA in neurons. Lactate metabolites provide a substrate for synthesis of fatty acids, which are processed and transferred to glia by FATP and apolipoproteins. In the presence of high ROS, inhibiting lactate transfer or lowering FATP or apolipoprotein levels decreases glial LD accumulation in flies and in primary mouse glial-neuronal cultures. We show that human APOE can substitute for a fly glial apolipoprotein and that APOE4, an Alzheimer’s disease susceptibility allele, is impaired in lipid transport and promotes neurodegeneration, providing insights into disease mechanisms. Graphical Abstract Display Omitted Highlights ? Glia-derived lactate fuels neuronal lipid production ? Elevated levels of ROS promote lipid production in neurons ? Neuronal lipids are transported to glia via apolipoproteins E and D ? APOE4’s inability to transport lipids for LD formation leads to neurodegeneration Liu et?al. unravel an evolutionarily conserved mechanism which brings neuron-glia metabolic cooperation full circle. They show that glial lactate can fuel neuronal lipogenesis in response to ROS; in turn, neuronal lipids are transported and stored in glia as lipid droplets. The inability to transport lipids to glia for lipid droplet formation leads to accelerated neurodegeneration under stress.
机译：发明内容升高的活性氧（ROS）诱导形成转移到胶质胶质的神经元中的脂质的形成，在那里它们形成脂液滴（LDS）。我们表明胶质和神经元单羧酸酯转运蛋白（MCT），脂肪酸输送蛋白（FATPS）和载脂蛋白对胶质LD形成至关重要。 MCTS使Glia能够分泌和神经元以吸收乳酸，其在神经元中转化为丙酮酸和乙酰辅酶。乳酸代谢物提供用于合成脂肪酸的底物，其通过FATP和载脂蛋白加工并转移至胶质胶质。在高ROS存在下，抑制乳酸转移或降低的FATP或载脂蛋白水平降低苍蝇和初级小鼠神经元培养物中的胶质LD积累。我们表明，人类Apoe可以替代苍蝇蚜蛋白，并且ApoE4，Alzheimer的疾病易感性等位基因在脂质运输中受到损害，并促进神经变性，提供疾病机制的见解。图形抽象显示省略了亮点？ Glia衍生的乳酸燃料燃料神经元脂质生产？ ROS的升高促进神经元的脂质生产？通过载脂蛋白E和D将神经元脂质运输到Glia？ Apoe4无法运输LD形成的脂质，导致神经变性Liu et？Al。揭开一种进化的保守机制，带来全圈的神经元 - 胶质胶质组合。它们表明胶质乳酸味可以响应ROS促进神经元脂肪生成;反过来，神经元脂质被运输并储存在胶质胶片中作为脂质液滴。对于脂质液滴形成的无能为力地运输脂质，导致应力下加速神经变性。

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