Rewiring Neuronal Glycerolipid Metabolism Determines the Extent of Axon Regeneration.,Neuron

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Rewiring Neuronal Glycerolipid Metabolism Determines the Extent of Axon Regeneration.
Neuron ( IF 14.7 ) Pub Date : 2019-11-27 , DOI: 10.1016/j.neuron.2019.10.009
Chao Yang ₁ , Xu Wang ₂ , Jianying Wang ₃ , Xuejie Wang ₂ , Weitao Chen ₄ , Na Lu ₂ , Symeon Siniossoglou ₅ , Zhongping Yao ₃ , Kai Liu ₆

Affiliation

Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China; Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China.
Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
State Key Laboratory of Chirosciences, Food Safety and Technology Research Centre and Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China.
Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China.
Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China; Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China; Center of Systems Biology and Human Health, School of Science and Institute for Advanced Study, The Hong Kong University of Science and Technology, Hong Kong, China.

How adult neurons coordinate lipid metabolism to regenerate axons remains elusive. We found that depleting neuronal lipin1, a key enzyme controlling the balanced synthesis of glycerolipids through the glycerol phosphate pathway, enhanced axon regeneration after optic nerve injury. Axotomy elevated lipin1 in retinal ganglion cells, which contributed to regeneration failure in the CNS by favorably producing triglyceride (TG) storage lipids rather than phospholipid (PL) membrane lipids in neurons. Regrowth induced by lipin1 depletion required TG hydrolysis and PL synthesis. Decreasing TG synthesis by deleting neuronal diglyceride acyltransferases (DGATs) and enhancing PL synthesis through the Kennedy pathway promoted axon regeneration. In addition, peripheral neurons adopted this mechanism for their spontaneous axon regeneration. Our study reveals a critical role of lipin1 and DGATs as intrinsic regulators of glycerolipid metabolism in neurons and indicates that directing neuronal lipid synthesis away from TG synthesis and toward PL synthesis may promote axon regeneration.

中文翻译：

重新连接神经元甘油脂代谢决定轴突再生的程度。

成年神经元如何协调脂质代谢以再生轴突仍然不清楚。我们发现，消耗神经元lipin1（一种通过磷酸甘油途径控制甘油脂平衡合成的关键酶）可增强视神经损伤后的轴突再生。轴突切开术使视网膜神经节细胞中的lipin1升高，从而通过在神经元中产生甘油三酸酯（TG）储存脂质而不是磷脂（PL）膜脂质来促进中枢神经系统再生失败。lipin1耗尽诱导的再生需要TG水解和PL合成。通过删除神经元甘油二酸酯酰基转移酶（DGATs）减少TG合成，并通过Kennedy途径增强PL合成可促进轴突再生。此外，周围神经元采用这种机制自发性轴突再生。

更新日期：2019-11-28

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