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  3. Rewiring Neuronal Glycerolipid Metabolism Determines the Extent of Axon Regeneration

Rewiring Neuronal Glycerolipid Metabolism Determines the Extent of Axon Regeneration

  • Neuron. 2020 Jan 22;105(2):276-292.e5. 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
Affiliations

Affiliations

  • 1 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.
  • 2 Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
  • 3 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.
  • 4 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.
  • 5 Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
  • 6 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. Electronic address: [email protected].
PMID: 31786011 DOI: 10.1016/j.neuron.2019.10.009
Abstract

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.

Keywords

DGAT1; DGAT2; Lipin1; axon regeneration; glycerolipid; phospholipid; retinal ganglion cell; triglyceride.

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