Proteomic and lipidomic profiling of demyelinating lesions identifies fatty acids as modulators in lesion recovery

Horst Penkert, Alix Bertrand, Vini Tiwari, Stephan Breimann, Stephan A. Müller, Paul M. Jordan, Mathias J. Gerl, Christian Klose, Ludovico Cantuti-Castelvetri, Mar Bosch-Queralt, Ilya Levental, Stefan F. Lichtenthaler, Oliver Werz, Mikael Simons

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

After demyelinating injury of the central nervous system, resolution of the mounting acute inflammation is crucial for the initiation of a regenerative response. Here, we aim to identify fatty acids and lipid mediators that govern the balance of inflammatory reactions within demyelinating lesions. Using lipidomics, we identify bioactive lipids in the resolution phase of inflammation with markedly elevated levels of n-3 polyunsaturated fatty acids. Using fat-1 transgenic mice, which convert n-6 fatty acids to n-3 fatty acids, we find that reduction of the n-6/n-3 ratio decreases the phagocytic infiltrate. In addition, we observe accelerated decline of microglia/macrophages and enhanced generation of oligodendrocytes in aged mice when n-3 fatty acids are shuttled to the brain. Thus, n-3 fatty acids enhance lesion recovery and may, therefore, provide the basis for pro-regenerative medicines of demyelinating diseases in the central nervous system.

Original languageEnglish
Article number109898
JournalCell Reports
Volume37
Issue number4
DOIs
StatePublished - 26 Oct 2021
Externally publishedYes

Keywords

  • demyelination
  • inflammation resolution
  • lipids
  • microglia
  • myelin
  • remyelination

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