De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination

J Cell Biol. 2018 Apr 2;217(4):1353-1368. doi: 10.1083/jcb.201706010. Epub 2018 Feb 6.


Myelination calls for a remarkable surge in cell metabolism to facilitate lipid and membrane production. Endogenous fatty acid (FA) synthesis represents a potentially critical process in myelinating glia. Using genetically modified mice, we show that Schwann cell (SC) intrinsic activity of the enzyme essential for de novo FA synthesis, fatty acid synthase (FASN), is crucial for precise lipid composition of peripheral nerves and fundamental for the correct onset of myelination and proper myelin growth. Upon FASN depletion in SCs, epineurial adipocytes undergo lipolysis, suggestive of a compensatory role. Mechanistically, we found that a lack of FASN in SCs leads to an impairment of the peroxisome proliferator-activated receptor (PPAR) γ-regulated transcriptional program. In agreement, defects in myelination of FASN-deficient SCs could be ameliorated by treatment with the PPARγ agonist rosiglitazone ex vivo and in vivo. Our results reveal that FASN-driven de novo FA synthesis in SCs is mandatory for myelination and identify lipogenic activation of the PPARγ transcriptional network as a putative downstream functional mediator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Fatty Acid Synthase, Type I / genetics
  • Fatty Acid Synthase, Type I / metabolism
  • Fatty Acids / biosynthesis*
  • Female
  • Lipogenesis* / drug effects
  • Lipogenesis* / genetics
  • Male
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Knockout
  • Myelin Sheath / metabolism*
  • Nerve Fibers, Myelinated / drug effects
  • Nerve Fibers, Myelinated / metabolism*
  • PPAR gamma / agonists
  • PPAR gamma / metabolism
  • Rosiglitazone / pharmacology
  • Schwann Cells / drug effects
  • Schwann Cells / metabolism*
  • Sciatic Nerve / cytology
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / metabolism*
  • Signal Transduction
  • Transcription, Genetic


  • Fatty Acids
  • PPAR gamma
  • Rosiglitazone
  • Fatty Acid Synthase, Type I