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

Laura Montani, Jorge A. Pereira, Camilla Norrmén, Hartmut B.F. Pohl, Elisa Tinelli, Martin Trötzmüller, Gianluca Figlia, Penelope Dimas, Belinda von Niederhäusern, Rachel Schwager, Sebastian Jessberger, Clay F. Semenkovich, Harald C. Köfeler, Ueli Suter

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1353-1368
Number of pages16
JournalJournal of Cell Biology
Volume217
Issue number4
DOIs
StatePublished - Apr 1 2018

Fingerprint

Dive into the research topics of 'De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination'. Together they form a unique fingerprint.

Cite this