Journal
JOURNAL OF CELL BIOLOGY
Volume 217, Issue 4, Pages 1352-1367Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201706010
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Funding
- Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung
- Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung Marie Heim-Voegtlin fellowship [PMP DP3 139610]
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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) gamma-regulated transcriptional program. In agreement, defects in myelination of FASN-deficient SCs could be ameliorated by treatment with the PPAR. 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 PPAR. transcriptional network as a putative downstream functional mediator.
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