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

Montani, L; Pereira, JA; Norrmen, C; Pohl, HBF; Tinelli, E; Troetzmuller, M; Figlia, G; ... Suter, U; + view all (2018) De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination. Journal of Cell Biology , 217 (4) pp. 1353-1368. 10.1083/jcb.201706010. Green open access

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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.

Type: Article
Title: De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination
Open access status: An open access version is available from UCL Discovery
DOI: 10.1083/jcb.201706010
Publisher version: http://doi.org/10.1083/jcb.201706010
Language: English
Additional information: Copyright © 2018 Montani et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10070650
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