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

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 enzym...

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Autores principales: Montani, Laura, Pereira, Jorge A., Norrmén, Camilla, Pohl, Hartmut B.F., Tinelli, Elisa, Trötzmüller, Martin, Figlia, Gianluca, Dimas, Penelope, von Niederhäusern, Belinda, Schwager, Rachel, Jessberger, Sebastian, Semenkovich, Clay F., Köfeler, Harald C., Suter, Ueli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881495/
https://www.ncbi.nlm.nih.gov/pubmed/29434029
http://dx.doi.org/10.1083/jcb.201706010
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author Montani, Laura
Pereira, Jorge A.
Norrmén, Camilla
Pohl, Hartmut B.F.
Tinelli, Elisa
Trötzmüller, Martin
Figlia, Gianluca
Dimas, Penelope
von Niederhäusern, Belinda
Schwager, Rachel
Jessberger, Sebastian
Semenkovich, Clay F.
Köfeler, Harald C.
Suter, Ueli
author_facet Montani, Laura
Pereira, Jorge A.
Norrmén, Camilla
Pohl, Hartmut B.F.
Tinelli, Elisa
Trötzmüller, Martin
Figlia, Gianluca
Dimas, Penelope
von Niederhäusern, Belinda
Schwager, Rachel
Jessberger, Sebastian
Semenkovich, Clay F.
Köfeler, Harald C.
Suter, Ueli
author_sort Montani, Laura
collection PubMed
description 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.
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spelling pubmed-58814952018-04-04 De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination Montani, Laura Pereira, Jorge A. Norrmén, Camilla Pohl, Hartmut B.F. Tinelli, Elisa Trötzmüller, Martin Figlia, Gianluca Dimas, Penelope von Niederhäusern, Belinda Schwager, Rachel Jessberger, Sebastian Semenkovich, Clay F. Köfeler, Harald C. Suter, Ueli J Cell Biol Research Articles 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. Rockefeller University Press 2018-04-02 /pmc/articles/PMC5881495/ /pubmed/29434029 http://dx.doi.org/10.1083/jcb.201706010 Text en © 2018 Montani et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Montani, Laura
Pereira, Jorge A.
Norrmén, Camilla
Pohl, Hartmut B.F.
Tinelli, Elisa
Trötzmüller, Martin
Figlia, Gianluca
Dimas, Penelope
von Niederhäusern, Belinda
Schwager, Rachel
Jessberger, Sebastian
Semenkovich, Clay F.
Köfeler, Harald C.
Suter, Ueli
De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination
title De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination
title_full De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination
title_fullStr De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination
title_full_unstemmed De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination
title_short De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination
title_sort de novo fatty acid synthesis by schwann cells is essential for peripheral nervous system myelination
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881495/
https://www.ncbi.nlm.nih.gov/pubmed/29434029
http://dx.doi.org/10.1083/jcb.201706010
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