Format

Send to

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

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

Author information

1
Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology, ETH Zürich, Zürich, Switzerland laura.montani@biol.ethz.ch.
2
Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology, ETH Zürich, Zürich, Switzerland.
3
Lipidomics Center for Medical Research, Medical University, Graz, Austria.
4
Brain Research Institute, University of Zürich, Zürich, Switzerland.
5
Division of Endocrinology, Metabolism and Lipid Research, Washington University Medical School, St. Louis, MO.
6
Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology, ETH Zürich, Zürich, Switzerland usuter@biol.ethz.ch.

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.

PMID:
29434029
PMCID:
PMC5881495
DOI:
10.1083/jcb.201706010
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center