Skip to Content
Merck
  • De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination.

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

The Journal of cell biology (2018-02-13)
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
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-74, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Oil Red O solution, 0.5% in isopropanol
Avanti
21:0-22:6 PC, Avanti Research - A Croda Brand LM1003, methanol solution
Avanti
12:0-13:0 PI, Avanti Research - A Croda Brand LM1500, methanol solution
Sigma-Aldrich
Anti-Po Antibody, Chemicon®, from chicken
Avanti
17:0-20:4 PE, Avanti Research - A Croda Brand LM1102, methanol solution
Avanti
17:0-20:4 PS, Avanti Research - A Croda Brand LM1302, methanol solution