Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain.
ATP Binding Cassette Transporter 1
/ metabolism
Animals
Brain
/ pathology
Cell Line
Cholesterol
/ metabolism
Endocytosis
Fatty Acids
/ metabolism
Foam Cells
/ metabolism
Humans
Inflammation
/ pathology
Macrophages
/ enzymology
Mice
Microglia
/ enzymology
Myelin Sheath
/ metabolism
Phagocytes
/ pathology
Phenotype
Protein Kinase C-delta
/ metabolism
Stearoyl-CoA Desaturase
/ deficiency
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
04 05 2020
04 05 2020
Historique:
received:
05
09
2019
revised:
12
12
2019
accepted:
24
01
2020
entrez:
26
2
2020
pubmed:
26
2
2020
medline:
29
12
2020
Statut:
ppublish
Résumé
Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Macrophages and microglia are crucially involved in the formation and repair of demyelinated lesions. Here we show that myelin uptake temporarily skewed these phagocytes toward a disease-resolving phenotype, while sustained intracellular accumulation of myelin induced a lesion-promoting phenotype. This phenotypic shift was controlled by stearoyl-CoA desaturase-1 (SCD1), an enzyme responsible for the desaturation of saturated fatty acids. Monounsaturated fatty acids generated by SCD1 reduced the surface abundance of the cholesterol efflux transporter ABCA1, which in turn promoted lipid accumulation and induced an inflammatory phagocyte phenotype. Pharmacological inhibition or phagocyte-specific deficiency of Scd1 accelerated remyelination ex vivo and in vivo. These findings identify SCD1 as a novel therapeutic target to promote remyelination.
Identifiants
pubmed: 32097464
pii: 133840
doi: 10.1084/jem.20191660
pmc: PMC7201924
pii:
doi:
Substances chimiques
ATP Binding Cassette Transporter 1
0
Fatty Acids
0
Cholesterol
97C5T2UQ7J
Stearoyl-CoA Desaturase
EC 1.14.19.1
Protein Kinase C-delta
EC 2.7.11.13
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK062388
Pays : United States
Informations de copyright
© 2020 Bogie et al.
Déclaration de conflit d'intérêts
Disclosures: The authors declare no competing interests exist.
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