1. Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain
- Author
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Jan-Åke Gustafsson, Ivo Lambrichts, Elien Wouters, Jeroen F. J. Bogie, Aida Garcia Corrales, Pascal Gervois, Noam Zelcer, Esther Wolfs, Jo Mailleux, Alan T. Remaley, Tess Dierckx, Jana Van Broeckhoven, Shane R. Ellis, Jerome J. A. Hendriks, Johannes V. Swinnen, Monique T. Mulder, Jonas Dehairs, James M. Ntambi, Sam Vanherle, Andrew P. Bowman, Elien Grajchen, Mansour Haidar, Medical Biochemistry, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, AGEM - Endocrinology, metabolism and nutrition, Internal Medicine, Imaging Mass Spectrometry (IMS), and RS: M4I - Imaging Mass Spectrometry (IMS)
- Subjects
0301 basic medicine ,ELECTROSPRAY-IONIZATION ,CHOLESTEROL EFFLUX ,Phagocyte ,FOAM CELLS ,REMYELINATION ,Myelin ,0302 clinical medicine ,Neuroinflammation ,MYELIN PHAGOCYTOSIS ,Immunology and Allergy ,Myelin Sheath ,GENE-EXPRESSION ,Phagocytes ,biology ,Microglia ,Chemistry ,Fatty Acids ,Brain ,DEFICIENCY PROTECTS ,Endocytosis ,Cell biology ,Protein Kinase C-delta ,Cholesterol ,Phenotype ,medicine.anatomical_structure ,lipids (amino acids, peptides, and proteins) ,FATTY-ACIDS ,Stearoyl-CoA Desaturase ,Intracellular ,ATP Binding Cassette Transporter 1 ,Innate Immunity and Inflammation ,Immunology ,Article ,Cell Line ,03 medical and health sciences ,medicine ,Animals ,Humans ,STIMULATED MACROPHAGES ,Remyelination ,Inflammation ,Macrophages ,MICE ,Metabolism ,030104 developmental biology ,ABCA1 ,biology.protein ,Stearoyl-CoA desaturase-1 ,030217 neurology & neurosurgery ,Ex vivo - Abstract
In this study, Bogie, Grajchen et al. show that monounsaturated fatty acids formed by stearoyl-CoA desaturase-1 impair the reparative features of macrophages and microglia in demyelinating disorders by reducing their lipid efflux capacity., 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.
- Published
- 2020