Fig. 4

Attempts of targeting FAs and FA metabolism in MS animal models. A blockage of FAs chaperones or critical FAS enzymes, including fatty acid binding protein 4/5 (FABP4/5), FABP5/7, fatty acid synthase (FASN) and ACC1, by inducing FAO in peripheral immune system, manages to restore the proper balance of Treg–Th1/17 axis, mitigating EAE severity. SCFAs and omega-3 PUFAs including DHA or EPA treatments are also able to reduce EAE clinical score by manipulating CD4⁺T cells differentiation and subtype function. The blockage of CD5L, an inhibitor of FASN function, serves to increase SFA/PUFA ratio in Th17 cells, favoring a more pathogenic phenotype, therefore, aggravating EAE symptoms. Methyl acetate treatment by reducing Th1, Th17 chemotaxis and CNS infiltration mitigates EAE. Valproic acid (VPA) supplementation alleviates EAE by promoting T cells apoptosis. Valeric acid supplementation boosts Breg function which leads to EAE remission. In CNS pathogenic state, omega-3 PUFAs and butyrate either by increasing anti-inflammatory bio-mediators or by directly supporting oligodendrocyte precursor cell (OPC) differentiation, alleviate cuprizone-induced demyelination. Oleic acid supplementation relieves EAE symptoms by reducing oxidative stress as the decrease of GSH/GSSG ratio. VPA mitigates EAE by reducing retinal ganglion cells (RGC) apoptosis and by recruiting neural stem or progenitor cells (NSC, NPC). Critical FAO enzyme CPT1 inhibitor and VPA administration alleviate EAE demyelination by reducing FA loss while boosting FA and cholesterol biosynthesis. EAE experimental autoimmune encephalomyelitis, PUFA poly-unsaturated fatty acid, SFA saturated fatty acid