title: Inhibition of fatty acid metabolism ameliorates disease activity in an animal model of multiple sclerosis.
abstract: Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system and a leading cause of neurological disability. The complex immunopathology and variable disease course of multiple sclerosis have limited effective treatment of all patients. Altering the metabolism of immune cells may be an attractive strategy to modify their function during autoimmunity. We examined the effect of inhibiting fatty acid metabolism in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Mice treated with an inhibitor of carnitine palmitoyltransferase 1 (CPT-1), the rate-limiting enzyme in the beta-oxidation of fatty acids, showed a reduction in disease severity as well as less inflammation and demyelination. Inhibition of CPT-1 in encephalitogenic T-cells resulted in increased apoptosis and reduced inflammatory cytokine production. These results suggest that disruption of fatty acid metabolism promotes downregulation of inflammation in the CNS and that this metabolic pathway is a potential therapeutic target for multiple sclerosis.
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California , San Diego, 9500 Gilman Drive, La Jolla, California. 92093. USA.
authors.forename: Leah P
authors.initials: LP
authors.lastname: Shriver
authors.forename: Marianne
authors.initials: M
authors.lastname: Manchester
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000503:physiopathology; D005227:Fatty Acids / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000503:physiopathology; D010084:Oxidation-Reduction; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D005227:Fatty Acids