Cpt1a-mutated mice have changes in serum metabolites and high fat diet affects disease progression in EAE mouse model, and gene expression in spinal cord. (a) Glucose level in serum from Cpt1a-mutated male mice (n = 12) and WT mice (n = 15). (b) LDL level in serum from Cpt1a-mutated male mice (n = 6) and WT mice (n = 5). (c) HDL level in serum from Cpt1a-mutated male mice (n = 6) and WT mice (n = 5). (d) LDL/HDL ratio in serum from Cpt1a-mutated male mice (n = 6) and WT mice (n = 5). (e) Mean fold gene expression change of Cpt1a in spinal cord of female WT- (n = 3) and Cpt1a-mutated mice (n = 3). (f) Experimental setup for the high fat diet Cpt1a-EAE and WT-EAE study comparing the effect of HFD on EAE disease progression. (g) Efficacy of high-fat diet on EAE disease severity of WT-EAE (n = 5) and Cpt1a-EAE (n = 6) mice from day 10 to day 24. (h) Mean fold gene expression change of Pgc1α in spinal cord of female WT- (n = 3) and Cpt1a-mutated mice (n = 3). (i) Mean fold gene expression change of Nrf2 in spinal cord of female WT-ND (n = 4) and WT-HFD mice (n = 4). Asterisks indicate the level of statistical significance (*p < 0.05). Abbreviations: Cpt1a, carnitine palmitoyl transferase 1a with a p479l mutation; ND, normal diet, HFD, high fat diet. E, etomoxir; P, placebo; EAE, experimental autoimmune encephalomyelitis; MOG, Myelin-oligodendrocyte glycoprotein35–55 (MOG35–55), CFA, Complete Freund's Adjuvant; S.c., Subcutaneous; I.p., Intraperitoneal; Inj., Injection; WT, wild type. SEM: standard error of the mean. We acknowledge Servier Medical Art for the mouse illustration, which can be found at: https://smart.servier.com/. License; https://creativecommons.org/licenses/by/3.0/. No changes were made to the drawing.