Open AccessDimethyl fumarate treatment induces lipid metabolism alterations that are linked to immunological changes
Author(s) -
Bhargava Pavan,
Fitzgerald Kathryn C.,
Venkata Swarajya L. V.,
Smith Matthew D.,
Kornberg Michael D.,
Mowry Ellen M.,
Haughey Norman J.,
Calabresi Peter A.
Publication year - 2019
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.676
Subject(s) - medicine , dimethyl fumarate , lipid metabolism , metabolism , pharmacology , immunology , multiple sclerosis
Objective Identify metabolic changes produced by dimethyl fumarate ( DMF ) treatment and link them to immunological effects. Methods We enrolled 18 MS patients and obtained blood prior to DMF and 6 months postinitiation. We also enrolled 18 healthy controls for comparison. We performed global metabolomics on plasma and used weighted correlation network analysis ( WGCNA ) to identify modules of correlated metabolites. We identified modules that changed with treatment, followed by targeted metabolomics to corroborate changes identified in global analyses. We correlated changes in metabolite modules and individual metabolites with changes in immunological parameters. Results We identified alterations in lipid metabolism after DMF treatment – increases in two modules (phospholipids, lysophospholipids and plasmalogens) and reduction in one module (saturated and poly‐unsaturated fatty acids) eigen‐metabolite values (all P < 0.05). Change in the fatty acid module was greater in participants who developed lymphopenia and was strongly associated with both reduction in absolute lymphocyte counts ( r = 0.65; P = 0.005) and change in CD 8+ T cell subsets. We also noted significant correlation of change in lymphocyte counts with multiple fatty acid levels (measured by targeted or untargeted methods). Interpretation This study demonstrates that DMF treatment alters lipid metabolism and that changes in fatty acid levels are related to DMF ‐induced immunological changes.