Dimethyl fumarate treatment induces lipid metabolism alterations that are linked to immunological changes

Research output: Contribution to journalArticle

Abstract

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 CD8+ 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.

Original languageEnglish (US)
JournalAnnals of Clinical and Translational Neurology
DOIs
StateAccepted/In press - Jan 1 2018

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Lipid Metabolism
Metabolomics
Fatty Acids
Lymphocyte Count
Plasmalogens
Lysophospholipids
Therapeutics
Lymphopenia
T-Lymphocyte Subsets
Unsaturated Fatty Acids
Phospholipids
Dimethyl Fumarate

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

@article{a693bf5128084d3eb00286ff6b6b8877,
title = "Dimethyl fumarate treatment induces lipid metabolism alterations that are linked to immunological changes",
abstract = "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 CD8+ 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.",
author = "Pavan Bhargava and Kathryn Fitzgerald and Venkata, {Swarajya L.V.} and Smith, {Matthew D.} and Michael Kornberg and Mowry, {Ellen Mahar} and Norman Haughey and Peter Calabresi",
year = "2018",
month = "1",
day = "1",
doi = "10.1002/acn3.676",
language = "English (US)",
journal = "Annals of Clinical and Translational Neurology",
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T1 - Dimethyl fumarate treatment induces lipid metabolism alterations that are linked to immunological changes

AU - Bhargava, Pavan

AU - Fitzgerald, Kathryn

AU - Venkata, Swarajya L.V.

AU - Smith, Matthew D.

AU - Kornberg, Michael

AU - Mowry, Ellen Mahar

AU - Haughey, Norman

AU - Calabresi, Peter

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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 CD8+ 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.

AB - 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 CD8+ 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.

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