Untargeted plasma metabolomics identifies endogenous metabolite with drug-like properties in chronic animal model of multiple sclerosis

Laila M. Poisson, Hamid Suhail, Jaspreet Singh, Indrani Datta, Aleksandar Deni, Krzysztof Labuzek, Nasrul Hoda, Ashray Shankar, Ashok Kumar, Mirela Cerghet, Stanton Elias, Robert P. Mohney, Moses Rodriguez, Ramandeep Rattan, Ashutosh K. Mangalam, Shailendra Giri

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

We performed untargeted metabolomics in plasma of B6 mice with experimental autoimmune encephalitis (EAE) at the chronic phase of the disease in search of an altered metabolic pathway(s). Of 324 metabolites measured, 100 metabolites that mapped to various pathways (mainly lipids) linked to mitochondrial function, inflammation, and membrane stability were observed to be significantly altered between EAE and control (p > 0.05, false discovery rate >0.10). Bioinformatics analysis revealed six metabolic pathways being impacted and altered in EAE, including <-linolenic acid and linoleic acid metabolism (PUFA). The metabolites of PUFAs, includingω-3 andω-6 fatty acids, are commonly decreased in mouse models of multiple sclerosis (MS) and in patients with MS. Daily oral administration of resolvin D1, a downstream metabolite ofω-3, decreased disease progression by suppressing autoreactive T cells and inducing an M2 phenotype of monocytes/macrophages and resident brain microglial cells. This study provides a proof of principle for the application of metabolomics to identify an endogenous metabolite(s) possessing drug-like properties, which is assessed for therapy in preclinical mouse models of MS.

Original languageEnglish (US)
Pages (from-to)30697-30712
Number of pages16
JournalJournal of Biological Chemistry
Volume290
Issue number52
DOIs
StatePublished - Dec 25 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Poisson, L. M., Suhail, H., Singh, J., Datta, I., Deni, A., Labuzek, K., Hoda, N., Shankar, A., Kumar, A., Cerghet, M., Elias, S., Mohney, R. P., Rodriguez, M., Rattan, R., Mangalam, A. K., & Giri, S. (2015). Untargeted plasma metabolomics identifies endogenous metabolite with drug-like properties in chronic animal model of multiple sclerosis. Journal of Biological Chemistry, 290(52), 30697-30712. https://doi.org/10.1074/jbc.M115.679068