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 Denic; Krzysztof Labuzek; Md Nasrul Hoda; Ashray Shankar; Ashok Kumar; Mirela Cerghet; Stanton Elias; Robert P Mohney; Moses Rodriguez; Ramandeep Rattan; Ashutosh K Mangalam; Shailendra Giri

doi:10.1074/jbc.M115.679068

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Untargeted Plasma Metabolomics Identifies Endogenous Metabolite with Drug-like Properties in Chronic Animal Model of Multiple Sclerosis

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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 Denic, Krzysztof Labuzek, Md Nasrul Hoda, Ashray Shankar, Ashok Kumar, Mirela Cerghet, …

The Journal of biological chemistry, Vol.290(52), pp.30697-30712

12/25/2015

DOI: 10.1074/jbc.M115.679068

PMCID: PMC4692201

PMID: 26546682

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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 α-linolenic acid and linoleic acid metabolism (PUFA). The metabolites of PUFAs, including ω-3 and ω-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 of ω-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.

Metabolomics

Encephalomyelitis, Autoimmune, Experimental - metabolism

Humans

Fatty Acids, Unsaturated - metabolism

Plasma - metabolism

Animals

Fatty Acids, Unsaturated - chemistry

Metabolic Networks and Pathways

Plasma - chemistry

Female

Mice

Disease Models, Animal

Multiple Sclerosis - metabolism

Details

Title: Subtitle: Untargeted Plasma Metabolomics Identifies Endogenous Metabolite with Drug-like Properties in Chronic Animal Model of Multiple Sclerosis
Creators: Laila M Poisson - From the Center for Bioinformatics and Departments of Public Health Sciences and
Hamid Suhail - Henry Ford Health System
Jaspreet Singh - Henry Ford Health System
Indrani Datta - Henry Ford Health System
Aleksandar Denic - the Departments of Neurology and
Krzysztof Labuzek - Medical University of Silesia
Md Nasrul Hoda - Augusta University
Ashray Shankar - Henry Ford Health System
Ashok Kumar - University of Iowa
Mirela Cerghet - Henry Ford Health System
Stanton Elias - Henry Ford Hospital
Robert P Mohney - Metabolon (United States)
Moses Rodriguez - Mayo Clinic
Ramandeep Rattan - Henry Ford Health System
Ashutosh K Mangalam - the Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242
Shailendra Giri - Henry Ford Health System
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.290(52), pp.30697-30712
DOI: 10.1074/jbc.M115.679068
PMID: 26546682
PMCID: PMC4692201
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: R01 GM092993 / NIGMS NIH HHS R01GM092993 / NIGMS NIH HHS
Language: English
Date published: 12/25/2015
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9983905648102771

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