Evidence of increased sequestration of pro-resolving lipid mediators within brain esterified lipid pools of multiple sclerosis patients

Qing Shen; Yurika Otoki; Raymond A Sobel; Rashed M Nagra; Ameer Y Taha

doi:10.1016/j.msard.2022.104236

Evidence of increased sequestration of pro-resolving lipid mediators within brain esterified lipid pools of multiple sclerosis patients

Mult Scler Relat Disord. 2022 Dec:68:104236. doi: 10.1016/j.msard.2022.104236. Epub 2022 Oct 9.

Authors

Qing Shen¹, Yurika Otoki², Raymond A Sobel³, Rashed M Nagra⁴, Ameer Y Taha⁵

Affiliations

¹ Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, Davis, CA 95616, USA.
² Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, Davis, CA 95616, USA; Food Function Analysis Laboratory, Graduate School of Agricultural Science, Tohoku University, Miyagi, Japan.
³ Veterans Affairs Health Care System, Palo Alto, CA 94304, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁴ Neurology Research, West Los Angeles VA Medical Center, Los Angeles, CA 90073, USA.
⁵ Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, Davis, CA 95616, USA; Center for Neuroscience, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA; West Coast Metabolomics Center, Genome Center, University of California-Davis, Davis, CA, USA. Electronic address: ataha@ucdavis.edu.

PMID: 36308971
DOI: 10.1016/j.msard.2022.104236

Abstract

Background: Unresolved inflammation in multiple sclerosis (MS) is associated with progressive demyelination and symptom worsening. In the brain, both inflammation and resolution pathways are mediated by free lipid mediators (i.e., oxylipins) that can be derived from the enzymatic hydrolysis of esterified oxylipins . It is not known whether disturbances in the turnover of free lipid mediators from esterified pools exist in postmortem brain of MS patients. We hypothesized that resolution pathways are impaired in MS patients because of disturbances in the turnover of free pro-resolving lipid mediators from esterified lipids. The objective was to characterize free and esterified oxylipins in postmortem prefrontal cortex of MS and unaffected control participants.

Methods: Oxylipins in free, neutral lipid and phospholipid pools were extracted from prefrontal cortex of 10 MS participants and 5 unaffected controls, separated by solid phase extraction columns, and quantified by ultra-high-pressure liquid chromatography-tandem mass spectrometry. Significant differences between the control and MS groups were determined by an unpaired t-test with Benjamini and Hochberg False Discovery Rate correction (10%) applied to oxylipins within each lipid pool.

Results: The concentration of 7 esterified pro-resolving fatty acid epoxides within neutral lipids were significantly higher by 126%-285% in postmortem prefrontal cortex of MS compared to control participants. The concentration of esterified linoleic acid-derived 9(10)-epoxy-octadecenoic acid, a pro-inflammatory epoxide, was higher by 206% in MS compared to controls. No significant changes were observed in free or phospholipid-bound oxylipins.

Conclusion: In MS, several pro-resolving lipid mediators are trapped within prefrontal cortex neutral lipids, potentially limiting their supply and availability in the free bioactive form. This may explain why inflammation resolution is impaired in MS patients.

Keywords: Inflammation; Lipid mediators; Multiple sclerosis; Neutral lipids; Oxylipins; Post mortem.

MeSH terms

Brain
Epoxy Compounds
Humans
Multiple Sclerosis*
Oxylipins / analysis
Phospholipids
Tandem Mass Spectrometry* / methods

Substances

Oxylipins
Phospholipids
Epoxy Compounds