Shen Qing, Otoki Yurika, Sobel Raymond A, Nagra Rashed M, Taha Ameer Y
Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, Davis, CA 95616, USA.
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.
Mult Scler Relat Disord. 2022 Dec;68:104236. doi: 10.1016/j.msard.2022.104236. Epub 2022 Oct 9.
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.
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.
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.
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.
多发性硬化症（MS）中未解决的炎症与进行性脱髓鞘和症状恶化有关。在大脑中，炎症和消退途径均由游离脂质介质（即氧化脂质）介导，这些介质可源自酯化氧化脂质的酶促水解。目前尚不清楚MS患者死后大脑中游离脂质介质从酯化池中周转的过程是否存在紊乱。我们假设，由于游离促消退脂质介质从酯化脂质周转过程中的紊乱，MS患者的消退途径受损。目的是对MS患者和未受影响的对照参与者死后前额叶皮质中的游离和酯化氧化脂质进行表征。
从10名MS参与者和5名未受影响的对照者的前额叶皮质中提取游离、中性脂质和磷脂池中的氧化脂质，通过固相萃取柱进行分离，并通过超高压液相色谱-串联质谱法进行定量。对照组和MS组之间的显著差异通过未配对t检验确定，并对每个脂质池中的氧化脂质应用Benjamini和Hochberg错误发现率校正（10%）。
与对照参与者相比，MS患者死后前额叶皮质中中性脂质内7种酯化促消退脂肪酸环氧化物的浓度显著高出126%-285%。酯化亚油酸衍生的促炎环氧化物9(10)-环氧-十八碳烯酸的浓度在MS患者中比对照组高出206%。在游离或磷脂结合的氧化脂质中未观察到显著变化。
在MS中，几种促消退脂质介质被困在前额叶皮质中性脂质中，可能会限制它们以游离生物活性形式的供应和可用性。这可能解释了为什么MS患者的炎症消退受损。
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