Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex illness which disproportionally affects females. This illness is associated with immune and metabolic perturbations that may be influenced by lipid metabolism. We therefore hypothesized that plasma lipids from ME/CFS patients will provide a unique biomarker signature of disturbances in immune, inflammation and metabolic processes associated with ME/CFS. Lipidomic analyses were performed on plasma from a cohort of 50 ME/CFS patients and 50 controls (50% males and similar age and ethnicity per group). Analyses were conducted with nano-flow liquid chromatography (nLC) and high-performance liquid chromatography (HPLC) systems coupled with a high mass accuracy ORBITRAP mass spectrometer, allowing detection of plasma lipid concentration ranges over three orders of magnitude. We examined plasma phospholipids (PL), neutral lipids (NL) and bioactive lipids in ME/CFS patients and controls and examined the influence of sex on the relationship between lipids and ME/CFS diagnosis. Among females, levels of total phosphatidylethanolamine (PE), omega-6 arachidonic acid-containing PE, and total hexosylceramides (HexCer) were significantly decreased in ME/CFS compared to controls. In males, levels of total HexCer, monounsaturated PE, phosphatidylinositol (PI), and saturated triglycerides (TG) were increased in ME/CFS patients compared to controls. Additionally, omega-6 linoleic acid-derived oxylipins were significantly increased in male ME/CFS patients versus male controls. Principal component analysis (PCA) identified three major components containing mostly PC and a few PE, PI and SM species—all of which were negatively associated with headache and fatigue severity, irrespective of sex. Correlations of oxylipins, ethanolamides and ME/CFS symptom severity showed that lower concentrations of these lipids corresponded with an increase in the severity of headaches, fatigue and cognitive difficulties and that this association was influenced by sex. The observed sex-specific pattern of dysregulated PL, NL, HexCer and oxylipins in ME/CFS patients suggests a possible role of these lipids in promoting immune dysfunction and inflammation which may be among the underlying factors driving the clinical presentation of fatigue, chronic pain, and cognitive difficulties in ill patients. Further evaluation of lipid metabolism pathways is warranted to better understand ME/CFS pathogenesis.

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ME/CFS 患者的性别特异性血脂谱及其与疼痛、疲劳和认知症状的关联

肌痛性脑脊髓炎/慢性疲劳综合征 (ME/CFS) 是一种复杂的疾病，对女性的影响不成比例。这种疾病与可能受脂质代谢影响的免疫和代谢紊乱有关。因此，我们假设来自 ME/CFS 患者的血浆脂质将提供与 ME/CFS 相关的免疫、炎症和代谢过程紊乱的独特生物标志物特征。对来自 50 名 ME/CFS 患者和 50 名对照（每组 50% 的男性和相似的年龄和种族）的队列的血浆进行脂质组学分析。使用纳流液相色谱 (nLC) 和高效液相色谱 (HPLC) 系统与高质量准确度 ORBITRAP 质谱仪进行分析，允许检测超过三个数量级的血浆脂质浓度范围。我们检查了 ME/CFS 患者和对照的血浆磷脂 (PL)、中性脂质 (NL) 和生物活性脂质，并检查了性别对脂质与 ME/CFS 诊断之间关系的影响。在雌性中，与对照组相比，ME/CFS 中总磷脂酰乙醇胺 (PE)、含有 omega-6 花生四烯酸的 PE 和总己糖基神经酰胺 (HexCer) 的水平显着降低。在男性中，与对照组相比，ME/CFS 患者的总 HexCer、单不饱和 PE、磷脂酰肌醇 (PI) 和饱和甘油三酯 (TG) 的水平增加。此外，与男性对照相比，男性 ME/CFS 患者的 omega-6 亚油酸衍生的oxylipins 显着增加。主成分分析 (PCA) 确定了三个主要成分，主要包含 PC 和少量 PE，PI 和 SM 物种——所有这些都与头痛和疲劳严重程度呈负相关，无论性别如何。oxylipins、乙醇酰胺和 ME/CFS 症状严重程度的相关性表明，这些脂质浓度越低，头痛、疲劳和认知困难的严重程度越高，并且这种关联受性别影响。在 ME/CFS 患者中观察到的 PL、NL、HexCer 和 oxylipins 失调的性别特异性模式表明这些脂质可能在促进免疫功能障碍和炎症方面发挥作用，这可能是导致疲劳、慢性疼痛、和病人的认知困难。有必要对脂质代谢途径进行进一步评估，以更好地了解 ME/CFS 发病机制。不分性别。oxylipins、乙醇酰胺和 ME/CFS 症状严重程度的相关性表明，这些脂质浓度越低，头痛、疲劳和认知困难的严重程度越高，并且这种关联受性别影响。在 ME/CFS 患者中观察到的 PL、NL、HexCer 和 oxylipins 失调的性别特异性模式表明这些脂质可能在促进免疫功能障碍和炎症方面发挥作用，这可能是导致疲劳、慢性疼痛、和病人的认知困难。有必要对脂质代谢途径进行进一步评估，以更好地了解 ME/CFS 发病机制。不分性别。oxylipins、乙醇酰胺和 ME/CFS 症状严重程度的相关性表明，这些脂质浓度越低，头痛、疲劳和认知困难的严重程度越高，并且这种关联受性别影响。在 ME/CFS 患者中观察到的 PL、NL、HexCer 和 oxylipins 失调的性别特异性模式表明这些脂质可能在促进免疫功能障碍和炎症方面发挥作用，这可能是导致疲劳、慢性疼痛、和病人的认知困难。有必要对脂质代谢途径进行进一步评估，以更好地了解 ME/CFS 发病机制。乙醇酰胺和 ME/CFS 症状严重程度表明，这些脂质的浓度较低与头痛、疲劳和认知困难的严重程度增加相对应，并且这种关联受性别影响。在 ME/CFS 患者中观察到的 PL、NL、HexCer 和 oxylipins 失调的性别特异性模式表明这些脂质可能在促进免疫功能障碍和炎症方面发挥作用，这可能是导致疲劳、慢性疼痛、和病人的认知困难。有必要对脂质代谢途径进行进一步评估，以更好地了解 ME/CFS 发病机制。乙醇酰胺和 ME/CFS 症状严重程度表明，这些脂质的浓度较低与头痛、疲劳和认知困难的严重程度增加相对应，并且这种关联受性别影响。在 ME/CFS 患者中观察到的 PL、NL、HexCer 和 oxylipins 失调的性别特异性模式表明这些脂质可能在促进免疫功能障碍和炎症方面发挥作用，这可能是导致疲劳、慢性疼痛、和病人的认知困难。有必要对脂质代谢途径进行进一步评估，以更好地了解 ME/CFS 发病机制。在 ME/CFS 患者中观察到的 PL、NL、HexCer 和 oxylipins 失调的性别特异性模式表明这些脂质可能在促进免疫功能障碍和炎症方面发挥作用，这可能是导致疲劳、慢性疼痛、和病人的认知困难。有必要对脂质代谢途径进行进一步评估，以更好地了解 ME/CFS 发病机制。在 ME/CFS 患者中观察到的 PL、NL、HexCer 和 oxylipins 失调的性别特异性模式表明这些脂质可能在促进免疫功能障碍和炎症方面发挥作用，这可能是导致疲劳、慢性疼痛、和病人的认知困难。有必要对脂质代谢途径进行进一步评估，以更好地了解 ME/CFS 发病机制。