Mitochondrial impairment but not peripheral inflammation predicts greater Gulf War illness severity.
Mitochondrial impairment but not peripheral inflammation predicts greater Gulf War illness severity.
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线粒体损伤，但没有外周炎症预测海湾战争疾病的严重程度更大。
DOI：
10.1038/s41598-023-35896-w
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发表时间：
2023-07-12
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
海湾战争病（GWI）是环境引发的慢性多症状疾病的一个重要范例，也是加速衰老的潜在模型。炎症是GWI的主要假设机制，线粒体损伤也被提出。没有研究直接评估GWI退伍军人（VGWI）肌肉活检的线粒体呼吸链功能（MRCF）。我们招募了42名参与者，其中一半是VGWI， 36名成功获得活检材料。以葡萄糖为燃料源的复合物I和II氧化磷酸化（CI&CIIOXPHOS）为指标的MRCF损伤与联合样本中20种症状中的17种在预测方向上显著或临界相关。无论是否调整hsCRP，较低的ci和ciioxphos分别显著预测联合样本和VGWI的GWI严重程度。在VGWI中，较高的hscrp（外周炎症）与较低的mrcf（特别是脂肪酸氧化（FAO）指数）密切相关，但在对照组中没有。尽管如此，更大的mrcf损伤预示着更严重的GWI症状和严重程度，而更大的炎症却没有。令人惊讶的是，经MRCF调整后，较高的hsCRP选择性地显著预测VGWI较轻的症状严重程度。研究结果与一种假设相一致，即GWI中观察到的炎症增加是由fao缺陷诱导的线粒体凋亡驱动的。总之，线粒体功能受损——而非外周炎症——预示着更严重的GWI症状和严重程度。
Gulf War illness (GWI) is an important exemplar of environmentally-triggered chronic multisymptom illness, and a potential model for accelerated aging. Inflammation is the main hypothesized mechanism for GWI, with mitochondrial impairment also proposed. No study has directly assessed mitochondrial respiratory chain function (MRCF) on muscle biopsy in veterans with GWI (VGWI). We recruited 42 participants, half VGWI, with biopsy material successfully secured in 36. Impaired MRCF indexed by complex I and II oxidative phosphorylation with glucose as a fuel source (CI&CIIOXPHOS) related significantly or borderline significantly in the predicted direction to 17 of 20 symptoms in the combined sample. Lower CI&CIIOXPHOS significantly predicted GWI severity in the combined sample and in VGWI separately, with or without adjustment for hsCRP. Higher-hsCRP (peripheral inflammation) related strongly to lower-MRCF (particularly fatty acid oxidation (FAO) indices) in VGWI, but not in controls. Despite this, whereas greater MRCF-impairment predicted greater GWI symptoms and severity, greater inflammation did not. Surprisingly, adjusted for MRCF, higher hsCRP significantly predicted lesser symptom severity in VGWI selectively. Findings comport with a hypothesis in which the increased inflammation observed in GWI is driven by FAO-defect-induced mitochondrial apoptosis. In conclusion, impaired mitochondrial function—but not peripheral inflammation—predicts greater GWI symptoms and severity.
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影响因子：
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