Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Centre for Human Metabolomics, North-West University, Potchefstroom, South Africa.
Sci Rep. 2020 Oct 26;10(1):18232. doi: 10.1038/s41598-020-75406-w.
Chronic fatigue syndrome (CFS) patients often suffer from severe muscle pain and an inability to exercise due to muscle fatigue. It has previously been shown that CFS skeletal muscle cells have lower levels of ATP and have AMP-activated protein kinase dysfunction. This study outlines experiments looking at the utilisation of different substrates by skeletal muscle cells from CFS patients (n = 9) and healthy controls (n = 11) using extracellular flux analysis. Results show that CFS skeletal muscle cells are unable to utilise glucose to the same extent as healthy control cells. CFS skeletal muscle cells were shown to oxidise galactose and fatty acids normally, indicating that the bioenergetic dysfunction lies upstream of the TCA cycle. The dysfunction in glucose oxidation is similar to what has previously been shown in blood cells from CFS patients. The consistency of cellular bioenergetic dysfunction in different cell types supports the hypothesis that CFS is a systemic disease. The retention of bioenergetic defects in cultured cells indicates that there is a genetic or epigenetic component to the disease. This is the first study to use cells derived from skeletal muscle biopsies in CFS patients and healthy controls to look at cellular bioenergetic function in whole cells.
慢性疲劳综合征（CFS）患者常因肌肉疲劳而出现严重的肌肉疼痛和运动能力下降。先前的研究表明，CFS 骨骼肌细胞中的 ATP 水平较低，并且 AMP 激活的蛋白激酶功能异常。本研究通过细胞外通量分析，概述了观察 CFS 患者（n=9）和健康对照者（n=11）的骨骼肌细胞利用不同底物的实验。结果表明，CFS 骨骼肌细胞利用葡萄糖的能力不如健康对照组细胞。研究表明，CFS 骨骼肌细胞可以正常氧化半乳糖和脂肪酸，这表明生物能量功能障碍发生在三羧酸循环之前。葡萄糖氧化的功能障碍与之前在 CFS 患者的血细胞中观察到的情况相似。不同细胞类型中细胞生物能量功能障碍的一致性支持 CFS 是一种全身性疾病的假说。在培养细胞中保留生物能量缺陷表明该疾病存在遗传或表观遗传成分。这是首次使用源自 CFS 患者和健康对照者的骨骼肌活检细胞来研究全细胞的细胞生物能量功能。
