Associations between TCA cycle plasma metabolites and fatigue in black females with systemic lupus erythematosus: An untargeted metabolomics pilot study.

IF 1.9 4区 医学 Q3 RHEUMATOLOGY
Lupus Pub Date : 2024-08-01 Epub Date: 2024-06-17 DOI:10.1177/09612033241260334
Laura P Kimble, Arezou Khosroshahi, Glenna S Brewster, Sandra B Dunbar, Dylan Ryan, Nicole Carlson, Ron Eldridge, Madelyn Houser, Elizabeth Corwin
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引用次数: 0

Abstract

Objective: In this pilot study, we used untargeted metabolomics to identify biochemical mechanisms or biomarkers potentially underlying SLE-related fatigue.

Methods: Metabolon conducted untargeted metabolomic plasma profiling using ultrahigh performance liquid chromatography/tandem mass spectrometry on plasma samples of 23 Black females with systemic lupus erythematosus (SLE) and 21 no SLE controls. Fatigue phenotypes of general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation were measured with the reliable and valid Multidimensional Fatigue Inventory (MFI).

Results: A total of 290 metabolites were significantly different between the SLE and no SLE groups, encompassing metabolites related to glycolysis, TCA cycle activity, heme catabolism, branched chain amino acids, fatty acid metabolism, and steroids. Within the SLE group, controlling for age and co-morbidities, TCA cycle metabolites of alpha-ketoglutarate (AKG) and succinate were statistically significantly associated (p < .05) with physical and general fatigue.

Conclusion: While pervasive perturbations in the entire TCA cycle have been implicated as a potential mechanism for fatigue, our results suggest individual metabolites of AKG and succinate may be potential biomarkers or targets of intervention for fatigue symptom management in SLE. Additionally, perturbations in heme metabolism in the SLE group provide additional insights into mechanisms that promote systemic inflammation.

患有系统性红斑狼疮的黑人女性的 TCA 循环血浆代谢物与疲劳之间的关系:一项非靶向代谢组学试验研究。
目的在这项试验性研究中,我们利用非靶向代谢组学来确定可能导致系统性红斑狼疮相关疲劳的生化机制或生物标志物:Metabolon公司使用超高效液相色谱/串联质谱法对23名患有系统性红斑狼疮(SLE)的黑人女性和21名未患系统性红斑狼疮的对照者的血浆样本进行了非靶向代谢组学分析。采用可靠有效的多维疲劳量表(MFI)测量了全身疲劳、身体疲劳、精神疲劳、活动减少和动力减退等疲劳表型:结果:系统性红斑狼疮组和非系统性红斑狼疮组之间共有 290 种代谢物存在显著差异,包括与糖酵解、TCA 循环活性、血红素分解、支链氨基酸、脂肪酸代谢和类固醇有关的代谢物。在系统性红斑狼疮组中,在控制年龄和合并疾病的情况下,TCA循环代谢物α-酮戊二酸(AKG)和琥珀酸与体力和全身疲劳有显著的统计学相关性(p < .05):结论:虽然整个TCA循环的普遍紊乱被认为是疲劳的潜在机制,但我们的研究结果表明,AKG和琥珀酸的单个代谢物可能是潜在的生物标志物,也可能是干预系统性红斑狼疮疲劳症状的目标。此外,系统性红斑狼疮患者体内血红素代谢的紊乱也让我们对促进全身炎症的机制有了更多的了解。
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来源期刊
Lupus
Lupus 医学-风湿病学
CiteScore
4.20
自引率
11.50%
发文量
225
审稿时长
1 months
期刊介绍: The only fully peer reviewed international journal devoted exclusively to lupus (and related disease) research. Lupus includes the most promising new clinical and laboratory-based studies from leading specialists in all lupus-related disciplines. Invaluable reading, with extended coverage, lupus-related disciplines include: Rheumatology, Dermatology, Immunology, Obstetrics, Psychiatry and Cardiovascular Research…
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