Altered skeletal muscle metabolic pathways, age, systemic inflammation, and low cardiorespiratory fitness associate with improvements in disease activity following high-intensity interval training in persons with rheumatoid arthritis.
Altered skeletal muscle metabolic pathways, age, systemic inflammation, and low cardiorespiratory fitness associate with improvements in disease activity following high-intensity interval training in persons with rheumatoid arthritis.
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DOI：
10.1186/s13075-021-02570-3
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发表时间：
2021-07-10
影响因子：
4.9
通讯作者：
Huffman KM
中科院分区：
文献类型：
--
作者：
Andonian BJ;Johannemann A;Hubal MJ;Pober DM;Koss A;Kraus WE;Bartlett DB;Huffman KM
运动训练，包括高强度间歇训练（HIIT），可通过尚不清楚的机制改善类风湿性关节炎（RA）炎症性疾病的活动。由于运动需要骨骼肌，因此骨骼肌分子途径可能有所贡献。本研究的目的是确定骨骼肌分子通路、RA 疾病活动性和 HIIT 后 RA 疾病活动性改善之间的联系。在两个单独的已确诊、血清反应阳性和/或糜烂性 RA 患者队列中进行了 RA 疾病活动评估和股外侧肌活检。在 HIIT 10 周之前和之后，还对横断面队列和纵向组进行了身体成分和客观身体活动评估。基线临床评估和肌肉 RNA 基因表达与 28 个关节的 RA 疾病活动评分 (DAS-28) 以及 HIIT 后 DAS-28 的改善相关。使用协方差分析和生物途径分析来评估 HIIT 引起的骨骼肌基因表达变化。 RA 炎症性疾病活动性与较大量的肌内肥胖和较少剧烈的有氧运动相关（均 p < 0.05）。 HIIT 诱导的疾病活动改善在年龄较大、红细胞沉降率升高、心肺健康水平较低以及骨骼肌分子谱表明代谢途径发生改变的患者中最为明显（所有患者的 p < 0.05）。具体来说，疾病活动的改善与具有细胞功能的 RA 骨骼肌基因的基线表达相关，以（1）增加氨基酸分解代谢和相互转化（GLDC、BCKDHB、AASS、PYCR、RPL15），（2）增加糖酵解乳酸的产生（AGL、PDK2、LDHB、HIF1A），以及（3）通过改变β-氧化（PXMP2、ACSS2）、TCA 循环通量来减少氧化代谢（OGDH、SUCLA2、MDH1B）和电子传递链复合体 I 功能（NDUFV3）。由于基线时多个 GCS 基因上调，肌肉线粒体甘氨酸裂解系统 (GCS) 被认为与 RA 疾病活动改善密切相关，而 GLDC 在 HIIT 后显着下调。在缺乏体力活动的情况下，RA 炎症性疾病活动与骨骼肌代谢的转录重塑相关。运动训练后，年龄较大、炎症更严重、体质较差的类风湿性关节炎患者的疾病活动性改善最大。这些运动训练引起的免疫调节变化可能是通过重新编程肌肉生物能量和氨基酸/蛋白质稳态途径而发生的。 ClinicalTrials.gov，NCT02528344。注册于 2015 年 8 月 19 日。在线版本包含可在 10.1186/s13075-021-02570-3 获取的补充材料。
Exercise training, including high-intensity interval training (HIIT), improves rheumatoid arthritis (RA) inflammatory disease activity via unclear mechanisms. Because exercise requires skeletal muscle, skeletal muscle molecular pathways may contribute. The purpose of this study was to identify connections between skeletal muscle molecular pathways, RA disease activity, and RA disease activity improvements following HIIT. RA disease activity assessments and vastus lateralis skeletal muscle biopsies were performed in two separate cohorts of persons with established, seropositive, and/or erosive RA. Body composition and objective physical activity assessments were also performed in both the cross-sectional cohort and the longitudinal group before and after 10 weeks of HIIT. Baseline clinical assessments and muscle RNA gene expression were correlated with RA disease activity score in 28 joints (DAS-28) and DAS-28 improvements following HIIT. Skeletal muscle gene expression changes with HIIT were evaluated using analysis of covariance and biological pathway analysis. RA inflammatory disease activity was associated with greater amounts of intramuscular adiposity and less vigorous aerobic exercise (both p < 0.05). HIIT-induced disease activity improvements were greatest in those with an older age, elevated erythrocyte sedimentation rate, low cardiorespiratory fitness, and a skeletal muscle molecular profile indicative of altered metabolic pathways (p < 0.05 for all). Specifically, disease activity improvements were linked to baseline expression of RA skeletal muscle genes with cellular functions to (1) increase amino acid catabolism and interconversion (GLDC, BCKDHB, AASS, PYCR, RPL15), (2) increase glycolytic lactate production (AGL, PDK2, LDHB, HIF1A), and (3) reduce oxidative metabolism via altered beta-oxidation (PXMP2, ACSS2), TCA cycle flux (OGDH, SUCLA2, MDH1B), and electron transport chain complex I function (NDUFV3). The muscle mitochondrial glycine cleavage system (GCS) was identified as critically involved in RA disease activity improvements given upregulation of multiple GCS genes at baseline, while GLDC was significantly downregulated following HIIT. In the absence of physical activity, RA inflammatory disease activity is associated with transcriptional remodeling of skeletal muscle metabolism. Following exercise training, the greatest improvements in disease activity occur in older, more inflamed, and less fit persons with RA. These exercise training-induced immunomodulatory changes may occur via reprogramming muscle bioenergetic and amino acid/protein homeostatic pathways. ClinicalTrials.gov, NCT02528344. Registered on 19 August 2015. The online version contains supplementary material available at 10.1186/s13075-021-02570-3.
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影响因子：
4.7
作者：
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影响因子：
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影响因子：
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