Muscle metabolomics analysis reveals potential biomarkers of exercise‑dependent improvement of the diaphragm function in chronic obstructive pulmonary disease

Li,Jian; Lu,Yufan; Li,Ning; Li,Peijun; Su,Jianqing; Wang,Zhengrong; Wang,Ting; Yang,Zhaoyu; Yang,Yahui; Chen,Haixia; Xiao,Lu; Duan,Hongxia; Wu,Weibing; Liu,Xiaodan

doi:10.3892/ijmm.2020.4537

Muscle metabolomics analysis reveals potential biomarkers of exercise‑dependent improvement of the diaphragm function in chronic obstructive pulmonary disease

Authors:
- Jian Li
- Yufan Lu
- Ning Li
- Peijun Li
- Jianqing Su
- Zhengrong Wang
- Ting Wang
- Zhaoyu Yang
- Yahui Yang
- Haixia Chen
- Lu Xiao
- Hongxia Duan
- Weibing Wu
- Xiaodan Liu
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Affiliations: Department of Sports Medicine, Shanghai University of Sport, Shanghai 200438, P.R. China, School of Physical Education and Sport Training, Shanghai University of Sport, Shanghai 200438, P.R. China, School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
Published online on: March 12, 2020 https://doi.org/10.3892/ijmm.2020.4537
Pages: 1644-1660
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Decreased diaphragm function is a crucial factor leading to reduced ventilatory efficiency and worsening of quality of life in chronic obstructive pulmonary disease (COPD). Exercise training has been demonstrated to effectively improve the function of the diaphragm. However, the mechanism of this process has not been identified. The emergence of metabolomics has allowed the exploration of new ideas. The present study aimed to analyze the potential biomarkers of exercise‑dependent enhancement of diaphragm function in COPD using metabolomics. Sprague Dawley rats were divided into three groups: COPD + exercise group (CEG); COPD model group (CMG); and control group (CG). The first two groups were exposed to cigarette smoke for 16 weeks to establish a COPD model. Then, the rats in the CEG underwent aerobic exercise training for 9 weeks. Following confirmation that exercise effectively improved the diaphragm function, a gas chromatography tandem time‑of‑flight mass spectrometry analysis system was used to detect the differential metabolites and associated pathways in the diaphragm muscles of the different groups. Following exercise intervention, the pulmonary function and diaphragm contractility of the CEG rats were significantly improved compared with those of the CMG rats. A total of 36 different metabolites were identified in the comparison between the CMG and the CG. Pathway enrichment analysis indicated that these different metabolites were involved in 17 pathways. A total of 29 different metabolites were identified in the comparison between the CMG and the CEG, which are involved in 14 pathways. Candidate biomarkers were selected, and the pathways analysis of these metabolites demonstrated that 2 types of metabolic pathways, the nicotinic acid and nicotinamide metabolism and arginine and proline metabolism pathways, were associated with exercise‑induced pulmonary rehabilitation.

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