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

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.

Effects of exercise on NAFLD using non-targeted metabolomics in adipose tissue, plasma, urine, and stool

“…This causes irisin release, thereby promoting the browning of beige fat cells in white adipose tissue, enhanced thermogenesis, increased energy expenditure, and maintenance of glucose homeostasis 42 , 43 . The increase of threonine levels in vivo in the intervention group could be partially responsible for these beneficial effects; however, further studies are warranted 44 . Similarly, the increase of tyrosine levels as observed from the metabolomic and pathway analysis (Fig.…”

Effect of Oxidative Stress on Diaphragm Dysfunction and Exercise Intervention in Chronic Obstructive Pulmonary Disease

“… Vieira Ramos et al (2018) conducted treadmill aerobic training on mice with COPD and found that it improved the antioxidant capacity of the diaphragm. Li et al (2020) found that after aerobic exercise in water, the nicotinic acid metabolism level in the diaphragm of COPD rats was upregulated, thus protecting the diaphragm and ventilatory muscle from oxidative damage and improving diaphragm muscle strength and ventilatory function. However, this experiment did not directly detect oxidative stress indicators.…”

Regulation of Whole-Transcriptome Sequencing Expression in COPD after Personalized Precise Exercise Training

“…Aerobic exercise is a cornerstone of pulmonary rehabilitation(PR) to improve health-related quality of life and exercise capacity, as well as reduce dyspnea, hospitalization, exacerbation, and mortality 9,10,11 . Some studies suggest that exercises can reduce chronic in ammation, improve the diaphragm and cognitive function, and reverse airway remodeling 12,13,14,15 . However, despite exercise's profound bene ts for treating COPD, knowledge of how exercise improves health and the molecular mechanism of immunometabolism response to exercise remains limited 43,45 .…”