Differential Metabolites and Metabolic Pathways Involved in Aerobic Exercise Improvement of Chronic Fatigue Symptoms in Adolescents Based on Gas Chromatography–Mass Spectrometry

Abstract

Studies have found that the prevalence of chronic fatigue syndrome (CFS) in adolescents has continued to increase over the years, affecting learning and physical health. High school is a critical stage for adolescents to grow and mature. There are inadequate detection and rehabilitation methods for CFS due to an insufficient understanding of the physiological mechanisms of CFS. The purpose of this study was to evaluate the effect and metabolic mechanisms of an aerobic running intervention program for high school students with CFS. Forty-six male high school students with CFS were randomly assigned to the exercise intervention group (EI) and control group (CFS). Twenty-four age- and sex-matched healthy male students were recruited as healthy controls (HCs). The EI group received the aerobic intervention for 12 weeks, three times a week, in 45-min sessions; the CFS group maintained their daily routines as normal. The outcome measures included fatigue symptoms and oxidation levels. Keratin was extracted from the nails of all participants, and the oxidation level was assessed by measuring the content of 3-Nitrotyrosine (3-NT) in the keratin by ultraviolet spectrophotometry. All participants’ morning urine was collected to analyze urinary differential metabolites by the GC-MS technique before and after the intervention, and MetaboAnalyst 5.0 was used for pathway analysis. Compared with before the intervention, the fatigue score and 3-NT level in the EI group were significantly decreased after the intervention. The CFS group was screened for 20 differential metabolites involving the disruption of six metabolic pathways, including arginine biosynthesis, glycerolipid metabolism, pentose phosphate pathway, purine metabolism, β-alanine metabolism, and arginine and proline metabolism. After the intervention, 21 differential metabolites were screened, involved in alterations in three metabolic pathways: beta-alanine metabolism, pentose phosphate metabolism, and arginine and proline metabolism. Aerobic exercise was found to lessen fatigue symptoms and oxidative levels in students with CFS, which may be related to the regulation of putrescine (arginine and proline metabolism), 6-Phospho-D-Gluconate (starch and sucrose metabolism pathway), and Pentose (phosphate metabolism pathway).

Mass Sportrometry: An annual look back at applications of mass spectrometry in sport and exercise science

“…25,26,28,40,52,53 In 2022, 18 studies used a traditional non-targeted metabolomics assay. 18,24,30,[83][84][85][86][87][88][89][90][91][92][93][94][95][96][97] Perhaps the most thought-provoking exercise metabolomics publication from 2022 came from the Long Lab at Stanford University and was published in Nature. This study identified an exercise-induced metabolite, namely N-lactoylphenylalanine (Lac-Phe), to be associated with reduced dietary intake.…”

“…In 2022, 18 studies used a traditional non‐targeted metabolomics assay 18,24,30,83–97 . Perhaps the most thought‐provoking exercise metabolomics publication from 2022 came from the Long Lab at Stanford University and was published in Nature .…”

“…For example, Tso and colleagues 83 They identified that improved cardiovascular parameters were associated with increases in arginine and a decrease in hypoxanthine and saturated fatty acids, with increases in lysine and pipecolate indicating adverse cardiovascular health. Similarly, Zhao et al 89 investigated metabolic health but in a non-sporting population, observing metabolomic changes following an exercise intervention in individuals diagnosed with chronic fatigue syndrome. The exercise intervention was designed to align with the aforementioned ACSM guidelines.…”

“…Similarly, Zhao et al. 89 investigated metabolic health but in a non‐sporting population, observing metabolomic changes following an exercise intervention in individuals diagnosed with chronic fatigue syndrome. The exercise intervention was designed to align with the aforementioned ACSM guidelines.…”

Efficacy of traditional Chinese exercises in patients with post-COVID-19 chronic fatigue syndrome: A protocol for systematic review and meta-analysis

“…[4][5][6] The prevalence of CFS is estimated to be between 1% and 2% globally, causing a serious burden on the work and life of patients. [7,8] It is reported that at least 1 million people in the United States have CFS and that it is three to four times more common in women than in men, with the highest prevalence in people aged 40 to 50 years, but children and adolescents are also at risk. [9] And it has a huge impact on the American economy, costing approximately $9 to 37 billion in lost productivity and $9 to 14 billion in direct medical costs annually.…”