Acute Exercise-Associated Metabolomic Remodeling and Associations with Oxidative State in Human Skeletal Muscle
6 affiliations
- 1School of Sport Science, Beijing Sport University, Beijing 100084, China
- 2China Basketball College, Beijing Sport University, Beijing 100084, China
- 3School of International Education and Exchange, Beijing Sport University, Beijing 100084, China
- 4School of Art, Beijing Sport University, Beijing 100084, China
- 5China Volleyball Academy, Beijing Sport University, Beijing 100084, China
- 6School of Education, Beijing Sport University, Beijing 100084, China
Abstract
Background: Acute exercise rapidly reorganizes skeletal-muscle metabolism. The metabolite pools that remain responsive with aging, and their relationship to baseline oxidative state, remain incompletely defined. Methods: We analyzed 135 metabolites measured in 93 skeletal-muscle biopsies from 47 participants and matched baseline transcriptomic measurements. We tested paired post–pre changes, biochemical-class enrichment, baseline associations with a four-pathway oxidative transcript-state score, and participant-held-out prediction of acetylcarnitine response. False-discovery-rate control was applied within each analysis family. Bootstrap confidence intervals and a baseline-adjusted sensitivity analysis quantified predictive performance. Results: In exercise-trained older adults, 17 metabolites changed after acute exercise after FDR correction. Acetylcarnitine increased, whereas free carnitine, malate, ATP, and choline decreased. No exercise-trained-versus-normally active response contrast survived correction. The CoA–glutathione-annotated feature and NAD+ remained associated with the oxidative transcript-state score after adjustment for group and sex (partial ρ=0.512 and 0.514; both q=0.042). A four-metabolite TabPFN model predicted acetylcarnitine change with an out-of-fold R2 of 0.412 (95% CI, 0.079–0.641), similar to the reference model (R2=0.399, 95% CI, 0.054–0.625). Baseline acetylcarnitine alone achieved an AUC of 0.817 (95% CI, 0.680–0.941) for a twofold-response endpoint. Additional metabolites provided only modest incremental information after baseline adjustment. Conclusions: Acute exercise induced heterogeneous, distributed remodeling of skeletal-muscle metabolite pools. Baseline redox-related molecular state showed cross-omic coherence and contained information about subsequent acetylcarnitine response. Transcriptomic augmentation and more complex predictive architectures provided limited incremental benefit.
Related
- Interferon-Associated Inflammatory Remodeling and Oxidative Metabolic Repression Define the Skeletal Muscle Transcriptomic Landscape of δ-Sarcoglycan Deficiency
- Exercise-Associated Gut Microbiota Remodeling and Cardiovascular Protection: Potential Mechanisms Involving Inflammatory Regulation
- Organ-Differentiated Metabolomic Profiling Reveals Putative Associations Between Predicted Bioactivity and Database-Annotated Flavor in Medicinal–Edible Talinum paniculatum (Jacq.) Gaertn
- Baseline-referenced plasma metabolomic trajectories during early post-exercise recovery: A secondary analysis of public human exercise metabolomics data
- Integrated metabolomic and transcriptomic analyses reveal tissue-specific distribution and gene-metabolite associations of quality-related metabolites in the Tibetan Plateau turnip landrace "Yushuyuangen" (Brassica rapa ssp. rapa).
BibTeX
@article{liu2026acute,
title = {{Acute Exercise-Associated Metabolomic Remodeling and Associations with Oxidative State in Human Skeletal Muscle}},
author = {Chang Liu and Qisen Han and Yao Yan and Biaoxu Tao and Meiling Liu and Xincheng Dai and Zhiqin Xu and Wei Jiang and Kai Zhao and Song Yan},
journal = {Metabolites},
year = {2026},
month = oct,
doi = {10.3390/metabo16100763},
url = {https://www.mdpi.com/2218-1989/16/10/763},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Acute Exercise-Associated Metabolomic Remodeling and Associations with Oxidative State in Human Skeletal Muscle
AU - Chang Liu
AU - Qisen Han
AU - Yao Yan
AU - Biaoxu Tao
AU - Meiling Liu
AU - Xincheng Dai
AU - Zhiqin Xu
AU - Wei Jiang
AU - Kai Zhao
AU - Song Yan
PY - 2026
DA - 2026/10/10
JO - Metabolites
DO - 10.3390/metabo16100763
UR - https://www.mdpi.com/2218-1989/16/10/763
AB - Background: Acute exercise rapidly reorganizes skeletal-muscle metabolism. The metabolite pools that remain responsive with aging, and their relationship to baseline oxidative state, remain incompletely defined. Methods: We analyzed 135 metabolites measured in 93 skeletal-muscle biopsies from 47 participants and matched baseline transcriptomic measurements. We tested paired post–pre changes, biochemical-class enrichment, baseline associations with a four-pathway oxidative transcript-state score, and participant-held-out prediction of acetylcarnitine response. False-discovery-rate control was applied within each analysis family. Bootstrap confidence intervals and a baseline-adjusted sensitivity analysis quantified predictive performance. Results: In exercise-trained older adults, 17 metabolites changed after acute exercise after FDR correction. Acetylcarnitine increased, whereas free carnitine, malate, ATP, and choline decreased. No exercise-trained-versus-normally active response contrast survived correction. The CoA–glutathione-annotated feature and NAD+ remained associated with the oxidative transcript-state score after adjustment for group and sex (partial ρ=0.512 and 0.514; both q=0.042). A four-metabolite TabPFN model predicted acetylcarnitine change with an out-of-fold R2 of 0.412 (95% CI, 0.079–0.641), similar to the reference model (R2=0.399, 95% CI, 0.054–0.625). Baseline acetylcarnitine alone achieved an AUC of 0.817 (95% CI, 0.680–0.941) for a twofold-response endpoint. Additional metabolites provided only modest incremental information after baseline adjustment. Conclusions: Acute exercise induced heterogeneous, distributed remodeling of skeletal-muscle metabolite pools. Baseline redox-related molecular state showed cross-omic coherence and contained information about subsequent acetylcarnitine response. Transcriptomic augmentation and more complex predictive architectures provided limited incremental benefit.
SN - 2218-1989
ER -