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Metabolites
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Metabolic Responses to Exercise and Nutrition: From Molecular Mechanisms to...
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Metabolic Responses to Exercise and Nutrition: From Molecular Mechanisms to Functional Performance

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: 20 August 2026 | Viewed by 2230

Special Issue Editors

Dr. Do-Houn Kim

E-Mail Website
Guest Editor
Department of Human Physiology, Gonzaga University, Spokane, WA 99258, USA
Interests: exercise physiology; metabolism; sport nutrition; vitamin D metabolism; skeletal muscle metabolism
Dr. Chang Liu

E-Mail Website
Guest Editor
School of Sport Science, Beijing Sport University, Beijing 100084, China
Interests: molecular mechanisms; exercise metabolism; nutritional metabolites; performance enhancement

Special Issue Information

Dear Colleagues,

Physical activity and nutrition are fundamental pillars of human health, and their synergistic effects are mediated through complex metabolic networks that influence physiological function across multiple organ systems. The emergence of high-throughput metabolomics has transformed our capacity to comprehensively characterize the metabolic consequences of exercise and nutritional interventions, enabling researchers to move beyond traditional reductionist approaches toward a systems-level understanding of how lifestyle factors shape human metabolism and functional capacity.

This Special Issue, titled “Metabolic Responses to Exercise and Nutrition: From Molecular Mechanisms to Functional Performance”, seeks to integrate cutting-edge metabolomic research with exercise physiology and nutritional science to advance our understanding of how metabolic adaptations translate into improved movement capacity, physical performance, and health outcomes. We aim to bridge the gap between molecular metabolic processes and their functional manifestations in human movement and performance.

We invite original research articles and comprehensive reviews that employ metabolomic approaches to investigate the interplay among exercise, nutrition, and metabolism. Topics of particular interest include the identification of metabolic signatures associated with different exercise modalities, intensities, and training adaptations; the characterization of nutritional metabolites that modulate exercise responses and recovery; the discovery of biomarkers that predict or correlate with functional performance outcomes such as strength, endurance, and movement quality; the elucidation of metabolic pathways underlying the combined effects of dietary interventions and physical activity on health and disease; the application of metabolomics to personalized nutrition and exercise prescription; and the investigation of metabolic mechanisms linking exercise–nutrition interactions to improvements in chronic disease management. Studies examining inter-organ metabolic crosstalk during exercise and feeding, the temporal dynamics of metabolic responses to acute and chronic interventions, and the integration of metabolomics with other omics technologies are particularly encouraged.

This Special Issue will provide a platform for innovative research that accelerates the translation of metabolomic insights into evidence-based strategies for optimizing human health, performance, and functional capacity through integrated exercise and nutritional interventions.

Dr. Do-Houn Kim
Dr. Chang Liu
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metabolomics
  • exercise metabolism
  • nutritional metabolites
  • biomarkers
  • functional performance
  • physical activity
  • metabolic adaptation
  • movement capacity
  • exercise–nutrition interactions
  • personalized nutrition

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Published Papers (2 papers)

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Research

22 pages, 2610 KB  
Article
Remodeling of the Mouse Liver and Skeletal Muscle Metabolome in Response to Continuous Acute Exercise and Disruption of AMPK-Glycogen Interactions
by Mehdi R. Belhaj, David I. Broadhurst, Thomas Dignan, Jamie Whitfield, Lisa Murray-Segal, Naomi X. Y. Ling, Jonathan S. Oakhill, Bruce E. Kemp, John A. Hawley, Stacey N. Reinke and Nolan J. Hoffman
Metabolites 2026, 16(3), 205; https://doi.org/10.3390/metabo16030205 - 20 Mar 2026
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Abstract
Background/Objectives: Acute exercise remodels many interconnected biochemical pathways in metabolically active tissues. This remodeling involves the activation of the energy-sensing AMP-activated protein kinase (AMPK) to maintain cellular energy homeostasis. Critical energy reserves of glycogen, primarily stored in liver and skeletal muscle and [...] Read more.
Background/Objectives: Acute exercise remodels many interconnected biochemical pathways in metabolically active tissues. This remodeling involves the activation of the energy-sensing AMP-activated protein kinase (AMPK) to maintain cellular energy homeostasis. Critical energy reserves of glycogen, primarily stored in liver and skeletal muscle and known to interact with AMPK, are utilized to help meet increased energy demands with exercise. However, the breadth of metabolic pathways regulated by acute exercise and AMPK’s interactive roles with glycogen remain incompletely understood. This study therefore aimed to map mouse liver and skeletal muscle metabolite responses to continuous acute exercise and disruption of AMPK-glycogen interactions. Methods: Liquid chromatography–mass spectrometry-based untargeted metabolomics was used to measure the relative abundance of liver and gastrocnemius muscle metabolites at rest and following an acute bout of continuous treadmill running in wild type (WT) and AMPK transgenic mice with double knock-in (DKI) mutations in the β subunit carbohydrate binding module that mediates glycogen binding. Results: Over 200 total metabolites were identified/annotated across liver and skeletal muscle, including 45 metabolites responsive to exercise (p < 0.05; FDR < 0.1). Exercise-regulated metabolites included known metabolic pathways and metabolites never associated or with only emerging evidence related to exercise (e.g., ergothioneine) and/or AMPK-glycogen interactions (N6,N6,N6-trimethyl-L-lysine, a precursor of L-carnitine). Conclusions: Liver and skeletal muscle metabolomic profiles displayed shifts between WT and DKI mice at rest, with shifts also detected following a continuous acute exercise bout. An interaction effect was also observed in skeletal muscle, suggesting differential muscle metabolite responses to acute exercise in DKI mice that may contribute to their functional impairments in metabolic control and exercise capacity versus WT. Collectively, these findings expand the molecular landscape of acute exercise and reveal liver and muscle metabolites underlying exercise-induced metabolic responses. Full article
(This article belongs to the Special Issue Metabolic Responses to Exercise and Nutrition: From Molecular Mechanisms to Functional Performance)
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18 pages, 2211 KB  
Article
Metabolomic Signatures of Recovery: A Secondary Analysis of Public Longitudinal LC–MS Datasets Shows Polyphenol-Rich Interventions Attenuate Purine Degradation and Oxidative Stress Following Exhaustive Exercise
by Xuyang Wang, Chang Liu, Yirui Chen, Mengyang Wang, Kai Zhao and Wei Jiang
Metabolites 2026, 16(1), 79; https://doi.org/10.3390/metabo16010079 - 16 Jan 2026
Cited by 4 | Viewed by 804
Abstract
Background: Post-exercise recovery involves coordinated metabolic restoration and redox rebalancing. Although dietary polyphenols have been proposed to facilitate recovery, the metabolic mechanisms underlying their effects—particularly during the recovery phase—remain insufficiently characterized. This study aimed to investigate how polyphenol supplementation modulates post-exercise metabolic recovery [...] Read more.
Background: Post-exercise recovery involves coordinated metabolic restoration and redox rebalancing. Although dietary polyphenols have been proposed to facilitate recovery, the metabolic mechanisms underlying their effects—particularly during the recovery phase—remain insufficiently characterized. This study aimed to investigate how polyphenol supplementation modulates post-exercise metabolic recovery using an integrative metabolomics approach. Methods: We conducted a secondary analysis of publicly available longitudinal human LC–MS metabolomics datasets from exercise intervention studies with polyphenol supplementation. Datasets were obtained from the NIH Metabolomics Workbench and MetaboLights repositories; study-level metadata were used as provided by the original investigators. Global metabolic trajectories were assessed using principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Targeted analyses focused on purine degradation intermediates and redox-related metabolites. Correlation-based network and pathway enrichment analyses were applied to characterize recovery-phase metabolic reorganization. Results: Exercise induced a pronounced global metabolic perturbation in both placebo and polyphenol groups. During recovery, polyphenol supplementation was associated with a partial reversion of the metabolome toward the pre-exercise state, whereas placebo samples remained metabolically displaced. Discriminant metabolite analyses identified purine degradation intermediates and oxidative stress-related lipid species as key contributors to group separation during recovery. Polyphenol supplementation attenuated recovery-phase accumulation of hypoxanthine, xanthine, and uric acid and was associated with a sustained suppression of the uric acid-to-hypoxanthine ratio. Network analyses revealed weakened correlations between purine metabolites and oxidative stress markers, along with reduced network centrality of stress-responsive metabolic hubs. Conclusions: These findings indicate that polyphenol supplementation is associated with accelerated metabolic normalization during post-exercise recovery, potentially through modulation of purine-associated oxidative pathways and system-level metabolic network reorganization. Full article
(This article belongs to the Special Issue Metabolic Responses to Exercise and Nutrition: From Molecular Mechanisms to Functional Performance)
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