{"title":"Exercise intensity determines circulating levels of Lac-Phe and other exerkines: a randomized crossover trial.","authors":"Dirk Weber, Paola G Ferrario, Achim Bub","doi":"10.1007/s11306-025-02260-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Exercise metabolomics research has revealed significant exercise-induced metabolic changes and identified several exerkines as mediators of physiological adaptations to exercise. However, the effect of exercise intensity on metabolic changes and circulating exerkine levels remains to be examined.</p><p><strong>Objectives: </strong>This study compared the metabolic responses to moderate-intensity and vigorous-intensity aerobic exercise.</p><p><strong>Methods: </strong>A two-period crossover trial was conducted under controlled conditions at the Max Rubner-Institute in Karlsruhe, Germany. Seventeen young, healthy, and physically active men performed 30 min moderate-intensity (50% VO<sub>2peak</sub>) and vigorous-intensity (75% VO<sub>2peak</sub>) aerobic exercise using two bicycle ergometer protocols in a randomized sequence. Blood samples obtained immediately before exercise and at four time points after exercise were analyzed in an untargeted metabolomics approach, and separate linear mixed models were applied to over 1000 metabolites.</p><p><strong>Results: </strong>Vigorous-intensity exercise induced a greater metabolic response than moderate-intensity exercise. Several intensity-dependent metabolites were identified, primarily involved in amino acid metabolism and energy conversion pathways, including N-lactoyl-amino acids, TCA cycle intermediates, N-acetylated amino acids, and acylcholines. The exerkines N-lactoyl-phenylalanine, lactate, and succinate were among the most intensity-dependent metabolites. N-acetylated amino acids and acylcholines were systematically altered by exercise intensity, indicating potential physiological functions.</p><p><strong>Conclusion: </strong>Exercise intensity significantly affects exercise-induced metabolic alterations and changes in exerkine levels. Our results expand the knowledge about exerkine dynamics and emphasize the role of exercise intensity in promoting physiological adaptations to exercise. The trial was registered on October 5, 2017, at the German Clinical Trials Register under the Registration Number DRKS00009743 (Universal Trial Number of WHO: U1111-1200-2530).</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":"21 3","pages":"63"},"PeriodicalIF":3.5000,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058925/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Metabolomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11306-025-02260-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Exercise metabolomics research has revealed significant exercise-induced metabolic changes and identified several exerkines as mediators of physiological adaptations to exercise. However, the effect of exercise intensity on metabolic changes and circulating exerkine levels remains to be examined.
Objectives: This study compared the metabolic responses to moderate-intensity and vigorous-intensity aerobic exercise.
Methods: A two-period crossover trial was conducted under controlled conditions at the Max Rubner-Institute in Karlsruhe, Germany. Seventeen young, healthy, and physically active men performed 30 min moderate-intensity (50% VO2peak) and vigorous-intensity (75% VO2peak) aerobic exercise using two bicycle ergometer protocols in a randomized sequence. Blood samples obtained immediately before exercise and at four time points after exercise were analyzed in an untargeted metabolomics approach, and separate linear mixed models were applied to over 1000 metabolites.
Results: Vigorous-intensity exercise induced a greater metabolic response than moderate-intensity exercise. Several intensity-dependent metabolites were identified, primarily involved in amino acid metabolism and energy conversion pathways, including N-lactoyl-amino acids, TCA cycle intermediates, N-acetylated amino acids, and acylcholines. The exerkines N-lactoyl-phenylalanine, lactate, and succinate were among the most intensity-dependent metabolites. N-acetylated amino acids and acylcholines were systematically altered by exercise intensity, indicating potential physiological functions.
Conclusion: Exercise intensity significantly affects exercise-induced metabolic alterations and changes in exerkine levels. Our results expand the knowledge about exerkine dynamics and emphasize the role of exercise intensity in promoting physiological adaptations to exercise. The trial was registered on October 5, 2017, at the German Clinical Trials Register under the Registration Number DRKS00009743 (Universal Trial Number of WHO: U1111-1200-2530).
期刊介绍：
Metabolomics publishes current research regarding the development of technology platforms for metabolomics. This includes, but is not limited to:
metabolomic applications within man, including pre-clinical and clinical
pharmacometabolomics for precision medicine
metabolic profiling and fingerprinting
metabolite target analysis
metabolomic applications within animals, plants and microbes
transcriptomics and proteomics in systems biology
Metabolomics is an indispensable platform for researchers using new post-genomics approaches, to discover networks and interactions between metabolites, pharmaceuticals, SNPs, proteins and more. Its articles go beyond the genome and metabolome, by including original clinical study material together with big data from new emerging technologies.
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