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Exercise intensity determines circulating levels of Lac-Phe and other exerkines: a randomized crossover trial

Dirk Weber, Paola G. Ferrario, Achim Bub

2025Metabolomics21 citationsDOIOpen Access PDF

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: ) 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).

Topics & Concepts

Aerobic exerciseCrossover studyExercise intensityIntensity (physics)Internal medicineMetabolomicsAmino acidExercise physiologyCycle ergometerMedicineEndocrinologyChemistryPhysical therapyBiologyBiochemistryBioinformaticsBlood pressureHeart ratePlaceboPathologyAlternative medicineQuantum mechanicsPhysicsMetabolomics and Mass Spectrometry StudiesMuscle metabolism and nutritionExercise and Physiological Responses
Exercise intensity determines circulating levels of Lac-Phe and other exerkines: a randomized crossover trial | Litcius