Abstract Background and aims: Mammalian cells possess molecular clocks which adequate functioning is decisive for metabolic health. Exercise is known to modulate these clocks, potentially having distinct effects on metabolism depending on the time of day. Specific aims of this project are a) to describe possible differences dependent on sex in the diurnal variation of the effect of exercise on glycemic metabolism and fat oxidation, and b) to characterize the molecular mechanisms implicated.
Methods and results: Using a randomized crossover design, healthy men (N = 18) and women (N = 17) performed a 60 minutes bout of moderate-intensity aerobic exercise in the morning and evening. Glucose regulation was continuously monitored starting 24 hours prior to the exercise day and continued until 48 hours post-exercise for each experimental condition. Energy expenditure and substrate oxidation were measured by indirect calorimetry during exercise and at rest before and after exercise for 30 minutes. Skeletal muscle biopsies were collected immediately before and after exercise to assess mitochondrial function, transcriptome and mitochondrial proteome.
Results indicated similar systemic glucose, energy expenditure and substrate oxidation during and after exercise in both sexes. Notably, transcriptional analysis, mitochondrial function, and mitochondrial proteomics revealed marked sexual dimorphism and time of day variations.
Conclusion: The present study shows that there are distinct molecular responses to exercise in skeletal muscle based on the time of day and sex, although one single session of moderate-intensity aerobic exercise is not enough to reflect it in systemic adaptations. Our results illustrate that the time of day of exercise impact more importantly on women, resulting exercise a stronger stimulus in the evening and producing a metabolic response with higher reliance on carbohydrates at this time of day. It would be premature to make clinical recommendations in this regard, but here we provide a molecular framework for future research.
Clinical Trials: ClinicalTrials.gov: NCT05369715
This study received funding from various sources including the Spanish Ministry of Culture and Sport, Consejo Superior de Deportes, Plan de Recuperación, Transformación y Resiliencia, the European Union through Next Generation EU, Ayudas europeas a proyectos de investigación aplicada a la Actividad Física Beneficiosa para la Salud y la Medicina Deportiva (EXP_77437), the Spanish Ministry of Science and Innovation (PID2022-141506OB-I00), the European Regional Development Funds (ERDF), the University of Granada Plan Propio de Investigación-Excellence actions: Unit of Excellence on Exercise Nutrition and Health (UCEENS), as well as individual grants including those supporting R.S.L and A.M.P (FPU19/03745 and FPU20/05530, respectively), and J.M.A.A. (Juan de la Cierva-Formación Grant FJC2020-044453-I). S. C. received a “Ramón y Cajal fellowship 23013-2017” funded by MCIN/AEI, and research in her lab is partially supported by the Grant PID2020-114054RA-I00. Research in L.C.L. lab is supported by a grant from MCIN/AEI, Spain, and the ERDF (PID2021-126788OB-I00). This work is part of a doctorate thesis conducted in the Official Doctoral Program in Biomedicine of the University of Granada, Spain.
