Sexual dimorphism on the acute effect of exercise in the morning vs. evening: A randomized crossover study.

BACKGROUND: Mammalian cells possess molecular clocks, the adequate functioning of which is decisive for metabolic health. Exercise is known to modulate these clocks, potentially having distinct effects on metabolism depending on the time of day. This study aimed to investigate the impact of morning vs. evening moderate-intensity aerobic exercise on glucose regulation and energy metabolism in healthy men and women. It also aimed to elucidate molecular mechanisms within skeletal muscle. METHODS: Using a randomized crossover design, healthy men (n = 18) and women (n = 17) performed a 60-min bout of moderate-intensity aerobic exercise in the morning and evening. Glucose regulation was continuously monitored starting 24 h prior to the exercise day and continuing until 48 h 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 min. Skeletal muscle biopsies were collected immediately before and after exercise to assess mitochondrial function, transcriptome, and mitochondrial proteome. RESULTS: 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 sexual dimorphism and time of day variations observed in the skeletal muscle in response to exercise may translate into observable systemic effects with higher exercise-intensity or chronic exercise interventions. This study provides a foundational molecular framework for precise exercise prescription in the clinical setting.