ECSS Paris 2023: OP-PN38
INTRODUCTION: Substrate utilization is highly regulated during exercise. Mitochondria are dominant organelles in these processes, as mitochondria are essential for energy production and coordinating fat and carbohydrate oxidation. As fat oxidation during exercise is higher in females compared to males, it is possible there are sex-based differences in mitochondrial substrate interactions. Here, we examined mitochondrial ADP, pyruvate, and carnitine palmitoyltransferase-I (CPT-I) substrate sensitivity in skeletal muscle of males and females following acute treadmill running, as possible mechanisms contributing to sex-based differences in substrate utilization. METHODS: 10 recreationally active males (age 24±4 y, BMI 23.7±2.9 kg/m2, VO2peak 54±7 mL/kg/min) and 10 females (age 22±2 y, BMI 22.9±1.8 kg/m2, VO2peak 44±3 mL/kg/min) participated in this study. On the experimental test-day, a fasted, rested, muscle biopsy was obtained from the m. vastus lateralis. Participants then completed a 5 min warm-up on a treadmill (7 km/h males, 6 km/h females), followed by a 40 min treadmill run at ~85% of maximal heart rate. Immediately following the running bout, a second fasted muscle biopsy was obtained. Mitochondrial respiration was measured in permeabilized muscle fibres using an Oroboros O2k Oxygraph. Data were analyzed using unpaired two-tailed t-tests (male vs female) or paired two-tailed t-tests (pre- vs post-exercise). Statistical significance was set at P<0.05. All data are expressed as mean±SD. RESULTS: Male participants had a ~25% higher VO2peak relative to total body mass compared to females (P=0.0004), while VO2peak relative to lean body mass did not significantly differ between sexes (69±7 vs 63±6 mL/kg lean mass/min, respectively, P=0.07). There were no differences in maximal mitochondrial capacity within skeletal muscle of males vs females at rest (P>0.15), but submaximal mitochondrial respiration (25, 100 µM ADP) tended to be lower in females (P=0.06). Following exercise, mitochondrial ADP sensitivity had decreased ~25% in both males (increased half-time from 962±174 to 1207±127 µM ADP, P=0.009) and females (from 1021±184 to 1218±204 µM ADP, P=0.001), in the absence of changes in pyruvate sensitivity. In males, exercise did not alter CPT-I-supported respiration (palmitoyl-CoA and maximal L-carnitine, from 50±9 to 53±5 pmol/s/mg, P>0.37), while sensitivity to L-carnitine was ~20% lower post-exercise (from 36±9 to 44±12 µM L-carnitine, P=0.04). In contrast, in females, treadmill running increased CPT-I-supported respiration by ~25% (from 45±4 to 56±12 pmol/s/mg, P=0.007) without altering L-carnitine sensitivity (from 37±9 to 42±15 µM L-carnitine, P=0.20). CONCLUSION: The effects of exercise on mitochondrial ADP and pyruvate sensitivity are consistent in both males and females. However, mitochondrial CPT-I-supported respiration is differentially regulated following acute treadmill running in males and females, which could be relevant to differences in substrate selection during exercise.
Read CV Heather PetrickECSS Paris 2023: OP-PN38
INTRODUCTION: The salutary effects of regular physical activity on cardiovascular and metabolic health are well established. While precise understanding of the cellular and molecular processes underlying those benefits remain incompletely understood, accumulating evidence suggests that acute bouts of exercise trigger a transient immune and inflammatory response that may act as a key mediator of long-term physiological adaptations. Modulation of exercise intensity is known to modulate the magnitude of those transient responses. Importantly, current World Health Organization (WHO) guidelines recommend either 150 min of moderate- or 75 min of vigorous-intensity physical activity per week, yet the acute molecular signatures elicited by these clinically relevant intensities have not been directly compared. Herein, we aimed to assess and directly compare the acute proteomic response to 30 minutes of moderate vs. vigorous treadmill exercise in a cross-over design. METHODS: Young healthy sedentary individuals underwent maximal effort-limited cardiopulmonary exercise test to determine peak oxygen uptake (VO2PEAK) and the first ventilatory threshold (VT1). Subsequently, each participant performed both a moderate (workloads corresponding with VT1−15%) and vigorous (workloads corresponding with VT1+15%) bout of treadmill exercise, each lasting 30 min. Both sessions were conducted after an overnight fast and were separated by ≥ 4 weeks. Heart rate (HR) was continuously recorded using a chest strap (Polar H10). Blood samples were collected pre-exercise and immediately post-exercise for targeted proteomic profiling of the immune and inflammatory response (Olink REVEAL panel). Proteins were defined as “exercise responsive” based on a fold change > ∣1,2∣ and an FDR < 0.05. RESULTS: Six women and six men (age = 23 ± 5 years, VO2PEAK = 41 ± 8 ml/kg/min) participated in this study. As expected, vigorous exercise resulted in a greater average HR than moderate exercise (82 ± 9% vs. 66 ± 8% of HR peak, p < 0.05). Among the 1034 proteins assayed, none showed statistically significant changes in abundance in response to 30 min of moderate exercise. In contrast, vigorous exercise triggered a broad systemic response. We identified a significant change in 394 proteins (38% of the assayed panel), almost exclusively characterized by up-regulation. This vigorous-intensity signature was heavily enriched with mediators of cytokine and chemokine signalling, reflecting a robust activation of the systemic immune system. CONCLUSION: These findings extend previous work by demonstrating that vigorous, but not moderate, acute exercise elicits a broad systemic immune and inflammatory response in young healthy adults. Further work is required to determine the extent to which this distinct immune and inflammatory response mediates long-term physiological adaptation in both the primary and secondary prevention setting.
Read CV Tarik Moufid TrambatyECSS Paris 2023: OP-PN38