Author(s): PETRICK, H., HERMANS, W.J.H.1, KUIN, L.M.E.1, VERDIJK, L.B.1, VAN LOON, L.J.C.1, HOLLOWAY, G.P.2, Institution: WAGENINGEN UNIVERSITY AND RESEARCH, Country: NETHERLANDS, Abstract-ID: 1064

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.