ECSS Paris 2023: OP-PN35
INTRODUCTION: Muscle glycogen is an important substrate during moderate to high intensity exercise, while repletion of muscle glycogen after exercise is often prioritized during recovery. The enzymatic regulation of glycogen breakdown and resynthesis is directly impacted by cytosolic ADP and glycolytic flux. This raises the possibility that the sensitivity of mitochondria to oxidative substrates may represent an important control point in glycogen breakdown and resynthesis. We therefore examined muscle glycogen content and the sensitivity of mitochondria to ADP, pyruvate, and ketone bodies (KB) in human skeletal muscle following exercise and during prolonged post-exercise recovery with or without carbohydrate intake. METHODS: 12 endurance-trained male cyclists (25 ± 5 y, VO2peak: 67 ± 5 mL/kg/min) performed two test-days in a randomized cross-over design. On both test-days, a standardized glycogen depletion protocol was performed on a cycle ergometer in a fasted state. The protocol lasted 125 ± 13 min and 124 ± 14 min, consisting of 2 min blocks alternating between high and low intensity cycling. During the subsequent 12 h of post-exercise recovery, participants either remained fasted or consumed 10 g/kg body mass carbohydrate (CHO). Muscle biopsies were obtained from the vastus lateralis before and after exercise, and following 6 and 12 h of post-exercise recovery. Mitochondrial respiration and substrate sensitivity were measured in permeabilized muscle fibres using an Oroboros O2k Oxygraph. Muscle glycogen content was determined in freeze-dried whole muscle homogenate. Data were analyzed using a one-way repeated-measures ANOVA with Tukey’s post-hoc tests. Statistical significance was set at P<0.05. All data are expressed as mean ± SD. RESULTS: Following exercise, mitochondrial ADP sensitivity decreased ~15% on both trials (P<0.008), correlating (r=-0.587, P=0.045 fasted day; r=-0.568, P=0.054 CHO day) with the extent of glycogen depletion during exercise. On the post-exercise fasted trial, mitochondrial ADP sensitivity returned to baseline after 6 h of recovery, but decreased once again after 12 h of post-exercise fasting (~15% decrease, P=0.037). Pyruvate sensitivity increased following exercise and declined with post-exercise fasting. However, neither pyruvate nor ADP sensitivity were altered during post-exercise recovery when consuming CHO. Furthermore, there were no relationships between changes in mitochondrial substrate sensitivity and muscle glycogen repletion during post-exercise recovery with CHO ingestion. Regardless of exercise, fasting, or CHO ingestion, KBs contributed minimally to respiration at all time-points (~2-6% of maximal complex I+II-linked respiration). CONCLUSION: Combined, the exercise-induced decrease in mitochondrial ADP sensitivity may be a mechanism promoting glycogen utilization during exercise. However, changes in mitochondrial substrate sensitivity do not appear to relate to glycogen resynthesis during post-exercise recovery when carbohydrates are ingested.
Read CV Heather PetrickECSS Paris 2023: OP-PN35
INTRODUCTION: Physical deconditioning has been shown to impact main conduit arteries and decrease post-occlusion hyperemic leg blood flow response, although findings vary depending on the duration and model of disuse (1,2). Endothelial nitric oxide (NO) release following a shear stress stimulus is a key mediator of vasodilatation, facilitated by the sequential conversion of nitrate (NO3-) to nitrite (NO2-) to NO (3). This study aimed to evaluate the effects of 14 days of step count reduction and subsequent retraining on nitrate and nitrite in different body compartments and skeletal muscle microvascular responsiveness. METHODS: We recruited 16 (n=8 women) young, healthy, normally active participants. After baseline (BDC) data collection, they underwent 14 days of step reduction (SR; 1500 steps/day) followed by a retraining (RT) period incorporating endurance and strength exercises. Measurements were performed at BDC, post-SR, and post-RT. Resting diastolic (DBP) and systolic (SBP) blood pressure were assessed at each time point. Microvascular post-occlusive reactive hyperemia in the vastus lateralis muscle was assessed by near-infrared spectroscopy. During the 30 s post-ischemia, the rate of change in tissue oxygenation index (Slope 2) was calculated. Saliva, blood, and vastus lateralis muscle samples were collected and NO3- and NO2- concentrations were determined by chemiluminescence. One-way repeated measures ANOVA and post-hoc tests were used to determine differences in the investigated variables. RESULTS: Daily step count was reduced by 82% during SR and increased with RT, but did not returnto baseline (8429±1659, all p<0.001). At BDC, DBP and SBP were 79±5 mmHg and 122±9 mmHg, respectively, and they did not change at any time points (p=0.12). Slope2 decreasd from BDC to SR (1.40±0.69%*s-1 vs. 1.00±0.29%*s-1; p<0.01) and partially recovered in RT (1.03±0.51%*s-1; p=0.04). At BDC, saliva [NO3-] and [NO2-] were 608±253 M and 102±50 M, respectively, with no changes across time (p=0.29). Plasma [NO3-] was not affected by the interventions. Plasma and muscle [NO2-] significantly increased from BDC (115±42 nM and 1.2±0.3 nmol*g-1) to SR (160±74 nM and 1.6±0.8 nmol*g-1, all p<0.03), and they partially recovered after RT. Muscle [NO3-] decreased (-37±3%) at SR. CONCLUSION: Fourteen days of SR impaired hypoxic vasodilation at the microvascular level without affecting resting blood pressure. While salivary nitrate-nitrite metabolism did not change, plasma and muscle nitrite concentrations increased during SR, and muscle nitrate content decreased, possibly reflecting a compensatory mechanism related to impaired endothelial NO production. Retraining partially restored NO metabolite distribution across body compartments. REFERENCES 1 Bleeker et al, 2005 2 de Groot et al, 2006 3 Cosby et al, 2003
Read CV Simone PorcelliECSS Paris 2023: OP-PN35
INTRODUCTION: Creatine is well-known for supporting skeletal muscle function during periods of high-intensity exercise, through the rapid provision of high-energy phosphates. Despite growing interest in the role of creatine in supporting brain health, evidence of the response of creatine concentrations in the brain, to exercise, is limited. We aimed to determine the response of total creatine concentrations (tCr) in multiple brain regions to an acute bout of vigorous exercise in humans. METHODS: Nine healthy adults aged between 23 and 30 years [6 female, age (mean ± SD) = 26.3 ± 2.8 years; body mass index = 22.7 ± 2.5 kg/m2] completed a graded cycle ergometry test lasting ~15 minutes and reaching ~85% of predicted heart rate maximum. Single-voxel proton magnetic resonance spectroscopy (1H-MRS; 20mm3 voxel) was acquired at 3T on a Siemens MAGNETOM VIDA from the visual cortex and frontal cortex before (PRE), 15- (POST15) and 30-minutes (POST30) after exercise. Multi-voxel 2D proton chemical shift imaging (1H-CSI; 80mm2 grid, 15mm slice thickness) was also acquired across the midbrain PRE and 25-minutes after exercise (POST25, taken between repeated 1H-MRS measurements). OSPREY was used to determine tCr concentrations from 1H-MRS data and TARQUIN was used to examine tCr resonance signals from 1H-CSI data. Voxel tissue fractions and relocalisation accuracy were assessed. One-way repeated measures ANOVAs and paired t-tests were used to test for exercise-induced changes in tCr. RESULTS: Following an acute bout of exercise, tCr concentrations decreased by 9.8% in the frontal cortex by POST15 (6.27 vs 6.95 mmol/L, p < 0.001), and remained significantly lower (by 5.2%) than PRE levels at POST30 (6.59 vs 6.95 mmol/L, p < 0.001), although there were signs of a gradual return to baseline concentrations. Multi-voxel 1H-CSI revealed that, overall, tCr resonance signals were significantly lower (by 8.7%) across the midbrain at POST20 compared with PRE levels (area under curve = 808.01 vs 737.80 a.u., p = 0.044), although region specific responses were shown. No significant responses to exercise were shown in the visual cortex at any timepoint (tCr concentrations = 7.84 vs 7.67 vs 7.81 mmol/L at PRE, POST15 and POST30; all p > 0.05). CONCLUSION: tCr concentrations in certain regions of the young adult brain are dynamic and respond acutely to exercise, demonstrating the reliance of the brain, on creatine, for energy provision during high-intensity activity. From a broader, methodological perspective, our data highlight the importance of considering external factors, such as prior exercise, in standardisation protocols for repeated MRS studies of creatine concentrations in the human brain. Determining the response of creatine concentrations in brain to other types of exercise and, indeed, other stimuli, could provide additional insight into the dependence of the brain on creatine during periods of increased metabolic demand, supporting the development of therapeutic strategies to support brain function.
Read CV Jedd PrattECSS Paris 2023: OP-PN35