| 1. |
- Calbet, José A L, et al.
(författare)
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Limitations to oxygen transport and utilisation during sprint exercise in humans : evidence for a functional reserve in muscle O2 diffusing capacity.
- 2015
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Ingår i: Journal of Physiology. - 0022-3751 .- 1469-7793. ; 593:20, s. 4649-4664
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Tidskriftsartikel (refereegranskat)abstract
- KEY POINTS SUMMARY: Severe acute hypoxia reduces sprint performance. Muscle VO2 during sprint exercise in normoxia is not limited by O2 delivery, O2 off-loading from haemoglobin or structure-dependent diffusion constraints in the skeletal muscle of young healthy men. A large functional reserve in muscle O2 diffusing capacity exists and remains available at exhaustion during exercise in normoxia, which is recruited during exercise in hypoxia. During whole-body incremental exercise to exhaustion in severe hypoxia leg VO2 is primarily dependent on convective O2 delivery and less limited by diffusion constraints than previously thought. The kinetics of O2 off-loading from haemoglobin does not limit VO2 peak in hypoxia. Our results indicate that the limitation to VO2 during short sprints resides in mechanisms regulating mitochondrial respiration.ABSTRACT: To determine the contribution of convective and diffusive limitations to VO2 peak during exercise in humans oxygen transport and haemodynamics were measured in eleven men (22 ± 2 years) during incremental (IE) and 30-s all-out sprints (Wingate test, WgT), in normoxia (Nx, PI O2 :143 mmHg) and hypoxia (Hyp, PI O2 :73 mmHg). Carboxyhaemoglobin (COHb) was increased to 6-7% before both WgTs to left-shift the oxyhaemoglobin dissociation curve. Leg VO2 was measured by the Fick method, and leg blood flow (BF) with thermodilution and muscle O2 diffusing capacity (DMO2 ) was calculated. In the WgT mean power output, leg BF, leg O2 delivery and leg VO2 were 7, 5, 28 and 23% lower in Hyp than Nx (P < 0.05), however, peak WgT DMO2 was higher in hypoxia (51.5 ± 9.7) than Nx (20.5 ± 3.0 ml min(-1) mmHg(-1) , P < 0.05). Despite a similar PaO2 (33.3 ± 2.4 and 34.1 ± 3.3 mmHg), mean capillary PO2 (16.7 ± 1.2 and 17.1 ± 1.6 mmHg), and peak perfusion during IE and WgT in Hyp, DMO2 and leg VO2 were 12 and 14% higher during WgT than IE in Hyp (both, P < 0.05). DMO2 was apparently insensitive to COHb (COHb: 0.7 vs 7%, in IE Hyp and WgT Hyp). At exhaustion, the Y equilibration index was well above 1.0 in both conditions, reflecting greater convective than diffusive limitation to the O2 transfer both in Nx and Hyp. In conclusion, muscle VO2 during sprint exercise is not limited by O2 delivery, the O2 off-loading from haemoglobin or structure-dependent diffusion constraints in the skeletal muscle. These findings reveal a remarkable functional reserve in muscle O2 diffusing capacity. This article is protected by copyright. All rights reserved.
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| 2. |
- Cardinale, Daniele A., 1982-, et al.
(författare)
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Superior Intrinsic Mitochondrial Respiration in Women Than in Men.
- 2018
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Sexual dimorphism is apparent in humans, however, to date no studies have investigated mitochondrial function focusing on intrinsic mitochondrial respiration (i.e., mitochondrial respiration for a given amount of mitochondrial protein) and mitochondrial oxygen affinity (p50mito) in relation to biological sex in human. A skeletal muscle biopsy was donated by nine active women, and ten men matched for maximal oxygen consumption (VO2max) and by nine endurance trained men. Intrinsic mitochondrial respiration, assessed in isolated mitochondria, was higher in women compared to men when activating complex I (CIP) and complex I+II (CI+IIP) (p < 0.05), and was similar to trained men (CIP, p = 0.053; CI+IIP, p = 0.066). Proton leak and p50mito were higher in women compared to men independent of VO2max. In conclusion, significant novel differences in mitochondrial oxidative function, intrinsic mitochondrial respiration and p50mito exist between women and men. These findings may represent an adaptation in the oxygen cascade in women to optimize muscle oxygen uptake to compensate for a lower oxygen delivery during exercise.
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| 3. |
- Larsen, Filip J, 1977-, et al.
(författare)
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Mitochondrial oxygen affinity increases after sprint interval training and is related to the improvement in peak oxygen uptake.
- 2020
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Ingår i: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 229:3
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The body responds to exercise training by profound adaptations throughout the cardiorespiratory and muscular systems, which may result in improvements in maximal oxygen consumption (VO2 peak) and mitochondrial capacity. By convenience, mitochondrial respiration is often measured at supra-physiological oxygen levels, an approach that ignores any potential regulatory role of mitochondrial affinity for oxygen (p50mito ) at physiological oxygen levels.METHODS: In this study, we examined the p50mito of mitochondria isolated from the Vastus lateralis and Triceps brachii in 12 healthy volunteers before and after a training intervention with 7 sessions of sprint interval training using both leg cycling and arm cranking. The changes in p50mito were compared to changes in whole-body VO2 peak.RESULTS: We here show that p50mito is similar in isolated mitochondria from the Vastus (40 ± 3.8 Pa) compared to Triceps (39 ± 3.3) but decreases (mitochondrial oxygen affinity increases) after 7 sessions of sprint interval training (to 26 ± 2.2 Pa in Vastus and 22 ± 2.7 Pa in Triceps, both p<0.01). The change in VO2 peak modeled from changes in p50mito was correlated to actual measured changes in VO2 peak (R2 =0.41, p=0.002).CONCLUSION: Together with mitochondrial respiratory capacity, p50mito is a critical factor when measuring mitochondrial function, it can decrease with sprint interval training and should be considered in the integrative analysis of the oxygen cascade from lung to mitochondria.
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| 4. |
- Perez-Valera, Mario, et al.
(författare)
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Angiotensin-Converting Enzyme 2 (SARS-CoV-2 receptor) expression in human skeletal muscle
- 2021
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 31:12, s. 2249-2258
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Tidskriftsartikel (refereegranskat)abstract
- The study aimed to determine the levels of skeletal muscle Angiotensin-Converting Enzyme 2 (ACE2, the SARS-CoV-2 receptor) protein expression in men and women and assess whether ACE2 expression in skeletal muscle is associated with cardiorespiratory fitness and adiposity. The level of ACE2 in vastus lateralis muscle biopsies collected in previous studies from 170 men (age:19-65 yrs, weight:56-137 kg, BMI:23-44) and 69 women (age:18-55 yrs, weight:41-126 kg, BMI:22-39) was analysed in duplicate by western blot. VO2max was determined by ergospirometry and body composition by DXA. ACE2 protein expression was 1.8-fold higher in women than men (p=0.001, n=239). This sex difference disappeared after accounting for the percentage of body fat (fat %), VO2max per kg of legs lean mass (VO2max-LLM) and age (p=0.47). Multiple regression analysis showed that the fat % (β=0.47) is the main predictor of the variability in ACE2 protein expression in skeletal muscle, explaining 5.2 % of the variance. VO2max-LLM had also predictive value (β=0.09). There was a significant fat % by VO2max-LLM interaction, such that for subjects with low fat %, VO2max-LLM was positively associated with ACE2 expression while as fat % increased the slope of the positive association between VO2max-LLM and ACE2 was reduced. In conclusion, women express higher amounts of ACE2 in their skeletal muscles than men. This sexual dimorphism is mainly explained by sex differences in fat % and cardiorespiratory fitness. The percentage of body fat is the main predictor of the variability in ACE2 protein expression in human skeletal muscle.
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| 5. |
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| 6. |
- Galvan-Alvarez, Victor, et al.
(författare)
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Antioxidant enzymes and Nrf2/Keap1 in human skeletal muscle: Influence of age, sex, adiposity and aerobic fitness
- 2023
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Ingår i: Free Radical Biology & Medicine. - : Elsevier Inc.. - 0891-5849 .- 1873-4596. ; 209:Part 2, s. 282-291
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Tidskriftsartikel (refereegranskat)abstract
- Whether a higher aerobic fitness is associated with increased expression of antioxidant enzymes and their regulatory factors in skeletal muscle remains unknown. Although oestrogens could promote a higher antioxidant capacity in females, it remains unknown whether a sex dimorphism exists in humans regarding the antioxidant capacity of skeletal muscle. Thus, the aim was to determine the protein expression levels of the antioxidant enzymes SOD1, SOD2, catalase and glutathione reductase (GR) and their regulatory factors Nrf2 and Keap1 in 189 volunteers (120 males and 69 females) to establish whether sex differences exist and how age, VO2max and adiposity influence these. For this purpose, vastus lateralis muscle biopsies were obtained in all participants under resting and unstressed conditions. No significant sex differences in Nrf2, Keap1, SOD1, SOD2, catalase and GR protein expression levels were observed after accounting for VO2max, age and adiposity differences. Multiple regression analysis indicates that the VO2max in mL.kg LLM−1.min−1can be predicted from the levels of SOD2, Total Nrf2 and Keap1 (R = 0.58, P < 0.001), with SOD2 being the main predictor explaining 28 % of variance in VO2max, while Nrf2 and Keap1 explained each around 3 % of the variance. SOD1 protein expression increased with ageing in the whole group after accounting for differences in VO2max and body fat percentage. Overweight and obesity were associated with increased pSer40-Nrf2, pSer40-Nrf2/Total Nrf2 ratio and SOD1 protein expression levels after accounting for differences in age and VO2max. Overall, at the population level, higher aerobic fitness is associated with increased basal expression of muscle antioxidant enzymes, which may explain some of the benefits of regular exercise.
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| 7. |
- Perez-Suarez, Ismael, et al.
(författare)
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Severe energy deficit upregulates leptin receptors, leptin signaling, and PTP1B in human skeletal muscle
- 2017
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 123:5, s. 1276-1287
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Tidskriftsartikel (refereegranskat)abstract
- In obesity, leptin receptors (OBR) and leptin signaling in skeletal muscle are downregulated. To determine whether OBR and leptin signaling are upregulated with a severe energy deficit, 15 overweight men were assessed before the intervention (PRE), after 4 days of caloric restriction (3.2 kcal·kg body wt-1·day-1) in combination with prolonged exercise (CRE; 8 h walking + 45 min single-arm cranking/day) to induce an energy deficit of ~5,500 kcal/day, and following 3 days of control diet (isoenergetic) and reduced exercise (CD). During CRE, the diet consisted solely of whey protein (n = 8) or sucrose (n = 7; 0.8 g·kg body wt-1·day-1). Muscle biopsies were obtained from the exercised and the nonexercised deltoid muscles and from the vastus lateralis. From PRE to CRE, serum glucose, insulin, and leptin were reduced. OBR expression was augmented in all examined muscles associated with increased maximal fat oxidation. Compared with PRE, after CD, phospho-Tyr1141, phospho-Tyr985OBR, JAK2, and phospho- Tyr1007/1008JKK2protein expression were increased in all muscles, whereas STAT3 and phospho-Tyr705STAT3 were increased only in the arms. The expression of protein tyrosine phosphatase 1B (PTP1B) in skeletal muscle was increased by 18 and 45% after CRE and CD, respectively (P < 0.05). Suppressor of cytokine signaling 3 (SOCS3) tended to increase in the legs and decrease in the arm muscles (ANOVA interaction: P < 0.05). Myosin heavy chain I isoform was associated with OBR protein expression (r-=0.75), phospho- Tyr985OBR (r = 0.88), and phospho-Tyr705STAT3/STAT3 (r = 0.74). In summary, despite increased PTP1B expression, skeletal muscle OBR and signaling are upregulated by a severe energy deficit with greater response in the arm than in the legs likely due to SOCS3 upregulation in the leg muscles NEW & NOTEWORTHY This study shows that the skeletal muscle leptin receptors and their corresponding signaling cascade are upregulated in response to a severe energy deficit, contributing to increase maximal fat oxidation. The responses are more prominent in the arm muscles than in the legs but partly blunted by whey protein ingestion and high volume of exercise. This occurs despite an increase of protein tyrosine phosphatase 1B protein expression, a known inhibitor of insulin and leptin signaling.
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| 8. |
- Blomstrand, Eva, et al.
(författare)
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Exercise training induces similar elevations in the activity of oxoglutarate dehydrogenase and peak oxygen uptake in the human quadriceps muscle.
- 2011
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Ingår i: Pflügers Archiv. - : Springer Science and Business Media LLC. - 0031-6768 .- 1432-2013. ; 462:2, s. 257-65
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Tidskriftsartikel (refereegranskat)abstract
- During exercise involving a small muscle mass, peak oxygen uptake is thought to be limited by peripheral factors, such as the degree of oxygen extraction from the blood and/or mitochondrial oxidative capacity. Previously, the maximal activity of the Krebs cycle enzyme oxoglutarate dehydrogenase has been shown to provide a quantitative measure of maximal oxidative metabolism, but it is not known whether the increase in this activity after a period of training reflects the elevation in peak oxygen consumption. Fourteen subjects performed one-legged knee extension exercise for 5-7 weeks, while the other leg remained untrained. Thereafter, the peak oxygen uptake by the quadriceps muscle was determined for both legs, and muscle biopsies were taken for assays of maximal enzyme activities (at 25°C). The peak oxygen uptake was 26% higher in the trained than in the untrained muscle (395 vs. 315 ml min(-1) kg(-1), respectively; P<0.01). The maximal activities of the Krebs cycle enzymes in the trained and untrained muscle were as follows: citrate synthase, 22.4 vs. 18.2 μmol min(-1) g(-1) (23%, P<0.05); oxoglutarate dehydrogenase, 1.88 vs. 1.54 μmol min(-1) g(-1) (22%, P<0.05); and succinate dehydrogenase, 3.88 vs. 3.28 μmol min(-1) g(-1) (18%, P<0.05). The difference between the trained and untrained muscles with respect to peak oxygen uptake (80 ml min(-1) kg(-1)) corresponded to a flux through the Krebs cycle of 1.05 μmol min(-1) g(-1), and the corresponding difference in oxoglutarate dehydrogenase activity (at 38°C) was 0.83 μmol min(-1) g(-1). These parallel increases suggest that there is no excess mitochondrial capacity during maximal exercise with a small muscle mass.
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| 9. |
- Calbet, Jose A L, et al.
(författare)
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Assessment of cardiac output with transpulmonary thermodilution during exercise in humans.
- 2015
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 118:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- The accuracy and reproducibility of transpulmonary thermodilution (TPTd) to assess cardiac output (Q) in exercising men was determined using indocyanine green (ICG) dilution as a reference method. TPTd has been utilized for the assessment of Q and preload indices of global end-diastolic volume (GEDV) and intrathoracic blood volume (ITBV), as well as extravascular lung water (EVLW) in resting humans. It remains unknown if this technique is also accurate and reproducible during exercise. Sixteen healthy men underwent catheterization of the right femoral vein (for iced saline injection), an antecubital vein (ICG injection) and femoral artery (thermistor) to determine their Q by TPTd and [ICG] during incremental 1 and 2-legged pedaling on a cycle ergometer, and combined arm cranking with leg pedaling to exhaustion. There was a close relationship between Td-Q and ICG-Q (r=0.95, n=151, SEE: 1.452 L/min, P<0.001; mean difference of 0.06 L/min; limits of agreement -2.98 to 2.86 L/min), and TPTd-Q and ICG-Q increased linearly with VO2 with similar intercepts and slopes. Both methods had mean coefficients of variation (CV) close to 5% for Q, GEDV and ITBV. The mean CV of EVLW, assessed with both indicators (ICG and thermal) was 17%, and was sensitive enough as to detect a reduction in EVLW of 107 ml when changing from resting supine to upright exercise. In summary, transpulmonary thermodilution with bolus injection into the femoral vein is an accurate and reproducible method to assess cardiac output during exercise in humans.
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| 10. |
- Calbet, Jose A. L., et al.
(författare)
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Exercise Preserves Lean Mass and Performance during Severe Energy Deficit : The Role of Exercise Volume and Dietary Protein Content
- 2017
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The loss of fat-free mass (FFM) caused by very-low-calorie diets (VLCD) can be attenuated by exercise. The aim of this study was to determine the role played by exercise and dietary protein content in preserving the lean mass and performance of exercised and non-exercised muscles, during a short period of extreme energy deficit (similar to 23 MJ deficit/day). Fifteen overweight men underwent three consecutive experimental phases: baseline assessment (PRE), followed by 4 days of caloric restriction and exercise (CRE) and then 3 days on a control diet combined with reduced exercise (CD). During CRE, the participants ingested a VLCD and performed 45 min of one-arm cranking followed by 8 h walking each day. The VLCD consisted of 0.8 g/kg body weight/day of either whey protein (PRO, n = 8) or sucrose (SU, n = 7). FFM was reduced after CRE (P < 0.001), with the legs and the exercised arm losing proportionally less FFM than the control arm [57% (P < 0.05) and 29% (P = 0.05), respectively]. Performance during leg pedaling, as reflected by the peak oxygen uptake and power output (Wpeak), was reduced after CRE by 15 and 12%, respectively (P < 0.05), and recovered only partially after CD. The deterioration of cycling performance was more pronounced in the whey protein than sucrose group (P < 0.05). Wpeak during arm cranking was unchanged in the control arm, but improved in the contralateral arm by arm cranking. There was a linear relationship between the reduction in whole-body FFM between PRE and CRE and the changes in the cortisol/free testosterone ratio (C/FT), serum isoleucine, leucine, tryptophan, valine, BCAA, and EAA (r = -0.54 to -0.71, respectively, P < 0.05). C/FT tended to be higher in the PRO than the SU group following CRE (P = 0.06). In conclusion, concomitant low-intensity exercise such as walking or arm cranking even during an extreme energy deficit results in remarkable preservation of lean mass. The intake of proteins alone may be associated with greater cortisol/free testosterone ratio and is not better than the ingestion of only carbohydrates for preserving FFM and muscle performance in interventions of short duration.
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