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1.
  • Watson, Hunna J., et al. (författare)
  • Common Genetic Variation and Age of Onset of Anorexia Nervosa
  • 2022
  • Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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2.
  • Boushel, Robert, et al. (författare)
  • Maintained peak leg and pulmonary VO2 despite substantial reduction in muscle mitochondrial capacity.
  • 2015
  • Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 25:Suppl 4, s. 135-143
  • Tidskriftsartikel (refereegranskat)abstract
    • We recently reported the circulatory and muscle oxidative capacities of the arm after prolonged low-intensity skiing in the arctic (Boushel et al., 2014). In the present study, leg VO2 was measured by the Fick method during leg cycling while muscle mitochondrial capacity was examined on a biopsy of the vastus lateralis in healthy volunteers (7 male, 2 female) before and after 42 days of skiing at 60% HR max. Peak pulmonary VO2 (3.52 ± 0.18 L.min(-1) pre vs 3.52 ± 0.19 post) and VO2 across the leg (2.8 ± 0.4L.min(-1) pre vs 3.0 ± 0.2 post) were unchanged after the ski journey. Peak leg O2 delivery (3.6 ± 0.2 L.min(-1) pre vs 3.8 ± 0.4 post), O2 extraction (82 ± 1% pre vs 83 ± 1 post), and muscle capillaries per mm(2) (576 ± 17 pre vs 612 ± 28 post) were also unchanged; however, leg muscle mitochondrial OXPHOS capacity was reduced (90 ± 3 pmol.sec(-1) .mg(-1) pre vs 70 ± 2 post, P < 0.05) as was citrate synthase activity (40 ± 3 μmol.min(-1) .g(-1) pre vs 34 ± 3 vs P < 0.05). These findings indicate that peak muscle VO2 can be sustained with a substantial reduction in mitochondrial OXPHOS capacity. This is achieved at a similar O2 delivery and a higher relative ADP-stimulated mitochondrial respiration at a higher mitochondrial p50. These findings support the concept that muscle mitochondrial respiration is submaximal at VO2max , and that mitochondrial volume can be downregulated by chronic energy demand.
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3.
  • Blackwood, Sarah J, et al. (författare)
  • Extreme Variations in Muscle Fiber Composition Enable Detection of Insulin Resistance and Excessive Insulin Secretion.
  • 2022
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 107:7, s. e2729-e2737
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Muscle fiber composition is associated with peripheral insulin action.OBJECTIVE: We investigated whether extreme differences in muscle fiber composition are associated with alterations in peripheral insulin action and secretion in young, healthy subjects who exhibit normal fasting glycemia and insulinemia.METHODS: Relaxation time following a tetanic contraction was used to identify subjects with a high or low expression of type I muscle fibers: group I (n=11), area occupied by type I muscle fibers = 61.0 ± 11.8%; group II (n=8), type I area = 36.0 ± 4.9% (P<0.001). Biopsies were obtained from the vastus lateralis muscle and analyzed for mitochondrial respiration on permeabilized fibers, muscle fiber composition and capillary density. An intravenous glucose tolerance test was performed and indices of glucose tolerance, insulin sensitivity and secretion were determined.RESULTS: Glucose tolerance was similar between groups, whereas whole-body insulin sensitivity was decreased by ~50% in group II vs group I (P=0.019). First phase insulin release (area under the insulin curve during 10 min after glucose infusion) was increased by almost 4-fold in group II vs I (P=0.01). Whole-body insulin sensitivity was correlated with % area occupied by type I fibers (r=0.54; P=0.018) and capillary density in muscle (r=0.61; P=0.005), but not with mitochondrial respiration. Insulin release was strongly related to % area occupied by type II fibers (r=0.93; P<0.001).CONCLUSIONS: Assessment of muscle contractile function in young healthy subjects may prove useful in identifying individuals with insulin resistance and enhanced glucose stimulated insulin secretion prior to onset of clinical manifestations.
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4.
  • Blackwood, Sarah J, et al. (författare)
  • Insulin resistance after a 3-day fast is associated with an increased capacity of skeletal muscle to oxidize lipids.
  • 2023
  • Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 324:5, s. E390-E401
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a debate on whether lipid-mediated insulin resistance derives from an increased or decreased capacity of muscle to oxidize fats. Here we examine the involvement of muscle fiber composition in the metabolic responses to a 3-day fast (starvation, which results in increases in plasma lipids and insulin resistance) in two groups of healthy young subjects: 1, area occupied by type I fibers = 61.0 ± 11.8%; 2, type I area = 36.0 ± 4.9% (P<0.001). Muscle biopsies and intravenous glucose tolerance tests were performed after an overnight fast and after starvation. Biopsies were analyzed for muscle fiber composition and mitochondrial respiration. Indices of glucose tolerance and insulin sensitivity were determined. Glucose tolerance was similar in both groups after an overnight fast and deteriorated to a similar degree in both groups after starvation. In contrast, whole-body insulin sensitivity decreased markedly after starvation in group 1 (P<0.01), whereas the decrease in group 2 was substantially smaller (P=0.06). Non-esterified fatty acids and β-hydroxybutyrate levels in plasma after an overnight fast were similar between groups and increased markedly and comparably in both groups after starvation, demonstrating similar degrees of lipid load. The capacity of permeabilized muscle fibers to oxidize lipids was significantly higher in group 1 vs. 2, whereas there was no significant difference in pyruvate oxidation between groups. The data demonstrate that loss of whole-body insulin sensitivity after short-term starvation is a function of muscle fiber composition and is associated with an elevated rather than a diminished capacity of muscle to oxidize lipids.
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5.
  • Cardinale, Daniele A., 1982-, et al. (författare)
  • Muscle mass and inspired oxygen influence oxygen extraction at maximal exercise : role of mitochondrial oxygen affinity.
  • 2019
  • Ingår i: Acta Physiologica. - : Wiley-Blackwell. - 1748-1708 .- 1748-1716. ; 225:1
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM:We examined the Fick components together with mitochondrial O2 affinity (p50mito ) in defining O2 extraction and O2 uptake during exercise with large and small muscle mass during normoxia (NORM) and hyperoxia (HYPER).METHODS:Seven individuals performed two incremental exercise tests to exhaustion on a bicycle ergometer (BIKE) and two on a one-legged knee extension ergometer (KE) in NORM or HYPER. Leg blood flow and VO2 were determined by thermodilution and the Fick method. Maximal ADP-stimulated mitochondrial respiration (OXPHOS) and p50mito were measured ex vivo in isolated mitochondria. Mitochondrial excess capacity in the leg was determined from OXPHOS in permeabilized fibers and muscle mass measured with magnetic resonance imaging in relation to peak leg O2 delivery.RESULTS:The ex vivo p50mito increased from 0.06±0.02 to 0.17±0.04 kPa with varying substrate supply and O2 flux rates from 9.84±2.91 to 16.34±4.07 pmol O2 ·s-1 ·μg-1 respectively. O2 extraction decreased from 83% in BIKE to 67% in KE as a function of a higher O2 delivery, and lower mitochondrial excess capacity. There was a significant relationship between O2 extraction and mitochondrial excess capacity and p50mito that was unrelated to blood flow and mean transit time.CONCLUSION:O2 extraction varies with mitochondrial respiration rate, p50mito and O2 delivery. Mitochondrial excess capacity maintains a low p50mito which enhances O2 diffusion from microvessels to mitochondria during exercise. This article is protected by copyright. All rights reserved.
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6.
  • Flockhart, Mikael, et al. (författare)
  • Reduced glucose tolerance and insulin sensitivity after prolonged exercise in endurance athletes.
  • 2023
  • Ingår i: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 238:4
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: The purpose of this study was to 1. investigate if glucose tolerance is affected after one acute bout of different types of exercise; 2. assess if potential differences between two exercise paradigms are related to changes in mitochondrial function; and 3. determine if endurance athletes differ from nonendurance-trained controls in their metabolic responses to the exercise paradigms.METHODS: Nine endurance athletes (END) and eight healthy nonendurance-trained controls (CON) were studied. Oral glucose tolerance tests (OGTT) and mitochondrial function were assessed on three occasions: in the morning, 14 h after an overnight fast without prior exercise (RE), as well as after 3 h of prolonged continuous exercise at 65% of VO2 max (PE) or 5 × 4 min at ~95% of VO2 max (HIIT) on a cycle ergometer.RESULTS: Glucose tolerance was markedly reduced in END after PE compared with RE. END also exhibited elevated fasting serum FFA and ketones levels, reduced insulin sensitivity and glucose oxidation, and increased fat oxidation during the OGTT. CON showed insignificant changes in glucose tolerance and the aforementioned measurements compared with RE. HIIT did not alter glucose tolerance in either group. Neither PE nor HIIT affected mitochondrial function in either group. END also exhibited increased activity of 3-hydroxyacyl-CoA dehydrogenase activity in muscle extracts vs. CON.CONCLUSION: Prolonged exercise reduces glucose tolerance and increases insulin resistance in endurance athletes the following day. These findings are associated with an increased lipid load, a high capacity to oxidize lipids, and increased fat oxidation.
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7.
  • Flockhart, Mikael, et al. (författare)
  • THREE HOURS OF MODERATE INTENSITY EXERCISE TRAINING REDUCES GLUCOSE TOLERANCE IN ENDURANCE TRAINED ATHLETES
  • 2022
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • BACKGROUNDIt is well accepted that exercise training improves glucose uptake and insulin sensitivity, and that endurance trained athletes in general show a high capacity for these parameters and excellent metabolic control. However, some studies fail to observe positive effects on glucose regulation in healthy, trained subjects the day after exercise. These, often unexpected, results have been postulated to be caused by excessive training loads, muscle damage, energy deficit, differences in glucose uptake in the exercised and non-exercised musculature and a metabolic interaction through increased fatty acid metabolism which suppresses glucose oxidation and uptake. The mode or volume of exercise that can lead to glucose intolerance in trained athletes as well as mechanistic insights and its relevance for health and performance are, however, not fully understood.AIMWe studied the metabolic response to a glucose load the day after a session of high intensity interval training (HIIT) or three hours of continuous exercise (3h) in endurance trained athletes and compared the results with measurements during rest.METHODNine endurance trained athletes (5 females, 4 males) underwent oral glucose tolerance tests (OGTT) after rest and ~14 hours after exercise on a cycle ergometer (HIIT 5x4 minutes at ~95% of VO2max or 3h at 65% of VO2max). Venous blood was sampled at 15-minute intervals for 120 minutes and concentrations of glucose, insulin, free fatty acids (FFA) and ketones (β-hydroxybutyrate) were measured. Statistical analysis was performed using a RM one-way ANOVA with the Giesser-Greenhouse correction and Dunnett’s test was used to compare the exercise conditions to the resting condition.RESULTSThe area under the curve (AUC) during the OGTT increased greatly after 3h (668±124 mM · min) (p<0.01) compared to rest (532±89) but was found to be unchanged after HIIT (541±96). Resting values of FFA and ketones were increased after 3h (p<0.01 and p<0.05, respectively) but not after HIIT. Insulin was found to be unaltered during all conditions.CONCLUSIONS AND RELEVANCEHere, we show manifestation of glucose intolerance in endurance trained athletes together with concomitant increases in plasma concentrations of FFA and ketones the day after a session of prolonged exercise training but not after HIIT. This could be a protective response for securing glucose delivery to the brain and therefore have a positive effect on endurance. It also has the potential to reduce the recovery of glycogen depots, glucose uptake during exercise and performance at higher work rates.
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9.
  • Larsen, Filip J, et al. (författare)
  • High-intensity sprint training inhibits mitochondrial respiration through aconitase inactivation
  • 2016
  • Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 30:1, s. 417-427
  • Tidskriftsartikel (refereegranskat)abstract
    • Intense exercise training is a powerful stimulus that activates mitochondrial biogenesis pathways and thus increases mitochondrial density and oxidative capacity. Moderate levels of reactive oxygen species (ROS) during exercise are considered vital in the adaptive response, but high ROS production is a serious threat to cellular homeostasis. Although biochemical markers of the transition from adaptive to maladaptive ROS stress are lacking, it is likely mediated by redox sensitive enzymes involved in oxidative metabolism. One potential enzyme mediating such redox sensitivity is the citric acid cycle enzyme aconitase. In this study, we examined biopsy specimens of vastus lateralis and triceps brachii in healthy volunteers, together with primary human myotubes. An intense exercise regimen inactivated aconitase by 55-72%, resulting in inhibition of mitochondrial respiration by 50-65%. In the vastus, the mitochondrial dysfunction was compensated for by a 15-72% increase in mitochondrial proteins, whereas H2O2 emission was unchanged. In parallel with the inactivation of aconitase, the intermediary metabolite citrate accumulated and played an integral part in cellular protection against oxidative stress. In contrast, the triceps failed to increase mitochondrial density, and citrate did not accumulate. Instead, mitochondrial H2O2 emission was decreased to 40% of the pretraining levels, together with a 6-fold increase in protein abundance of catalase. In this study, a novel mitochondrial stress response was highlighted where accumulation of citrate acted to preserve the redox status of the cell during periods of intense exercise.
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10.
  • Larsen, Filip J, 1977-, et al. (författare)
  • Mitochondrial oxygen affinity increases after sprint interval training and is related to the improvement in peak oxygen uptake.
  • 2020
  • Ingår i: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 229:3
  • 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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11.
  • Zinner, Christoph, et al. (författare)
  • The Physiological Mechanisms of Performance Enhancement with Sprint Interval Training Differ between the Upper and Lower Extremities in Humans
  • 2016
  • Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 7:SEP
  • Tidskriftsartikel (refereegranskat)abstract
    • To elucidate the mechanisms underlying the differences in adaptation of arm and leg muscles to sprint training, over a period of 11 days 16 untrained men performed six sessions of 4-6 x 30-s all-out sprints (SIT) with the legs and arms, separately, with a 1-h interval of recovery. Limb-specific VO(2)peak, sprint performance (two 30-s Wingate tests with 4-min recovery), muscle efficiency and time-trial performance (TT, 5-min all-out) were assessed and biopsies from the m. vastus lateralis and m. triceps brachii taken before and after training. VO(2)peak and Wmax increased 3-11% after training, with a more pronounced change in the arms (P < 0.05). Gross efficiency improved for the arms (+8.8%, P < 0.05), but not the legs (-0.6%). Wingate peak and mean power outputs improved similarly for the arms and legs, as did TT performance. After training, VO2 during the two Wingate tests was increased by 52 and 6% for the arms and legs, respectively (P < 0.001). In the case of the arms, VO2 was higher during the first than second Wingate test (64 vs. 44%, P < 0.05). During the TT, relative exercise intensity, HR, VO2, VCO2, V-E, and V-t were all lower during arm-cranking than leg-pedaling, and oxidation of fat was minimal, remaining so after training. Despite the higher relative intensity, fat oxidation was 70% greater during leg-pedaling (P = 0.017). The aerobic energy contribution in the legs was larger than for the arms during the Wingate tests, although VO2 for the arms was enhanced more by training, reducing the O-2 deficit after SIT. The levels of muscle glycogen, as well as the myosin heavy chain composition were unchanged in both cases, while the activities of 3-hydroxyacyl-CoA-dehydrogenase and citrate synthase were elevated only in the legs and capillarization enhanced in both limbs. Multiple regression analysis demonstrated that the variables that predict TT performance differ for the arms and legs. The primary mechanism of adaptation to SIT by both the arms and legs is enhancement of aerobic energy production. However, with their higher proportion of fast muscle fibers, the arms exhibit greater plasticity.
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14.
  • Cardinale, Daniele A., 1982-, et al. (författare)
  • Enhanced Skeletal Muscle Oxidative Capacity and Capillary-to-Fiber Ratio Following Moderately Increased Testosterone Exposure in Young Healthy Women
  • 2020
  • Ingår i: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Recently, it was shown that exogenously administered testosterone enhances endurance capacity in women. In this study, our understanding on the effects of exogenous testosterone on key determinants of oxygen transport and utilization in skeletal muscle is expanded.Methods: In a double-blinded, randomized, placebo-controlled trial, 48 healthy active women were randomized to 10 weeks of daily application of 10 mg of testosterone cream or placebo. Before and after the intervention, VO2 max, body composition, total hemoglobin (Hb) mass and blood volumes were assessed. Biopsies from the vastus lateralis muscle were obtained before and after the intervention to assess mitochondrial protein abundance, capillary density, capillary-to-fiber (C/F) ratio, and skeletal muscle oxidative capacity.Results: Maximal oxygen consumption per muscle mass, Hb mass, blood, plasma and red blood cell volumes, capillary density, and the abundance of mitochondrial protein levels (i.e., citrate synthase, complexes I, II, III, IV-subunit 2, IV-subunit 4, and V) were unchanged by the intervention. However, the C/F ratio, specific mitochondrial respiratory flux activating complex I and linked complex I and II, uncoupled respiration and electron transport system capacity, but not leak respiration or fat respiration, were significantly increased following testosterone administration compared to placebo.Conclusion: This study provides novel insights into physiological actions of increased testosterone exposure on key determinants of oxygen diffusion and utilization in skeletal muscle of women. Our findings show that higher skeletal muscle oxidative capacity coupled to higher C/F ratio could be major contributing factors that improve endurance performance following moderately increased testosterone exposure.
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15.
  • Cardinale, Daniele A., 1982-, et al. (författare)
  • Influence of Hyperoxic-Supplemented High-Intensity Interval Training on Hemotological and Muscle Mitochondrial Adaptations in Trained Cyclists.
  • 2019
  • Ingår i: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Hyperoxia (HYPER) increases O2 carrying capacity resulting in a higher O2 delivery to the working muscles during exercise. Several lines of evidence indicate that lactate metabolism, power output, and endurance are improved by HYPER compared to normoxia (NORM). Since HYPER enables a higher exercise power output compared to NORM and considering the O2 delivery limitation at exercise intensities near to maximum, we hypothesized that hyperoxic-supplemented high-intensity interval training (HIIT) would upregulate muscle mitochondrial oxidative capacity and enhance endurance cycling performance compared to training in normoxia. Methods: 23 trained cyclists, age 35.3 ± 6.4 years, body mass 75.2 ± 9.6 kg, height 179.8 ± 7.9 m, and VO2max 4.5 ± 0.7 L min-1 performed 6 weeks polarized and periodized endurance training on a cycle ergometer consisting of supervised HIIT sessions 3 days/week and additional low-intensity training 2 days/week. Participants were randomly assigned to either HYPER (FIO2 0.30; n = 12) or NORM (FIO2 0.21; n = 11) breathing condition during HIIT. Mitochondrial respiration in permeabilized fibers and isolated mitochondria together with maximal and submaximal VO2, hematological parameters, and self-paced endurance cycling performance were tested pre- and posttraining intervention. Results: Hyperoxic training led to a small, non-significant change in performance compared to normoxic training (HYPER 6.0 ± 3.7%, NORM 2.4 ± 5.0%; p = 0.073, ES = 0.32). This small, beneficial effect on the self-paced endurance cycling performance was not explained by the change in VO2max (HYPER 1.1 ± 3.8%, NORM 0.0 ± 3.7%; p = 0.55, ES = 0.08), blood volume and hemoglobin mass, mitochondrial oxidative phosphorylation capacity (permeabilized fibers: HYPER 27.3 ± 46.0%, NORM 16.5 ± 49.1%; p = 0.37, ES = 3.24 and in isolated mitochondria: HYPER 26.1 ± 80.1%, NORM 15.9 ± 73.3%; p = 0.66, ES = 0.51), or markers of mitochondrial content which were similar between groups post intervention. Conclusions: This study showed that 6 weeks hyperoxic-supplemented HIIT led to marginal gain in cycle performance in already trained cyclists without change in VO2max, blood volume, hemoglobin mass, mitochondrial oxidative phosphorylation capacity, or exercise efficiency. The underlying mechanisms for the potentially meaningful performance effects of hyperoxia training remain unexplained and may raise ethical questions for elite sport.
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16.
  • Cardinale, Daniele A, et al. (författare)
  • Reliability of maximal mitochondrial oxidative phosphorylation in permeabilized fibers from the vastus lateralis employing high-resolution respirometry.
  • 2018
  • Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 6:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose was to assess the impact of various factors on methodological errors associated with measurement of maximal oxidative phosphorylation (OXPHOS) in human skeletal muscle determined by high-resolution respirometry in saponin-permeabilized fibers. Biopsies were collected from 25 men to assess differences in OXPHOS between two muscle bundles and to assess the correlation between OXPHOS and the wet weight of the muscle bundle. Biopsies from left and right thighs of another five subjects were collected on two occasions to compare limbs and time-points. A single muscle specimen was used to assess effects of the anesthetic carbocaine and the influence of technician. The difference in OXPHOS between two fiber-bundles from the same biopsy exhibited a standard error of measurement (SEM) of 10.5 pmol · s-1  · mg-1 and a coefficient of variation (CV) of 15.2%. The differences between left and right thighs and between two different time-points had SEMs of 9.4 and 15.2 pmol · s-1  · mg-1 and CVs of 23.9% and 33.1%, respectively. The average (±SD) values obtained by two technicians monitoring different bundles of fibers from the same biopsy were 31.3 ± 7.1 and 26.3 ± 8.1 pmol · s-1  · mg-1 . The time that elapsed after collection of the biopsy (up to a least 5 h in preservation medium), wet weight of the bundle (from 0.5 to 4.5 mg) and presence of an anesthetic did not influence OXPHOS. The major source of variation in OXPHOS measurements is the sample preparation. The thigh involved, time-point of collection, size of fiber bundles, and time that elapsed after biopsy had minor or no effect.
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17.
  • Cardinale, Daniele A., et al. (författare)
  • Resistance Training with Co-ingestion of Anti-inflammatory Drugs Attenuates Mitochondrial Function
  • 2017
  • Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: The current study aimed to examine the effects of resistance exercise with concomitant consumption of high versus low daily doses of non-steroidal anti-inflammatory drugs (NSAIDs) on mitochondrial oxidative phosphorylation in skeletal muscle. As a secondary aim, we compared the effects of eccentric-overload with conventional training. Methods: Twenty participants were randomized to either a group taking high doses (3 x 400 mg/day) of ibuprofen (IBU; 27±5 yr; n=11) or a group ingesting a low dose (1 x 75 mg/day) of acetylsalicylic acid (ASA; 26±4 yr; n=9) during 8 weeks of supervised knee extensor resistance training. Each of the subject’s legs were randomized to complete the training program using either a flywheel (FW) device emphasizing eccentric-overload, or a traditional weight stack machine (WS). Maximal mitochondrial oxidative phosphorylation (CI+IIP) from permeabilized skeletal muscle bundles was assessed using high-resolution respirometry. Citrate synthase (CS) activity was assessed using spectrophotometric techniques and mitochondrial protein content using western blotting. Results: After training, CI+IIP decreased (P<0.05) in both IBU (23%) and ASA (29%) with no difference across medical treatments. Although CI+IIP decreased in both legs, the decrease was greater (interaction p = 0.015) in WS (33%, p = 0.001) compared with FW (19%, p = 0.078). CS activity increased (p = 0.027) with resistance training, with no interactions with medical treatment or training modality. Protein expression of ULK1 increased with training in both groups (p < 0.001). The increase in quadriceps muscle volume was not correlated with changes in CI+IIP (R=0.16). Conclusion: These results suggest that 8 weeks of resistance training with co-ingestion of anti-inflammatory drugs reduces mitochondrial function but increases mitochondrial content. The observed changes were not affected by higher doses of NSAIDs consumption, suggesting that the resistance training intervention was the prime mediator of the decreased mitochondrial phosphorylation. Finally, we noted that flywheel resistance training, emphasizing eccentric overload, rescued some of the reduction in mitochondrial function seen with conventional resistance training.
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18.
  • Cardinale, Daniele A., 1982-, et al. (författare)
  • Short term intensified training temporarily impairs mitochondrial respiratory capacity in elite endurance athletes.
  • 2021
  • Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 131:1, s. 388-400
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: The maintenance of healthy and functional mitochondria is the result of a complex mitochondrial turnover and herein quality-control program which includes both mitochondrial biogenesis and autophagy of mitochondria. The aim of this study was to examine the effect of an intensified training load on skeletal muscle mitochondrial quality control in relation to changes in mitochondrial oxidative capacity, maximal oxygen consumption and performance in highly trained endurance athletes.METHODS: 27 elite endurance athletes performed high intensity interval exercise followed by moderate intensity continuous exercise 3 days per week for 4 weeks in addition to their usual volume of training. Mitochondrial oxidative capacity, abundance of mitochondrial proteins, markers of autophagy and antioxidant capacity of skeletal muscle were assessed in skeletal muscle biopsies before and after the intensified training period.RESULTS: The intensified training period increased several autophagy markers suggesting an increased turnover of mitochondrial and cytosolic proteins. In permeabilized muscle fibers, mitochondrial respiration was ~20 % lower after training although some markers of mitochondrial density increased by 5-50%, indicative of a reduced mitochondrial quality by the intensified training intervention. The antioxidative proteins UCP3, ANT1, and SOD2 were increased after training, whereas we found an inactivation of aconitase. In agreement with the lower aconitase activity, the amount of mitochondrial LON protease that selectively degrades oxidized aconitase, was doubled.CONCLUSION: Together, this suggests that mitochondrial respiratory function is impaired during the initial recovery from a period of intensified endurance training while mitochondrial quality control is slightly activated in highly trained skeletal muscle.
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19.
  • Cardinale, Daniele A., 1982-, et al. (författare)
  • Superior Intrinsic Mitochondrial Respiration in Women Than in Men.
  • 2018
  • Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9
  • 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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20.
  • Cardinale, Daniele A., 1982- (författare)
  • The significance of mitochondrial respiratory function in regulating oxygen uptake and performance in humans
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The mitochondrion is one of the most fascinating organelles of our cells which has kept and keeps researchers busy in studying its origin, the complex morphology, the numerous functions, the rapid adaptations to a variety of stimuli and its role in health and disease. Exercise challenges cellular homeostasis and skeletal muscle mitochondria greatly adapt to repeated bouts of exercise by increasing mitochondrial respiratory function and content to match energy requirements and to better sustain future perturbations induced by muscle contractions. The oxidative capacity of mitochondria has been shown to exceed the capacity of the cardiorespiratory system to supply oxygen to active muscle at maximal exercise intensity. Despite this, exercise training further increases this overcapacity. Little is known about the role of this excess oxidative capacity of mitochondria in regulating oxygen consumption, the role of oxygen delivery in determining exercise-induced skeletal muscle adaptations, and whether any sex-related differences exist. The assessment of mitochondrial respiratory function in high resolution respirometer is largely used for clinical and scientific purposes. However, the reliability of this method has not been systematically investigated and warrant further investigation.With this background, specific measures of reliability associated with repeated determination of maximal mitochondrial oxidative phosphorylation in saponin-permeabilized fibres, comparison of the right and left legs, variability with measurements at different time-points and over time, as well as influence of the local anesthetic and wet weight of the fiber bundle on determined maximal mitochondrial oxidative phosphorylation were investigated in paper I. The importance of having the same technicians in preparing the samples, and that the major source of variation in measuring mitochondrial oxidative capacity is the sample preparation per se were shown. Furthermore, other factors such as the possible difference between left and right limbs, two time points of sample collection, fibres bundle weight, time that elapsed after collection of the biopsy, and the use of an anesthetic have only a minor impact on the standard error of the measurement.In paper II the physiological significance of having a mitochondrial oxidative capacity in excess of the capacity of the central circulation to deliver oxygen to the tissue was shown by integrating measures of ex vivo mitochondrial respiratory function with direct in vivo measure of oxygen consumption when performing two-legged cycling and one-legged knee extension exercise while inspiring atmospheric air and oxygen enriched air in the same participants. Excess capacity of mitochondria allows submaximal mitochondrial activation at maximal oxygen delivery, thereby maintaining a high mitochondrial oxygen affinity and a high oxygen extraction peripherally. Considering the widespread and increasing sedentary behavior in a society plagued by diseases often linked to mitochondrial dysfunction, these results suggest the importance of preserving a high muscle oxidative capacity throughout life, which can be of significance in patients with heart, circulatory, and overall metabolic diseases.Despite known sex-specific metabolic differences in human skeletal muscle and that animal models have consistently shown females having a superior mitochondrial function compare to males, data in humans are lacking. In paper III the first evidence that women possess higher mitochondrial quality compared to men with equal cardiorespiratory fitness and endurance performance was provided. Mitochondrial oxygen affinity varied with the degree of mitochondrial respiration rate and was lower in women compared to men. These results indicate that the higher mitochondrial quality in women may be an important physiological adaptation that compensates for the lower mitochondrial oxygen affinity allowing a higher oxygen extraction peripherally. Moreover, these results could possibly be linked to the difference in life expectancy, disease occurrence and aging between women and men.Lastly, in paper IV it was shown that increasing oxygen delivery and exercise intensity by means of breathing hyperoxia during high-intensity exercise did not enhance cardiorespiratory fitness and exercise-induced skeletal muscle adaptations but still resulted in a small beneficial effect on performance in trained cyclists. This small positive effect on performance can be exploited in elite athletes; however, considering the cost/benefit, the unknown health-related problems, and ethical issues of performing hyperoxic-supplemented endurance training, it is arguable if the use of this strategy to maximize endurance performance is worthwhile.Overall, this thesis provides useful information for future research on various factors influencing the error of the measurement when assessing mitochondrial respiratory function. Moreover, this thesis sheds light on novel factors that regulate oxygen consumption during exercise, highlighting the importance of maintaining a good mitochondrial function. This thesis also provides possible directions for future studies on mitochondrial function, metabolism and exercise-induced adaptations.  
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21.
  • Cardinale, Daniele, et al. (författare)
  • Resistance Exercise Attenuates Mitochondrial Function : Effects Of NSAID Intake And Eccentric-Overload Training
  • 2017
  • Ingår i: Medicine &amp; Science in Sports &amp; Exercise. 49(5S):329, MAY 2017. - : Ovid Technologies (Wolters Kluwer Health). ; , s. 329-329
  • Konferensbidrag (refereegranskat)abstract
    • Although nonsteroidal antiinflammatorydrugs (NSAIDs) have been shown to modulate skeletal muscle adaptations and protein metabolism in response toresistance exercise, little is known about the effects of NSAIDs on mitochondrial function. Thus, the current study aimed to examine the effects of resistanceexercise with concomitant NSAID consumption on mitochondrial oxidative phosphorylation in skeletal muscle. Twenty participants were randomized in asingleblindedfashion to either an experimental group receiving ibuprofen (IBU: 27±5 yr; n=11; 1200 mg/d) or a control group receiving a lowdoseacetylsalicylic acid (CON: 26±4 yr; n=9; 75 mg/d) During this period, subjects performed 8 weeks of supervised resistance exercise involving the kneeextensors muscles. Each of the subject’s legs were randomized to complete the training program using either a flywheel (FW) device emphasizing eccentricoverload,or a traditional weight stack machine (WS). Maximal mitochondrial oxidative phosphorylation (OXPHOS) from permeabilized skeletal muscle bundleswas assessed using high resolution respirometry before and after the training intervention. Citrate synthase activity was assessed using spectrophotometrictechniques. After training, OXPHOS decreased (P<0.05) in both IBU (23%) and CON (29%) with no difference across medical treatments. Although OXPHOSdecreased in both legs, the decrease was greater (interaction P= 0.015) in WS (33%, P= 0.015) than in FW (19%, P= 0.078). Citrate synthase (CS) did notchange after the intervention. The increase in quadriceps muscle volume was not significantly correlated with the change in OXPHOS (R=0.15). These resultssuggest that 1) eight weeks of resistance training reduces mitochondrial function but not mitochondrial content, 2) The decreased mitochondrial function withresistance exercise was not affected by ibuprofen consumption, 3) flywheel resistance training, emphasizing eccentric overload, rescues some of thereduction in mitochondrial function seen with conventional resistance training.
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22.
  • Carlström, Mattias, et al. (författare)
  • Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice
  • 2010
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:41, s. 17716-17720
  • Tidskriftsartikel (refereegranskat)abstract
    • The metabolic syndrome is a clustering of risk factors of metabolic origin that increase the risk for cardiovascular disease and type 2 diabetes. A proposed central event in metabolic syndrome is a decrease in the amount of bioavailable nitric oxide (NO) from endothelial NO synthase (eNOS). Recently, an alternative pathway for NO formation in mammals was described where inorganic nitrate, a supposedly inert NO oxidation product and unwanted dietary constituent, is serially reduced to nitrite and then NO and other bioactive nitrogen oxides. Here we show that several features of metabolic syndrome that develop in eNOS-deficient mice can be reversed by dietary supplementation with sodium nitrate, in amounts similar to those derived from eNOS under normal conditions. In humans, this dose corresponds to a rich intake of vegetables, the dominant dietary nitrate source. Nitrate administration increased tissue and plasma levels of bioactive nitrogen oxides. Moreover, chronic nitrate treatment reduced visceral fat accumulation and circulating levels of triglycerides and reversed the prediabetic phenotype in these animals. In rats, chronic nitrate treatment reduced blood pressure and this effect was also present during NOS inhibition. Our results show that dietary nitrate fuels a nitrate-nitrite-NO pathway that can partly compensate for disturbances in endogenous NO generation from eNOS. These findings may have implications for novel nutrition-based preventive and therapeutic strategies against cardiovascular disease and type 2 diabetes.
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23.
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24.
  • Edman, Sebastian, et al. (författare)
  • Need for speed : Human fast-twitch mitochondria favor power over efficiency
  • 2024
  • Ingår i: Molecular Metabolism. - : Elsevier. - 2212-8778. ; 79
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Human skeletal muscle consists of a mixture of slow- and fast-twitch fibers with distinct capacities for contraction mechanics, fermentation, and oxidative phosphorylation. While the divergence in mitochondrial volume favoring slow-twitch fibers is well established, data on the fiber type-specific intrinsic mitochondrial function and morphology are highly limited with existing data mainly being generated in animal models. This highlights the need for more human data on the topic.Methods: Here, we utilized THRIFTY, a rapid fiber type identification protocol to detect, sort, and pool fast- and slow-twitch fibers within 6 h of muscle biopsy sampling. Respiration of permeabilized fast- and slow-twitch fiber pools was then analyzed with high-resolution respirometry. Using standardized western blot procedures, muscle fiber pools were subsequently analyzed for control proteins and key proteins related to respiratory capacity.Results: Maximal complex I+II respiration was 25% higher in human slow-twitch fibers compared to fast-twitch fibers. However, per mitochondrial volume, the respiratory rate of mitochondria in fast-twitch fibers was approximately 50% higher for complex I+II, which was primarily mediated through elevated complex II respiration. Furthermore, the abundance of complex II protein and proteins regulating cristae structure were disproportionally elevated in mitochondria of the fast-twitch fibers. The difference in intrinsic respiratory rate was not reflected in fatty acid–or complex I respiration.Conclusion: Mitochondria of human fast-twitch muscle fibers compensate for their lack of volume by substantially elevating intrinsic respiratory rate through increased reliance on complex II.
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25.
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26.
  • Edman, Sebastian, 1990- (författare)
  • Skeletal muscle fiber types in man : With special reference to anabolic signaling and mitochondrial bioenergetics
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Human skeletal muscle consists of a mixture of slow-twitch (type I) and fast-twitch (type II) fibers. The type I fibers are endurance-oriented, with a metabolic system and infrastructure that supports aerobic metabolism. This entails a well-developed capillary grid and a mitochondrial network proportioned to the number of contractile units within the fiber. These fibers generally have slower and less forceful contraction mechanics and more limited muscle growth as a resource-efficient metabolic energy system is prioritized over increasing the number of contractile units. By contrast, type II fibers prioritize contractile capabilities and force generation at the cost of resource efficiency. These fibers have a substantially lower mitochondrial volume but prioritize structures and organelles that benefit muscle contraction instead. It is well known that resistance exercise combined with dietary protein intake stimulates the growth of contractile proteins leading to an increased muscle mass over time. Muscle mass accumulation is primarily driven by the amplification of muscle protein synthesis, which in turn is largely governed by the mTORC1 signaling pathway within the muscle cell. Little is known about how mTORC1 signaling regulates growth in the different fiber types. Furthermore, it is unknown whether blunted anabolic signaling in type II fibers of the elderly may explain why losses of muscle mass occur primarily in these fibers with advancing age.Endurance exercise, on the other hand, primarily stimulates a prioritization to synthesize new mitochondria to support the high demand for sustainable aerobic energy output. However, it remains to be determined if mitochondria created within type I and type II fibers are equal, or whether they have adapted to their respective milieu in any way. Therefore, the aim of the current thesis was to investigate how the mTORC1 pathway in type I and type II fibers responds to resistance exercise and nutritional stimuli in the form of essential amino acids (EAA), and to determine if this response is influenced by age. Fiber type-specific mitochondrial populations, including their respiratory capacity, were also investigated. To facilitate these investigations, a new and improved method for muscle fiber type identification was developed.In paper I, the phosphorylation of mTORC1 in response to resistance exercise and EAA intake was examined in 684 individual muscle fibers. Unsurprisingly, a significant increase in mTORC1 signaling was seen following the combination of resistance exercise and EAA intake, whereas the rise following resistance exercise alone was more modest. However, no evidence of a discrete response in the different fiber types was found. In paper II, a new method was developed to facilitate the work surrounding fiber type-specific muscle physiology by limiting the extreme time requirements of fiber type identification of large sample sets of muscle fibers. The novel method, which was named THRIFTY, allows an experienced technician to classify over 800 fibers in under 11h.Paper III utilizes the high throughput of the THRIFTY method described in paper II to create the most extensive study to date on individually dissected muscle fibers with 27 602 included fibers. Here, the aim was to investigate whether the fiber type-specific muscle atrophy of the type II fibers in aging could be explained by an onset of anabolic resistance in these fibers. For this investigation, ten young and ten elderly men were recruited to perform a unilateral resistance exercise session followed by ingestion of EAA. This paper showed a slightly elevated mTORC1 signaling response in type I fibers. However, there were no signs of blunted mTORC1 signaling in the elderly. In paper IV, the high speed of the THRIFTY method was utilized to analyze the mitochondrial respiratory function of permeabilized type I and type II muscle fibers. In addition, the intrinsic protein expression of mitochondria in the type I and type II muscle fibers was analyzed. As expected, a higher volume of mitochondria and a greater respiratory rate in the type I fibers were found. However, on a per mitochondria basis, a higher maximal respiratory rate was observed in type II fibers together with increased levels of proteins in the electron transport chain. Likewise, proteins regulating mitochondrial fission and fusion were more highly expressed in the type II fiber mitochondria, which may be a compensatory mechanism for the low volume. In conclusion, both fiber types show robust increases in mTORC1 signaling in response to exercise and EAA ingestion. The results indicate that the response is slightly stronger in the type I fibers, which is contrary to what was predicted. Moreover, the highly specific type II fiber atrophy seen with aging cannot be explained by a blunted anabolic response in these fibers. Surprisingly, the mitochondria of type II fibers possess a higher respiratory capacity. However, this discrepancy is concealed by the vast difference in mitochondrial volume favoring type I fibers, ultimately leading to an overall greater respiratory rate in the type I fibers.
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27.
  • Flockhart, Mikael, et al. (författare)
  • A simple model for diagnosis of maladaptations to exercise training
  • 2022
  • Ingår i: Sports Medicine Open. - : Springer. - 2198-9761 .- 2199-1170. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The concept of overreaching and super compensation is widely in use by athletes and coaches seeking to maximize performance and adaptations to exercise training. The physiological aspects of acute fatigue, overreaching and non-functional overreaching are, however, not well understood, and well-defined negative physiological outcomes are missing. Instead, the concept relies heavily on performance outcomes for differentiating between the states. Recent advancements in the field of integrated exercise physiology have associated maladaptations in muscular oxidative function to high loads of exercise training.Method: Eleven female and male subjects that exercised regularly but did not engage in high-intensity interval training (HIIT) were recruited to a 4-week long training intervention where the responses to different training loads were studied. Highly monitored HIIT sessions were performed on a cycle ergometer in a progressive fashion with the intent to accomplish a training overload. Throughout the intervention, physiological and psychological responses to HIIT were assessed, and the results were used to construct a diagnostic model that could indicate maladaptations during excessive training loads.Results: We here use mitochondrial function as an early marker of excessive training loads and show the dynamic responses of several physiological and psychological measurements during different training loads. During HIIT, a loss of mitochondrial function was associated with reduced glycolytic, glucoregulatory and heart rate responses and increased ratings of perceived exertion in relation to several physiological measurements. The profile of mood states was highly affected after excessive training loads, whereas performance staled rather than decreased. By implementing five of the most affected and relevant measured parameters in a diagnostic model, we could successfully, and in all the subjects, identify the training loads that lead to maladaptations.Conclusions: As mitochondrial parameters cannot be assessed without donating a muscle biopsy, this test can be used by coaches and exercise physiologists to monitor adaptation to exercise training for improving performance and optimizing the health benefits of exercise. Clinical trial registry number NCT04753021 . Retrospectively registered 2021-02-12.
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28.
  • Flockhart, Mikael, et al. (författare)
  • Continuous Glucose Monitoring in Endurance Athletes : Interpretation and Relevance of Measurements for Improving Performance and Health.
  • 2024
  • Ingår i: Sports Medicine. - : Springer. - 0112-1642 .- 1179-2035. ; 54:2, s. 247-255
  • Tidskriftsartikel (refereegranskat)abstract
    • Blood glucose regulation has been studied for well over a century as it is intimately related to metabolic health. Research in glucose transport and uptake has also been substantial within the field of exercise physiology as glucose delivery to the working muscles affects exercise capacity and athletic achievements. However, although exceptions exist, less focus has been on blood glucose as a parameter to optimize training and competition outcomes in athletes with normal glucose control. During the last years, measuring glucose has gained popularity within the sports community and successful endurance athletes have been seen with skin-mounted sensors for continuous glucose monitoring (CGM). The technique offers real-time recording of glucose concentrations in the interstitium, which is assumed to be equivalent to concentrations in the blood. Although continuous measurements of a parameter that is intimately connected to metabolism and health can seem appealing, there is no current consensus on how to interpret measurements within this context. Well-defined approaches to use glucose monitoring to improve endurance athletes' performance and health are lacking. In several studies, blood glucose regulation in endurance athletes has been shown to differ from that in healthy controls. Furthermore, endurance athletes regularly perform demanding training sessions and can be exposed to high or low energy and/or carbohydrate availability, which can affect blood glucose levels and regulation. In this current opinion, we aim to discuss blood glucose regulation in endurance athletes and highlight the existing research on glucose monitoring for performance and health in this population.
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29.
  • Flockhart, Mikael, et al. (författare)
  • Dose-response relationship between exercise load and mitochondrial function
  • 2019
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Dose-response relationship between exercise load and mitochondrial functionFlockhart M, Nilsson L, Bergman K, Apro W, Ekblom B, Larsen FJA dose-dependent relationship exists between exercise load and muscular adaptation. Mitochondria adapt to the increased ATP-demand by alterations in mass and/or quality. How mitochondrial mass and quality changes as a function of exercise load is not well investigated and we have previously found mitochondrial dysfunction after short-term intensive exercise. We therefore aimed to study mitochondrial function by altering exercise load during a three week interval training regimen to understand the dose-response relationship between exercise load and mitochondrial function. We took four muscle biopsies throughout the study, and as expected, mitochondrial function was positively affected during the first two weeks. After the third week, a dramatic mitochondrial dysfunction was evident as mitochondrial intrinsic respiration was reduced by 26% despite a 32% increase in mitochondrial yield. We hereby present evidence of a striking exercise-induced reduction in mitochondrial function after a period of very intense interval training.
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30.
  • Flockhart, Mikael, et al. (författare)
  • Excessive exercise training causes mitochondrial functional impairment and decreases glucose tolerance in healthy volunteers.
  • 2021
  • Ingår i: Cell Metabolism. - : Cell Press. - 1550-4131 .- 1932-7420. ; 33:5, s. 957-970
  • Tidskriftsartikel (refereegranskat)abstract
    • Exercise training positively affects metabolic health through increased mitochondrial oxidative capacity and improved glucose regulation and is the first line of treatment in several metabolic diseases. However, the upper limit of the amount of exercise associated with beneficial therapeutic effects has not been clearly identified. Here, we used a training model with a progressively increasing exercise load during an intervention over 4 weeks. We closely followed changes in glucose tolerance, mitochondrial function and dynamics, physical exercise capacity, and whole-body metabolism. Following the week with the highest exercise load, we found a striking reduction in intrinsic mitochondrial function that coincided with a disturbance in glucose tolerance and insulin secretion. We also assessed continuous blood glucose profiles in world-class endurance athletes and found that they had impaired glucose control compared with a matched control group.
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31.
  • Flockhart, Mikael, 1980- (författare)
  • Exercising on the edge: mitochondrial and metabolic responses to intense training
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Exercise and exercise training induces several physiological adaptations that increase the oxidative capacity of the muscles and improve glucose regulation. While the positive metabolic adaptations and effects on glucose regulation after exercise and exercise training have been extensively studied, negative outcomes have not. This thesis aims to address these questions and investigate possible negative effects of intensified training on mitochondrial parameters and glucose regulation.In two separate interventions, we studied these outcomes after progressive exercise training, and after different intensities of exercise. Mitochondrial respiration was assessed in muscle biopsies taken from m. vastus lateralis 14 hours after exercise and oral glucose tolerance tests were performed at the same time point.In paper I, we demonstrate that there is an upper limit of training load that can be tolerated without the manifestation of negative outcomes. After administrating almost daily sessions of high-intensity interval training, mitochondrial function and glucose control were impaired. In paper II, we used mitochondrial function as a novel biomarker of maladaptive training loads and constructed a diagnostic model that can be used for the early detection of maladaptations to exercise training. In paper III, we further demonstrated that endurance-trained athletes can have decreased glucose tolerance and increased insulin resistance the day after three hours of continuous cycling whereas these responses were not accentuated in healthy controls. Our results indicate that a metabolic switch in favor of lipid metabolism is the probable cause of this phenomenon. In paper IV, we briefly commented on a publication that described changes in whole-body VO2 responses to work rates in the athlete with the highest recorded VO2max. We provided arguments that the observed changes in VO2 and gross efficiency can in part have their origin in the mitochondria.We here combine measurements in muscle tissue with physiological measurements in an applied context. Using this integrated approach, we investigated the effects of intensified training on health-related and performance outcomes, thereby presenting insights into what maladaptations to exercise can constitute. We hope that our results and conclusions can help to further understand the complex relationship between exercise and health and to guide athletes and coaches to optimize training outcomes.
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32.
  • Flockhart, Mikael, et al. (författare)
  • Glucosinolate-rich broccoli sprouts protect against oxidative stress and improve adaptations to intense exercise training.
  • 2023
  • Ingår i: Redox Biology. - : Elsevier. - 2213-2317. ; 67
  • Tidskriftsartikel (refereegranskat)abstract
    • Oxidative stress plays a vital role for the adaptive responses to physical training. However, excessive oxidative stress can precipitate cellular damage, necessitating protective mechanisms to mitigate this effect. Glucosinolates, found predominantly in cruciferous vegetables, can be converted into isothiocyanates, known for their antioxidative properties. These compounds activate crucial antioxidant defence pathways and support mitochondrial function and protein integrity under oxidative stress, in both Nrf2-dependent and independent manners. We here administered glucosinolate-rich broccoli sprouts (GRS), in a randomized double-blinded cross-over fashion to 9 healthy subjects in combination with daily intense exercise training for 7 days. We found that exercise in combination with GRS significantly decreased the levels of carbonylated proteins in skeletal muscle and the release of myeloperoxidase into blood. Moreover, it lowered lactate accumulation during submaximal exercise, and attenuated the severe nocturnal hypoglycaemic episodes seen during the placebo condition. Furthermore, GRS in combination with exercise improved physical performance, which was unchanged in the placebo condition.
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33.
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34.
  • Gejl, Kasper Degn, et al. (författare)
  • No Superior Adaptations to Carbohydrate Periodization in Elite Endurance Athletes
  • 2017
  • Ingår i: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 49:12, s. 2486-2497
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose The present study investigated the effects of periodic carbohydrate (CHO) restriction on endurance performance and metabolic markers in elite endurance athletes. Methods Twenty-six male elite endurance athletes (maximal oxygen consumption (VO2max), 65.0 mL O(2)kg(-1)min(-1)) completed 4 wk of regular endurance training while being matched and randomized into two groups training with (low) or without (high) CHO manipulation 3 dwk(-1). The CHO manipulation days consisted of a 1-h high-intensity bike session in the morning, recovery for 7 h while consuming isocaloric diets containing either high CHO (414 2.4 g) or low CHO (79.5 1.0 g), and a 2-h moderate bike session in the afternoon with or without CHO. VO2max, maximal fat oxidation, and power output during a 30-min time trial (TT) were determined before and after the training period. The TT was undertaken after 90 min of intermittent exercise with CHO provision before the training period and both CHO and placebo after the training period. Muscle biopsies were analyzed for glycogen, citrate synthase (CS) and -hydroxyacyl-coenzyme A dehydrogenase (HAD) activity, carnitine palmitoyltransferase (CPT1b), and phosphorylated acetyl-CoA carboxylase (pACC). Results The training effects were similar in both groups for all parameters. On average, VO2max and power output during the 30-min TT increased by 5% +/- 1% (P < 0.05) and TT performance was similar after CHO and placebo during the preload phase. Training promoted overall increases in glycogen content (18% +/- 5%), CS activity (11% +/- 5%), and pACC (38% +/- 19%; P < 0.05) with no differences between groups. HAD activity and CPT1b protein content remained unchanged. Conclusions Superimposing periodic CHO restriction to 4 wk of regular endurance training had no superior effects on performance and muscle adaptations in elite endurance athletes.
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35.
  • Horwath, Oscar, 1991-, et al. (författare)
  • Influence of sex- and fiber type on the satellite cell pool in human skeletal muscle.
  • 2021
  • Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 31:2, s. 303-312
  • Tidskriftsartikel (refereegranskat)abstract
    • The repair, remodeling and regeneration of myofibers is dependent on satellite cells (SCs), although, the distribution of SCs in different fiber types of human muscle remains inconclusive. There is also a paucity of research comparing muscle fiber characteristics in a sex-specific manner. Therefore, the aim of this study was to investigate fiber type-specific SC content in men and women. Muscle biopsies from vastus lateralis were collected from 64 young (mean age 27 ± 5), moderately trained men (n=34) and women (n=30). SCs were identified by Pax7-staining together with immunofluorescent analyses of fiber type composition, fiber size and myonuclei content. In a mixed population, comparable number of SCs were associated to type I and type II fibers (0.07 ± 0.02 vs 0.07 ± 0.02 SCs per fiber, respectively). However, unlike men, women displayed a fiber type-specific distribution, with SC content being lower in type II than type I fibers (P=0.041). Sex-based differences were found specifically for type II fibers, where women displayed lower SC content compared to men (P<0.001). In addition, positive correlations (r-values between 0.36-0.56) were found between SC content and type I and type II fiber size in men (P=0.03 and P<0.01, respectively), whereas similar relationships could not be detected in women. Sex-based differences were also noted for fiber type composition and fiber size, but not for myonuclei content. We hereby provide evidence for sex-based differences present at the myocellular level, which may have important implications when studying exercise- and training induced myogenic responses in skeletal muscle.
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36.
  • Horwath, Oscar, 1991-, et al. (författare)
  • THRIFTY : a novel high-throughput method for rapid fibre type identification of isolated skeletal muscle fibres.
  • 2022
  • Ingår i: Journal of Physiology. - : The physiological society. - 0022-3751 .- 1469-7793. ; 600:20, s. 4421-4438
  • Tidskriftsartikel (refereegranskat)abstract
    • Fibre type-specific analyses are required for broader understanding of muscle physiology, but such analyses are difficult to conduct due to the extreme time requirements of dissecting and fibre typing individual fibres. Investigations are often confined to a small number of fibres from few participants with low representativeness of the entire fibre population and the participant population. To increase the feasibility of conducting large-scale fibre type-specific studies, a valid and rapid method for high-throughput fibre typing of individually dissected fibres was developed and named THRIFTY (for high-THRoughput Immunofluorescence Fibre TYping). Employing THRIFTY, 400 fibre segments were fixed onto microscope slides with a pre-printed coordinated grid system, probed with antibodies against myosin heavy chain (MyHC)-I and MyHC-II and classified using a fluorescence microscope. The validity and speed of THRIFTY was compared to a previously validated protocol (dot blot) on a fibre-to-fibre basis. Fibre pool purity was evaluated using 'gold standard' SDS-PAGE and silver staining. A modified THRIFTY-protocol using fluorescence western blot equipment was also validated. THRIFTY displayed excellent agreement with the dot blot protocol, κ = 0.955 (95% CI: 0.928, 0.982), P < 0.001. Both the original and modified THRIFTY protocols generated type I and type II fibre pools of absolute purity. Using THRIFTY, 400 fibres were typed just under 11 h, which was approximately 3 times faster than dot blot. THRIFTY is a novel and valid method with high versatility for very rapid fibre typing of individual fibres. THRIFTY can therefore facilitate the generation of large fibre pools for more extensive mechanistic studies into skeletal muscle physiology. KEY POINTS: Skeletal muscle is composed of different fibre types, each with distinct physiological properties. To fully understand how skeletal muscle adapts to external cues such as exercise, nutrition and ageing, fibre type-specific investigations are required. Such investigations are very difficult to conduct due to the extreme time requirements related to classifying individually isolated muscle fibres. To bypass this issue, we have developed a rapid and reliable method named THRIFTY which is cheap as well as versatile and which can easily be implemented in most laboratories. THRIFTY increases the feasibility of conducting larger fibre type-specific studies and enables time-sensitive assays where measurements need to be carried out in close connection with tissue sampling. By using THRIFTY, new insights into fibre type-specific muscle physiology can be gained which may have broad implications in health and disease.
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37.
  • Larsen, Filip J, et al. (författare)
  • Cardiorespiratory fitness predicts insulin action and secretion in healthy individuals.
  • 2012
  • Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 61:1, s. 12-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Long-term cardiorespiratory fitness (CRF) and the development of type 2 diabetes mellitus are inversely correlated. Here, we examined the relationships between peak oxygen uptake (VO(2)peak), on the one hand, and glucose infusion rate at rest (GIR(rest)) and during exercise (GIR(exercise)), as well as insulin secretion (both the early and late phases of response [area under the curve {AUC}(insulin)]), on the other. Eight male and 4 female healthy, lean, nonsmoking volunteers were recruited. The VO(2)peak was measured during graded exercise on a cycle ergometer until exhaustion was reached. The GIR(rest) and GIR(exercise) were determined using a euglycemic-hyperinsulinemic clamp, and insulin secretion at rest was evaluated with an intravenous glucose tolerance test. The VO(2)peak correlated positively to GIR(rest) (r = 0.81, P = .001) and GIR(exercise) (r = 0.87, P < .001) and negatively to AUC(insulin) (r = -0.64, P = .03). The respiratory exchange ratio (RER) during insulin infusion was positively correlated to GIR(rest) (r = 0.83, P < .001) and GIR(exercise) (r = 0.86, P < .01) and negatively correlated to both the early insulin response (r = -0.86, P < .0001) and AUC(insulin) (r = -0.87, P = .001). The VO(2)peak accounted for 45% of the variability in RER (R(2) = 0.45, P = .035). In this healthy population, CRF and RER were highly correlated to insulin sensitivity and secretion, as well as to the ability to alter the substrate being oxidized during exercise. These findings highlight the importance of good CRF to maintaining normal insulin action.
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38.
  • Larsen, Filip J. (författare)
  • Dietary inorganic nitrate : role in exercise physiology, cardiovascular and metabolic regulation
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Nitric oxide (NO) is a ubiquitous signaling molecule with a vast number of tasks in the body, including regulation of cardiovascular and metabolic function. A decreased bioavailability of NO is a central event in disorders such as hypertension and metabolic syndrome. NO is also important in the regulation of blood flow and metabolism during exercise. The production of NO has previously been thought to be under the exclusive control of the nitric oxide synthases (NOS) but this view is now being seriously challenged. Recent lines of research suggest the existence of an NO-synthase independent pathway in which the supposedly inert NO oxidation products nitrate (NO3-) and nitrite (NO2-) can be reduced back to NO in blood and tissues. An important additional source of nitrate is our everyday diet and certain vegetables are particularly rich in this anion. In this thesis the possibility that dietary derived nitrate is metabolized in vivo to form reactive nitrogen oxides with NO-like bioactivity has been explored. It is shown that nitrate in amounts easily achieved via the diet, increases the systemic levels of nitrite and reduces blood pressure in healthy humans. Moreover, nitrate reduces whole body oxygen cost during submaximal and maximal exercise; a surprising effect involving improvement in mitochondrial efficiency and reduced expression of specific mitochondrial proteins regulating proton conductance. Alterations in the mitochondrial affinity for oxygen can explain this reduction in both submaximal and maximal oxygen consumption and predicts basal metabolic rate in humans. Finally, in mice lacking endothelial NO synthase, dietary supplementation with nitrate could reverse several features of the metabolic syndrome that develop in these animals. These studies demonstrate that dietary nitrate can fuel a nitrate-nitrite-NO pathway with important implications for cardiovascular and metabolic functions in health and disease.
  •  
39.
  • Larsen, Filip J, et al. (författare)
  • Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise.
  • 2010
  • Ingår i: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 48:2, s. 342-7
  • Tidskriftsartikel (refereegranskat)abstract
    • The anion nitrate-abundant in our diet-has recently emerged as a major pool of nitric oxide (NO) synthase-independent NO production. Nitrate is reduced stepwise in vivo to nitrite and then NO and possibly other bioactive nitrogen oxides. This reductive pathway is enhanced during low oxygen tension and acidosis. A recent study shows a reduction in oxygen consumption during submaximal exercise attributable to dietary nitrate. We went on to study the effects of dietary nitrate on various physiological and biochemical parameters during maximal exercise. Nine healthy, nonsmoking volunteers (age 30+/-2.3 years, VO(2max) 3.72+/-0.33 L/min) participated in this study, which had a randomized, double-blind crossover design. Subjects received dietary supplementation with sodium nitrate (0.1 mmol/kg/day) or placebo (NaCl) for 2 days before the test. This dose corresponds to the amount found in 100-300 g of a nitrate-rich vegetable such as spinach or beetroot. The maximal exercise tests consisted of an incremental exercise to exhaustion with combined arm and leg cranking on two separate ergometers. Dietary nitrate reduced VO(2max) from 3.72+/-0.33 to 3.62+/-0.31 L/min, P<0.05. Despite the reduction in VO(2max) the time to exhaustion trended to an increase after nitrate supplementation (524+/-31 vs 563+/-30 s, P=0.13). There was a correlation between the change in time to exhaustion and the change in VO(2max) (R(2)=0.47, P=0.04). A moderate dietary dose of nitrate significantly reduces VO(2max) during maximal exercise using a large active muscle mass. This reduction occurred with a trend toward increased time to exhaustion implying that two separate mechanisms are involved: one that reduces VO(2max) and another that improves the energetic function of the working muscles.
  •  
40.
  • Larsen, Filip J, et al. (författare)
  • Dietary nitrate reduces resting metabolic rate : a randomized, crossover study in humans.
  • 2014
  • Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 99:4, s. 843-50
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Nitrate, which is an inorganic anion abundant in vegetables, increases the efficiency of isolated human mitochondria. Such an effect might be reflected in changes in the resting metabolic rate (RMR) and formation of reactive oxygen species. The bioactivation of nitrate involves its active accumulation in saliva followed by a sequential reduction to nitrite, nitric oxide, and other reactive nitrogen species.OBJECTIVE: We studied effects of inorganic nitrate, in amounts that represented a diet rich in vegetables, on the RMR in healthy volunteers.DESIGN: In a randomized, double-blind, crossover study, we measured the RMR by using indirect calorimetry in 13 healthy volunteers after a 3-d dietary intervention with sodium nitrate (NaNO3) or a placebo (NaCl). The nitrate dose (0.1 mmol · kg(-1) · d(-1)) corresponded to the amount in 200-300 g spinach, beetroot, lettuce, or other vegetable that was rich in nitrate. Effects of direct nitrite exposure on cell respiration were studied in cultured human primary myotubes.RESULTS: The RMR was 4.2% lower after nitrate compared with placebo administration, and the change correlated strongly to the degree of nitrate accumulation in saliva (r(2) = 0.71). The thyroid hormone status, insulin sensitivity, glucose uptake, plasma concentration of isoprostanes, and total antioxidant capacity were unaffected by nitrate. The administration of nitrite to human primary myotubes acutely inhibited respiration.CONCLUSIONS: Dietary inorganic nitrate reduces the RMR. This effect may have implications for the regulation of metabolic function in health and disease.
  •  
41.
  • Lundberg, Jon O., et al. (författare)
  • Roles of dietary inorganic nitrate in cardiovascular health and disease
  • 2011
  • Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 89:3, s. 525-532
  • Forskningsöversikt (refereegranskat)abstract
    • Inorganic nitrate from dietary and endogenous sources is emerging as a substrate for in vivo generation of nitric oxide (NO) and other reactive nitrogen oxides. Dietary amounts of nitrate clearly have robust NO-like effects in humans, including blood pressure reduction, inhibition of platelet aggregation, and vasoprotective activity. In animal models, nitrate protects against ischaemia-reperfusion injuries and several other types of cardiovascular disorders. In addition, nitrate most surprisingly decreases whole body oxygen cost during exercise with preserved or even enhanced maximal performance. Oxidative stress and reduced NO bioavailability are critically linked to development of hypertension and other forms of cardiovascular diseases. Mechanistically, a central target for the effects of nitrate and its reaction products seems to be the mitochondrion and modulation of oxidative stress. All in vivo effects of nitrate are achievable with amounts corresponding to a rich intake of vegetables, which are particularly rich in this anion. A theory is now emerging suggesting nitrate as an active component in vegetables contributing to the beneficial health effects of this food group, including protection against cardiovascular disease and type-2 diabetes.
  •  
42.
  • Lundberg, Jon O, et al. (författare)
  • The Tortoise and the Hare.
  • 2023
  • Ingår i: Trends in endocrinology and metabolism. - : Elsevier. - 1043-2760 .- 1879-3061. ; 34:6, s. 317-318
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Distance running requires a high absolute oxygen consumption, while for a breath-hold diver the opposite is preferable. We compared physiological exercise parameters and mitochondrial function in a competitive triathlete with those seen in an accomplished breath-hold diver and notice some remarkable differences, possibly explaining why both have become successful.
  •  
43.
  • Lännerström, Johan, et al. (författare)
  • Effects of Plyometric Training on Soft and Hard Surfaces for Improving Running Economy.
  • 2021
  • Ingår i: Journal of Human Kinetics. - : Sciendo. - 1640-5544 .- 1899-7562. ; 79:1, s. 187-196
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study investigated the effects of plyometric jump training on hard and soft surfaces on running economy (RE), maximal oxygen uptake (VO2max), running performance and the rate of force development in orienteers. Nineteen orienteers (11 women and 8 men, body mass 61.1 ± 7.3 kg, age 21 ± 5.8 yrs) were randomly stratified based on sex, age, VO2max and RE to plyometric jumping training (8 sessions over 4 weeks) on either a hard or a soft surface. RE, VO2max and running performance were assessed on a treadmill and outdoor on- and off-trail loops. Moreover, ground reaction forces and force development were assessed during a one leg drop-jump test. The training intervention led to an overall 2-7% improvement in treadmill and off-trail RE, independent of the jumping surface and running velocity assessed. These improvements were not explained by force development during drop jump tests, which remained unchanged following the intervention. The changes in time-trial performance were associated with changes in RE. Plyometric training improved RE with no difference between the hard or the soft training surface and improved RE was also independent of the running speed assessed. Furthermore, improved running performance was associated with changes in RE after the intervention.
  •  
44.
  • Manselin, Tom A, et al. (författare)
  • Aerobic efficiency is associated with the improvement in maximal power output during acute hyperoxia.
  • 2017
  • Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 5:2
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigated the relationship between aerobic efficiency during cycling exercise and the increase in physical performance with acute hyperoxic exposure (FiO2 ~31%) (HOX) and also tested the hypothesis that fat oxidation could be increased by acute hyperoxia. Fourteen males and four females were recruited for two sessions, where they exercised for 2 × 10 min at 100 W to determine efficiency. HOX and normoxia (NOX) were administered randomly on both occasions to account for differences in nitrogen exchange. Thereafter, a progressive ramp test was performed to determine VO2max and maximal power output (Wmax). After 30 min rest, workload was set to 80% of maximal power output (Wmax) for a time to exhaustion test (TTE). At 100W gross efficiency was reduced from 19.4% during NOX to 18.9% during HOX (P ≤ 0.0001). HOX increased fat oxidation at 100 W by 52% from 3.41 kcal min(-1) to 5.17 kcal min(-1) (P ≤ 0.0001) with a corresponding reduction in carbohydrate oxidation. Wmax increased by 2.4% from 388.8 (±82.1) during NOX to 397.8 (±83.5) during HOX (P ≤ 0.0001). SaO2 was higher in HOX both at the end of the maximal exercise test and TTE. Subjects with a high level of efficiency in NOX had a larger improvement in Wmax with HOX, in agreement with the hypothesis that an optimum level of efficiency exists that maximizes power production. No association between mitochondrial excess capacity and endurance performance was found; increases in oxygen supply seemed to increase maximal aerobic power production and maintain/increase endurance capacity at the same relative workload.
  •  
45.
  • Mattsson, Mikael, 1979-, et al. (författare)
  • Individen i idrotten
  • 2019
  • Ingår i: Idrott och Kunskap. - Stockholm. - 1652-6961. ; 5:5, s. 14-21
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Sedan urminnes tider har det varit känt att olika träningsupplägg fungerar bättre för vissa idrottare än för andra. Med modern datainsamling och analytiska tekniker kan vi integrera mätvärden från träning, prestation och resultat, samt subjektiva och biologiska markörer så att de från en sammantagen bild kan ge rekommendationer anpassade till den specifika individen. Detta gör att idrottarna inte bara kan träna, återhämta sig mer effektivt och prestera bättre, utan även undvika skador och sjukdomar.Artikeln belyser att många professionella team samlar in så mycket mätvärden att de lider av en ”data-tsunami”, och hur den senaste vetenskapen och analytiska metoder, inklusive AI och djupinlärning, kan optimera datainsamling och analys för att minimera skador och förbättra prestationen.
  •  
46.
  • Montenegro, Marcelo F, et al. (författare)
  • Blood Pressure-Lowering Effect of Orally Ingested Nitrite Is Abolished by a Proton Pump Inhibitor.
  • 2017
  • Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 69:1, s. 23-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Inorganic nitrate and nitrite from dietary and endogenous sources are metabolized to NO and other bioactive nitrogen oxides that affect blood pressure. The mechanisms for nitrite bioactivation are unclear, but recent studies in rodents suggest that gastric acidity may influence the systemic effects of this anion. In a randomized, double-blind, placebo-controlled crossover study, we tested the effects of a proton pump inhibitor on the acute cardiovascular effects of nitrite. Fifteen healthy nonsmoking, normotensive subjects, aged 19 to 39 years, were pretreated with placebo or esomeprazole (3×40 mg) before ingesting sodium nitrite (0.3 mg kg(-1)), followed by blood pressure monitoring. Nitrite reduced systolic blood pressure by a maximum of 6±1.3 mm Hg when taken after placebo, whereas pretreatment with esomeprazole blunted this effect. Peak plasma nitrite, nitrate, and nitroso species levels after nitrite ingestion were similar in both interventions. In 8 healthy volunteers, we then infused increasing doses of sodium nitrite (1, 10, and 30 nmol kg(-1) min(-1)) intravenously. Interestingly, although plasma nitrite peaked at similar levels as with orally ingested nitrite (≈1.8 µmol/L), no changes in blood pressure were observed. In rodents, esomeprazole did not affect the blood pressure response to the NO donor, DEA NONOate, or vascular relaxation to nitroprusside and acetylcholine, demonstrating an intact downstream NO-signaling pathway. We conclude that the acute blood pressure-lowering effect of nitrite requires an acidic gastric environment. Future studies will reveal if the cardiovascular complications associated with the use of proton pump inhibitors are linked to interference with the nitrate-nitrite-NO pathway.
  •  
47.
  • Moretti, Chiara, et al. (författare)
  • Dietary nitrite extends lifespan in the fruit fly
  • 2019
  • Ingår i: European Journal of Clinical Investigation,  Vol 49, Suppl 1, p 102, Meeting Abstract: P004-T. - : Wiley-Blackwell. ; 49, s. 102-102
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
  •  
48.
  • Moretti, Chiara H., et al. (författare)
  • Dietary nitrite extends lifespan and prevents age-related locomotor decline in the fruit fly
  • 2020
  • Ingår i: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 160, s. 860-870
  • Tidskriftsartikel (refereegranskat)abstract
    • Aging is associated with decreased nitric oxide (NO) bioavailability and signalling. Boosting of a dietary nitrate nitrite-NO pathway e.g. by ingestion of leafy green vegetables, improves cardiometabolic function, mitochondrial efficiency and reduces oxidative stress in humans and rodents, making dietary nitrate and nitrite an appealing intervention to address age-related disorders. On the other hand, these anions have long been implicated in detrimental health effects of our diet, particularly in formation of carcinogenic nitrosamines.The aim of this study was to assess whether inorganic nitrite affects lifespan in Drosophila melanogaster and investigate possible mechanisms underlying any such effect.In a survival assay, female flies fed a nitrite supplemented diet showed lifespan extension by 9 and 15% with 0.1 and 1 mu M nitrite respectively, with no impact of nitrite on reproductive output. Interestingly, nitrite could also protect female flies from age-dependent locomotor decline, indicating a protective effect on healthspan. NO generation from nitrite involved Drosophila commensal bacteria and was indicated by a fluorescent probe as well as direct measurements of NO gas formation with chemiluminescence.Nutrient sensing pathways such as TOR and sirtuins, have been strongly implicated in lifespan extension. In aged flies, nitrite supplementation significantly downregulated dTOR and upregulated dSir2 gene expression. Total triglycerides and glucose were decreased, a described downstream effect of both TOR and sirtuin pathways.In conclusion, we demonstrate that very low doses of dietary nitrite extend lifespan and favour healthspan in female flies. We propose modulation of nutrient sensing pathways as driving mechanisms for such effects.
  •  
49.
  • Nilsson, Avlant, 1985, et al. (författare)
  • Complex I is bypassed during high intensity exercise
  • 2019
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Human muscles are tailored towards ATP synthesis. When exercising at high work rates muscles convert glucose to lactate, which is less nutrient efficient than respiration. There is hence a trade-off between endurance and power. Metabolic models have been developed to study how limited catalytic capacity of enzymes affects ATP synthesis. Here we integrate an enzyme-constrained metabolic model with proteomics data from muscle fibers. We find that ATP synthesis is constrained by several enzymes. A metabolic bypass of mitochondrial complex I is found to increase the ATP synthesis rate per gram of protein compared to full respiration. To test if this metabolic mode occurs in vivo, we conduct a high resolved incremental exercise tests for five subjects. Their gas exchange at different work rates is accurately reproduced by a whole-body metabolic model incorporating complex I bypass. The study therefore shows how proteome allocation influences metabolism during high intensity exercise.
  •  
50.
  • Nilsson, Lina, et al. (författare)
  • Biphasic relationship between training load and glucose tolerance
  • 2019
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Biphasic relationship between training load and glucose tolerance Nilsson, L, Flockhart M, Bergman K, Apro W, Ekblom B, Larsen FJ There is a well-established construct regarding the positive effects of exercise on glucose tolerance and insulin sensitivity, as well as muscle glycogen storage. In insulin resistance, physical activity is an essential part of the treatment. However, the optimal dose is unknown. Reduced muscular glycogen stores, resulting from exercise, should stimulate an increased uptake of blood glucose. In this study we investigated the relation between training load, glucose tolerance and insulin sensitivity during three weeks of increasing interval training. Three times during the intervention, oral glucose tests were conducted to investigate the rate of glucose uptake. We found a biphasic dose-response relationship between training load and glucose tolerance, where an excessive training load led to a paradoxical reduction in glucose tolerance and impaired insulin release despite an unchanged amount of muscle glycogen. In light of these results, an upper limit of physical exercise exist where the negative effects overpowers the positive.
  •  
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