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Publications (10 of 31) Show all publications
Nilsson, L., Flockhart, M., Apro, W., Ekblom, B. & Larsen, F. J. (2019). Biphasic relationship between training load and glucose tolerance. In: : . Paper presented at Cell Symposia, Exercise Metabolism. May 5-7 2019, Sitges Spain.
Open this publication in new window or tab >>Biphasic relationship between training load and glucose tolerance
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2019 (English)Conference paper, Poster (with or without abstract) (Other academic)
Abstract [sv]

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.

National Category
Cell Biology
Research subject
Medicine/Technology; Medicine/Technology; Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-5933 (URN)
Conference
Cell Symposia, Exercise Metabolism. May 5-7 2019, Sitges Spain
Funder
Swedish National Centre for Research in Sports
Available from: 2019-11-29 Created: 2019-11-29 Last updated: 2019-12-09Bibliographically approved
Nilsson, A., Björnson, E., Flockhart, M., Larsen, F. J. & Nielsen, J. (2019). Complex I is bypassed during high intensity exercise.. Nature Communications, 10(1), Article ID 5072.
Open this publication in new window or tab >>Complex I is bypassed during high intensity exercise.
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2019 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, no 1, article id 5072Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Sport and Fitness Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-5909 (URN)10.1038/s41467-019-12934-8 (DOI)000494938600006 ()31699973 (PubMedID)
Available from: 2019-11-11 Created: 2019-11-11 Last updated: 2019-12-19
Moretti, C., Larsen, F. J. & Lundberg, J. (2019). Dietary nitrite extends lifespan in the fruit fly. In: European Journal of Clinical Investigation,  Vol 49, Suppl 1, p 102, Meeting Abstract: P004-T: . Paper presented at 53rd Annual Scientific Meeting of the European Society for Clinical Investigation “The Clocks of Metabolism and Disease”, Coimbra, Portugal, 22nd – 24th May 2019 (pp. 102-102). Wiley-Blackwell, 49
Open this publication in new window or tab >>Dietary nitrite extends lifespan in the fruit fly
2019 (English)In: European Journal of Clinical Investigation,  Vol 49, Suppl 1, p 102, Meeting Abstract: P004-T, Wiley-Blackwell, 2019, Vol. 49, p. 102-102Conference paper, Oral presentation with published abstract (Other academic)
Place, publisher, year, edition, pages
Wiley-Blackwell, 2019
National Category
Nutrition and Dietetics
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-5778 (URN)000466956400195 ()
Conference
53rd Annual Scientific Meeting of the European Society for Clinical Investigation “The Clocks of Metabolism and Disease”, Coimbra, Portugal, 22nd – 24th May 2019
Available from: 2019-06-14 Created: 2019-06-14 Last updated: 2019-06-14Bibliographically approved
Flockhart, M., Nilsson, L., Apro, W., Ekblom, B. & Larsen, F. J. (2019). Dose-response relationship between exercise load and mitochondrial function. In: : . Paper presented at Cell Symposia: Exercise Metabolism, May 5-7 2019, Sitges Spain.
Open this publication in new window or tab >>Dose-response relationship between exercise load and mitochondrial function
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2019 (English)Conference paper, Poster (with or without abstract) (Other academic)
Abstract [en]

Dose-response relationship between exercise load and mitochondrial function

Flockhart M, Nilsson L, Bergman K, Apro W, Ekblom B, Larsen FJ

A 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.

National Category
Cell Biology
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-5932 (URN)
Conference
Cell Symposia: Exercise Metabolism, May 5-7 2019, Sitges Spain
Funder
Swedish National Centre for Research in Sports
Available from: 2019-11-29 Created: 2019-11-29 Last updated: 2019-12-09Bibliographically approved
Cardinale, D. A., Larsen, F. J., Lindholm, P., Ekblom, B. & Boushel, R. (2019). Effects Of Hyperoxic-Supplemented High Intensity Interval Training On Endurance Performance, Maximal Oxygen Consumption And Mitochondrial Function In Trained Cyclists. In: MEDICINE AND SCIENCE IN SPORTS AND EXERCISE Vol 51(2019):6. Supplement: S, Meeting Abstract: 1753: . Paper presented at Annual Meeting of the American-College-of-Sports-Medicine (ACSM), MAY 28-JUN 01, 2019, Orlando, FL (pp. 463-464). Lippincott Williams & Wilkins, 51(6)
Open this publication in new window or tab >>Effects Of Hyperoxic-Supplemented High Intensity Interval Training On Endurance Performance, Maximal Oxygen Consumption And Mitochondrial Function In Trained Cyclists
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2019 (English)In: MEDICINE AND SCIENCE IN SPORTS AND EXERCISE Vol 51(2019):6. Supplement: S, Meeting Abstract: 1753, Lippincott Williams & Wilkins, 2019, Vol. 51, no 6, p. 463-464Conference paper, Oral presentation with published abstract (Other academic)
Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2019
National Category
Sport and Fitness Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-5836 (URN)10.1249/01.mss.0000561892.45529.46 (DOI)000481662801604 ()
Conference
Annual Meeting of the American-College-of-Sports-Medicine (ACSM), MAY 28-JUN 01, 2019, Orlando, FL
Available from: 2019-09-17 Created: 2019-09-17 Last updated: 2019-09-17Bibliographically approved
Cardinale, D. A., Larsen, F. J., Lännerström, J., Manselin, T., Södergård, O., Mijwel, S., . . . Boushel, R. (2019). Influence of Hyperoxic-Supplemented High-Intensity Interval Training on Hemotological and Muscle Mitochondrial Adaptations in Trained Cyclists.. Frontiers in Physiology, 10, Article ID 730.
Open this publication in new window or tab >>Influence of Hyperoxic-Supplemented High-Intensity Interval Training on Hemotological and Muscle Mitochondrial Adaptations in Trained Cyclists.
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2019 (English)In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 730Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019
Keywords
OXPHOS, VO2max, cycling performance, high-intensity interval training, hyperoxia, mitochondria
National Category
Sport and Fitness Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-5805 (URN)10.3389/fphys.2019.00730 (DOI)000472046700001 ()31258485 (PubMedID)
Available from: 2019-08-14 Created: 2019-08-14 Last updated: 2019-08-14Bibliographically approved
Cardinale, D. A., Larsen, F. J., Jensen-Urstad, M., Rullman, E., Søndergaard, H., Morales-Alamo, D., . . . Boushel, R. (2019). Muscle mass and inspired oxygen influence oxygen extraction at maximal exercise: role of mitochondrial oxygen affinity.. Acta Physiologica, 225(1), Article ID e13110.
Open this publication in new window or tab >>Muscle mass and inspired oxygen influence oxygen extraction at maximal exercise: role of mitochondrial oxygen affinity.
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2019 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 225, no 1, article id e13110Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2019
Keywords
OXPHOS, VO2max, Fick method, hyperoxia, mitochondrial p50, muscle O2 diffusion, thermodilution technique
National Category
Sport and Fitness Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-5287 (URN)10.1111/apha.13110 (DOI)000454605500006 ()29863764 (PubMedID)
Available from: 2018-06-07 Created: 2018-06-07 Last updated: 2019-01-18Bibliographically approved
Flockhart, M. & Larsen, F. J. (2019). Physiological adaptation of aerobic efficiency: when less is more. [Letter to the editor]. Journal of applied physiology, 127(6), Article ID 1821.
Open this publication in new window or tab >>Physiological adaptation of aerobic efficiency: when less is more.
2019 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 127, no 6, article id 1821Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
American Physiological Society, 2019
National Category
Sport and Fitness Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-5961 (URN)10.1152/japplphysiol.00649.2019 (DOI)000504408200042 ()31829830 (PubMedID)
Available from: 2019-12-18 Created: 2019-12-18 Last updated: 2020-01-09Bibliographically approved
Cardinale, D. A., Larsen, F. J., Schiffer, T. A., Morales-Alamo, D., Ekblom, B., Calbet, J. A., . . . Boushel, R. (2018). Superior Intrinsic Mitochondrial Respiration in Women Than in Men.. Frontiers in Physiology, 9, Article ID 1133.
Open this publication in new window or tab >>Superior Intrinsic Mitochondrial Respiration in Women Than in Men.
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2018 (English)In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 1133Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
OXPHOS, endurance performance, mitochondria, mitochondrial function, sexual dimorphism, skeletal muscle
National Category
Sport and Fitness Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-5407 (URN)10.3389/fphys.2018.01133 (DOI)000441955000001 ()30174617 (PubMedID)
Available from: 2018-09-04 Created: 2018-09-04 Last updated: 2018-10-17Bibliographically approved
Manselin, T. A., Södergård, O., Larsen, F. J. & Lindholm, P. (2017). Aerobic efficiency is associated with the improvement in maximal power output during acute hyperoxia.. Physiological Reports, 5(2), Article ID e13119.
Open this publication in new window or tab >>Aerobic efficiency is associated with the improvement in maximal power output during acute hyperoxia.
2017 (English)In: Physiological Reports, E-ISSN 2051-817X, Vol. 5, no 2, article id e13119Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Physiology
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-4764 (URN)10.14814/phy2.13119 (DOI)000393855700011 ()28108650 (PubMedID)
Available from: 2017-02-01 Created: 2017-02-01 Last updated: 2018-01-13
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-1343-8656

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