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Hammarström, D., Øfsteng, S., Koll, L., Hanestadhaugen, M., Hollan, I., Apro, W., . . . Ellefsen, S. (2020). Benefits of higher resistance-training volume are related to ribosome biogenesis.. Journal of Physiology, 598(3), 543-565
Open this publication in new window or tab >>Benefits of higher resistance-training volume are related to ribosome biogenesis.
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2020 (English)In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 598, no 3, p. 543-565Article in journal (Refereed) Published
Abstract [en]

KEY POINTS: For individuals showing suboptimal adaptations to resistance training, manipulation of training volume is a potential measure to facilitate responses. This remains unexplored. Here, 34 untrained individuals performed contralateral resistance training with moderate and low volume for 12 weeks. Moderate volume led to larger increases in muscle cross-sectional area, strength and type II fibre-type transitions. These changes coincided with greater activation of signalling pathways controlling muscle growth and greater induction of ribosome synthesis. Thirteen and sixteen participants, respectively, displayed clear benefits of moderate-volume training on muscle hypertrophy and strength. This coincided with greater total RNA accumulation in the early-phase of the training period, suggesting that ribosomal biogenesis regulates the dose-response relationship between training volume and muscle hypertrophy. These results demonstrate that there is a dose-dependent relationship between training volume and outcomes. On the individual level, benefits of higher training volume were associated with increased ribosomal biogenesis.

ABSTRACT: Resistance-exercise volume is a determinant of training outcomes. However not all individuals respond in a dose-dependent fashion. In this study, 34 healthy individuals (males n = 16, 23.6 (4.1) years; females n = 18, 22.0 (1.3)) performed moderate- (3 sets per exercise, MOD) and low-volume (1 set, LOW) resistance training in a contralateral fashion for 12 weeks (2-3 sessions × week-1 ). Muscle cross-sectional area (CSA) and strength were assessed at weeks 0 and 12, along with biopsy sampling (m. Vastus lateralis). Muscle biopsies were also sampled before and one hour after the fifth session (Week 2). MOD resulted in larger increases in muscle CSA (5.2 (3.8)% versus 3.7 (3.7)%, P < 0.001) and strength (3.4-7.7% difference, all P < 0.05. This coincided with greater reductions in type IIX fibres from week 0 to 12 (MOD, -4.6; LOW -3.2%-point), greater phosphorylation of S6-kinase 1 (p85 S6K1Thr412 , 19%; p70 S6K1Thr389 , 58%) and ribosomal protein S6Ser235/236 (37%), greater rested-state total RNA (8.8%) and greater exercise-induced c-Myc mRNA expression (25%; Week 2, all P < 0.05). Thirteen and sixteen participants, respectively, displayed clear benefits in response to MOD on muscle hypertrophy and strength. Benefits were associated with greater accumulation of total RNA at Week 2 in the MOD leg, with every 1% difference increasing the odds of MOD benefit by 7.0% (P = 0.005) and 9.8% (P = 0.002). In conclusion, MOD led to greater functional and biological adaptations than LOW. Associations between dose-dependent total RNA accumulation and increases in muscle mass and strength points to ribosome biogenesis as a determinant of dose-dependent training responses. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
John Wiley & Sons, 2020
National Category
Physiology
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-5958 (URN)10.1113/JP278455 (DOI)31813190 (PubMedID)
Available from: 2019-12-18 Created: 2019-12-18 Last updated: 2020-02-24Bibliographically approved
Horwath, O., Apro, W., Moberg, M., Godhe, M., Helge, T., Ekblom, M., . . . Ekblom, B. (2020). Fiber type-specific hypertrophy and increased capillarization in skeletal muscle following testosterone administration of young women.. Journal of applied physiology
Open this publication in new window or tab >>Fiber type-specific hypertrophy and increased capillarization in skeletal muscle following testosterone administration of young women.
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2020 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601Article in journal (Refereed) Epub ahead of print
Abstract [en]

It is well established that testosterone administration induces muscle fiber hypertrophy and myonuclear addition in men, however, it remains to be determined whether similar morphological adaptations can be achieved in women. The aim of the present study was therefore to investigate whether exogenously administered testosterone alters muscle fiber morphology in skeletal muscle of young healthy, physically active women. Thirty-five young (20-35 years), recreationally trained women were randomly assigned to either 10-week testosterone administration (10 mg daily) or placebo. Before and after the intervention, hormone concentrations and body composition were assessed, and muscle biopsies were obtained from the vastus lateralis. Fiber type composition, fiber size, satellite cell- and myonuclei content, as well as muscle capillarization were assessed in a fiber type-specific manner using immunohistochemistry. Following the intervention, testosterone administration elevated serum testosterone concentration (5.1-fold increase, P=0.001), and induced significant accretion of total lean mass (+1.9%, P=0.002) and leg lean mass (+2.4%, P=0.001). On the muscle fiber level, testosterone increased mixed fiber cross-sectional area (+8.2%, P=0.001), an effect primarily driven by increases in type II fiber size (9.2%, P=0.006). Whereas myonuclei content remained unchanged, a numerical increase (+30.8%) was found for satellite cells associated with type II fibers in the Testosterone group. In parallel with fiber hypertrophy, testosterone significantly increased capillary contacts (+7.5%, P=0.015) and capillary-to-fiber ratio (+9.2%, P=0.001) in type II muscle fibers. The current study provides novel insight into fiber type-specific adaptations present already after 10 weeks of only moderately elevated testosterone levels in women.

Place, publisher, year, edition, pages
American Physiological Society, 2020
Keywords
androgens, capillarization, myonuclear domain, myonuclei, satellite cells
National Category
Physiology
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-6096 (URN)10.1152/japplphysiol.00893.2019 (DOI)32191598 (PubMedID)
Available from: 2020-03-24 Created: 2020-03-24 Last updated: 2020-03-26Bibliographically approved
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
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
Horwath, O., Granberg, J. & Apro, W. (2019). Low Glycogen Availability Increases Autophagy Signalling Following Resistance Exercise. In: : . Paper presented at European College of Sport Science ECSS 2019, Prague 3-6 July.
Open this publication in new window or tab >>Low Glycogen Availability Increases Autophagy Signalling Following Resistance Exercise
2019 (English)Conference paper, Poster (with or without abstract) (Other academic)
National Category
Health Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-6097 (URN)
Conference
European College of Sport Science ECSS 2019, Prague 3-6 July
Funder
Swedish National Centre for Research in Sports, P2018-0161
Available from: 2020-03-25 Created: 2020-03-25 Last updated: 2020-03-26Bibliographically approved
Edman, S., Söderlund, K., Moberg, M., Apro, W. & Blomstrand, E. (2019). mTORC1 Signaling in Individual Human Muscle Fibers Following Resistance Exercise in Combination With Intake of Essential Amino Acids. Frontiers in nutrition, 6, Article ID 96.
Open this publication in new window or tab >>mTORC1 Signaling in Individual Human Muscle Fibers Following Resistance Exercise in Combination With Intake of Essential Amino Acids
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2019 (English)In: Frontiers in nutrition, ISSN 2296-861X, Vol. 6, article id 96Article in journal (Refereed) Published
Abstract [en]

Human muscles contain a mixture of type I and type II fibers with different contractile and metabolic properties. Little is presently known about the effect of anabolic stimuli, in particular nutrition, on the molecular responses of these different fiber types. Here, we examine the effect of resistance exercise in combination with intake of essential amino acids (EAA) on mTORC1 signaling in individual type I and type II human muscle fibers. Five strength-trained men performed two sessions of heavy leg press exercise. During exercise and recovery, the subjects ingested an aqueous solution of EAA (290 mg/kg) or flavored water (placebo). Muscle biopsies were taken from the vastus lateralis before and 90 min after exercise. The biopsies were freeze-dried and single fibers dissected out and weighed (range 0.95-8.1 mu g). The fibers were homogenized individually and identified as type I or II by incubation with antibodies against the different isoforms of myosin. They were also analyzed for both the levels of protein as well as phosphorylation of proteins in the mTORC1 pathway using Western blotting. The levels of the S6K1 and eEF2 proteins were similar to 50% higher in type II than in type I fibers (P < 0.05), but no difference was found between fiber types with respect to the level of mTOR protein. Resistance exercise led to non-significant increases (2-3-fold) in mTOR and S6K1 phosphorylation as well as a 50% decrease (P < 0.05) in eEF2 phosphorylation in both fiber types. Intake of EAA caused a 2 and 6-fold higher (P < 0.05) elevation of mTOR and S6K1 phosphorylation, respectively, in both type I and type II fibers compared to placebo, with no effect on phosphorylation of eEF2. In conclusion, protein levels of S6K1 and eEF2 were significantly higher in type II than type I fibers suggesting higher capacity of the mTOR pathway in type II fibers. Ingestion of EAA enhanced the effect of resistance exercise on phosphorylation of mTOR and S6K1 in both fiber types, but with considerable variation between single fibers of both types.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019
Keywords
muscle fiber type, protein expression, S6K1, single muscle fiber, EAA
National Category
Physiology
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-5807 (URN)10.3389/fnut.2019.00096 (DOI)000472610200002 ()31294029 (PubMedID)
Available from: 2019-08-14 Created: 2019-08-14 Last updated: 2019-12-05
Blomstrand, E. & Apro, W. (2018). Det viktigaste du behöver veta om protein och träning. Idrottsforskning.se, Article ID 30 maj.
Open this publication in new window or tab >>Det viktigaste du behöver veta om protein och träning
2018 (Swedish)In: Idrottsforskning.se, ISSN 2002-3944, article id 30 majArticle in journal (Other (popular science, discussion, etc.)) Published
Place, publisher, year, edition, pages
Stockholm: Centrum för idrottsforskning, CIF, 2018
National Category
Sport and Fitness Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-5443 (URN)
Available from: 2018-10-16 Created: 2018-10-16 Last updated: 2018-10-17Bibliographically approved
Rundqvist, H. C., Esbjörnsson, M., Rooyackers, O., Apro, W., Moberg, M., Österlund, T. & Jansson, E. (2016). Amino Acid Transport after Sprint Exercise and Oral Amino Acids: 90 Board #6 June 1, 9. In: Medicine & Science in Sports & Exercise: Volume 48(5S) Supplement 1, May 2016, p 5: . Paper presented at American College of Sports Medicine (ACSM) 63rd Annual Meeting, May 31-June 4 2016, Boston (pp. 5). , 48(5 Suppl 1)
Open this publication in new window or tab >>Amino Acid Transport after Sprint Exercise and Oral Amino Acids: 90 Board #6 June 1, 9
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2016 (English)In: Medicine & Science in Sports & Exercise: Volume 48(5S) Supplement 1, May 2016, p 5, 2016, Vol. 48, no 5 Suppl 1, p. 5-Conference paper, Published paper (Other academic)
Abstract [en]

PURPOSE: To study if oral ingestion of essential amino acids (oral EAA) increases the amino acid transporter SNAT2, Akt/mTOR signaling and muscle protein synthesis (MPS) after sprint exercise.

METHODS: 12 healthy subjects performed three 30-s sprints with 20 minutes rest in between. Subjects consumed EAA + maltodextrin solution or flavoured water (placebo) during the sprint exercise up to 15 min after the last sprint in a randomized order with one month interval. In vivo MPS rate was measured using a stable isotope technique. Subject received a stable isotope of phenylalanine (D5-phenylalanine) to label the precursor pool for protein synthesis. Continuous infusion started before the first sprint and was ended 200 min after the last sprint. Two post exercise biopsies (vastus lateralis) were obtained 80 min and 200 min after last sprint. The amount of labelled phenylalanine incorporated into muscle protein over these 2 hours represents the in vivo MPS rate and was expressed as fractional synthesis rate (FSR %) calculated by dividing amount of labelled phenylalanine incorporated during these 2 hours by the amount in the free amino acid (precursor) plasma pool. Biopsies were also analyzed for Akt/mTOR signaling and SNAT2 amino acid transporter by Western blot and for SNAT2 gene expression by real-time PCR. Blood samples were analyzed for amino acids, glucose, lactate, and insulin. Four subjects, involuntary vomiting after exercise during EAA condition, showed a minor increase in plasma leucine and were presented separately.

RESULTS: Non-vomiting subjects (n=8): The expression of the amino acid transporter SNAT2 was higher both at the protein (P<0.05) and the mRNA (P<0.001) level after EEA than after placebo. Fold increase for phosphorylated Akt, mTOR and p70 was 1.7-3.6 (P<0.01 - P<0.001) comparing EAA with placebo. FSR % after EEA was increased by 25 % (P=0.02) compared to placebo. None of these variables were significantly increased in the subjects who vomited.

CONCLUSION: Oral EAA increased MPS after sprint exercise. Enhanced capacity for amino acid transport and subsequent enhanced Akt/mTOR signaling are suggested to mediate the increased MPS.

National Category
Sport and Fitness Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-4566 (URN)10.1249/01.mss.0000485021.31770.d3 (DOI)27584180 (PubMedID)
Conference
American College of Sports Medicine (ACSM) 63rd Annual Meeting, May 31-June 4 2016, Boston
Available from: 2016-09-15 Created: 2016-09-15 Last updated: 2016-09-16Bibliographically approved
Apró, W., Moberg, M., Holmberg, H.-C. & Blomstrand, E. (2016). Amino Acid-induced S6K1 Activity In Human Skeletal Muscle Is Mediated By Increased mTor/Rheb Interaction: 128 June 1, 11: 15 AM - 11: 30 AM.. In: Medicine And Science In Sports And Exercise 2016 May; Vol. 48 (5S Suppl 1), pp. 17.: (pp. 17-17). , 48(5S Suppl 1)
Open this publication in new window or tab >>Amino Acid-induced S6K1 Activity In Human Skeletal Muscle Is Mediated By Increased mTor/Rheb Interaction: 128 June 1, 11: 15 AM - 11: 30 AM.
2016 (English)In: Medicine And Science In Sports And Exercise 2016 May; Vol. 48 (5S Suppl 1), pp. 17., 2016, Vol. 48, no 5S Suppl 1, p. 17-17Conference paper, Published paper (Refereed)
Abstract [en]

Cell culture studies have shown that amino acids activate mTORC1 signaling by increasing the interaction between mTOR and its essential activator Rheb. However, the existence of this mechanism in human skeletal muscle remains to be determined.

PURPOSE: To determine if increased mTORC1 signaling in response to amino acids in human skeletal muscle is due to an increased interaction between mTOR and Rheb.

METHODS: Eight well trained men performed resistance exercise on two separate occasions. In connection with the exercise, subjects were supplemented with flavored water (Pla) and essential amino acids (EAA) in a double-blind, randomized cross-over design. Muscle biopsies were taken in the vastus lateralis muscle before, immediately after and 90 and 180 min post exercise. Activity of the mTORC1 pathway was assessed by a radiolabeled in-vitro kinase assay for its immediate downstream target S6K1. Protein-protein interactions were determined by western blot following co-immunoprecipitation of mTOR with Rheb. Co-immunoprecipitation was performed on pooled muscle samples from three of the eight subjects.

RESULTS: Activity of S6K1 remained unchanged immediately after exercise in both trials. However, at 90 min post exercise, S6K1 activity increased by approximately 2- and 8-fold (p<0.05) from baseline the Pla and EAA trials, respectively. At the 180 min time point, S6K1 activity remained elevated in both trials being approx. 3-fold higher in the Pla trial and 5-fold higher (p<0.05) in the EAA trial. The fold-change in mTOR and Rheb interaction largely resembled the activity pattern of S6K1 in both trials; in the Pla trial the fold-change was 0.9, 1.3 and 1.4 while in the EAA trial the fold-change was 1.6, 2.9 and 1.9 immediately after, 90 min after and 180 min after exercise, respectively.

CONCLUSIONS: The large increase in S6K1 activity following EAA intake appears to be mediated by an increased interaction between mTOR and its proximal activator Rheb. This is the first time this mechanism has been demonstrated in human skeletal muscle.

National Category
Sport and Fitness Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-4514 (URN)
Available from: 2016-08-05 Created: 2016-08-05 Last updated: 2016-08-08Bibliographically approved
Kazior, Z., Willis, S. J., Moberg, M., Apró, W., Calbet, J. A., Holmberg, H.-C. & Blomstrand, E. (2016). Endurance Exercise Enhances the Effect of Strength Training on Muscle Fiber Size and Protein Expression of Akt and mTOR.. PLoS ONE, 11(2), Article ID e0149082.
Open this publication in new window or tab >>Endurance Exercise Enhances the Effect of Strength Training on Muscle Fiber Size and Protein Expression of Akt and mTOR.
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 2, article id e0149082Article in journal (Refereed) Published
Abstract [en]

Reports concerning the effect of endurance exercise on the anabolic response to strength training have been contradictory. This study re-investigated this issue, focusing on training effects on indicators of protein synthesis and degradation. Two groups of male subjects performed 7 weeks of resistance exercise alone (R; n = 7) or in combination with preceding endurance exercise, including both continuous and interval cycling (ER; n = 9). Muscle biopsies were taken before and after the training period. Similar increases in leg-press 1 repetition maximum (30%; P<0.05) were observed in both groups, whereas maximal oxygen uptake was elevated (8%; P<0.05) only in the ER group. The ER training enlarged the areas of both type I and type II fibers, whereas the R protocol increased only the type II fibers. The mean fiber area increased by 28% (P<0.05) in the ER group, whereas no significant increase was observed in the R group. Moreover, expression of Akt and mTOR protein was enhanced in the ER group, whereas only the level of mTOR was elevated following R training. Training-induced alterations in the levels of both Akt and mTOR protein were correlated to changes in type I fiber area (r = 0.55-0.61, P<0.05), as well as mean fiber area (r = 0.55-0.61, P<0.05), reflecting the important role played by these proteins in connection with muscle hypertrophy. Both training regimes reduced the level of MAFbx protein (P<0.05) and tended to elevate that of MuRF-1. The present findings indicate that the larger hypertrophy observed in the ER group is due more to pronounced stimulation of anabolic rather than inhibition of catabolic processes.

National Category
Sport and Fitness Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-4363 (URN)10.1371/journal.pone.0149082 (DOI)000371218400061 ()26885978 (PubMedID)
Available from: 2016-02-24 Created: 2016-02-24 Last updated: 2017-11-30Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0003-1942-2919

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