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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
Nutrition and Dietetics
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: 2019-08-14
Moberg, M. (2018). ACSM Annual Meeting: Två dagar med fokus på muskelhypertrofi/atrofi. Idrottsmedicin, 37(3), 29-31
Open this publication in new window or tab >>ACSM Annual Meeting: Två dagar med fokus på muskelhypertrofi/atrofi
2018 (Swedish)In: Idrottsmedicin, ISSN 2001-3302, Vol. 37, no 3, p. 29-31Article in journal (Other (popular science, discussion, etc.)) Published
Place, publisher, year, edition, pages
Svensk förening för fysisk aktivitet och idrottsmedicin, 2018
National Category
Sport and Fitness Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-5435 (URN)
Available from: 2018-10-16 Created: 2018-10-16 Last updated: 2018-10-16Bibliographically approved
Moberg, M. (2018). Effekt av kombinerad styrke- och konditionsträning. Idrottsmedicin, 37(3), 8-9
Open this publication in new window or tab >>Effekt av kombinerad styrke- och konditionsträning
2018 (Swedish)In: Idrottsmedicin, ISSN 2001-3302, Vol. 37, no 3, p. 8-9Article in journal (Other academic) Published
Abstract [sv]

Det finns teorier om att kombinerad konditions- och styrketräning hämmar styrkeutvecklingen jämfört med enbart styrketräning. För att ta reda på om det stämmer genomfördes studier där cykling kombinerades med styrketräning.

Place, publisher, year, edition, pages
Svensk förening för fysisk aktivitet och idrottsmedicin, 2018
National Category
Sport and Fitness Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-5434 (URN)
Available from: 2018-10-16 Created: 2018-10-16 Last updated: 2018-10-16Bibliographically approved
Lilja, M., Moberg, M., Mandić, M., Gustafsson, T. & Lundberg, T. R. (2018). High versus Low doses of Anti-inflammatory Drugs Do Not Differentially Affect Muscle Molecular Response to Acute Resistance Exercise: 2008 Board #269 May 31 2:00 PM - 3:30 PM.. In: Medicine & Science in Sports & Exercise. 2018 Supplement 1, Vol. 50, p488-488: . Paper presented at ACSM 65th Annual meeting, May 2018 Minneapolis (pp. 488-488). , 50
Open this publication in new window or tab >>High versus Low doses of Anti-inflammatory Drugs Do Not Differentially Affect Muscle Molecular Response to Acute Resistance Exercise: 2008 Board #269 May 31 2:00 PM - 3:30 PM.
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2018 (English)In: Medicine & Science in Sports & Exercise. 2018 Supplement 1, Vol. 50, p488-488, 2018, Vol. 50, p. 488-488Conference paper, Oral presentation with published abstract (Other academic)
National Category
Sport and Fitness Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-5509 (URN)10.1249/01.mss.0000536687.38475.2c (DOI)000456870502129 ()
Conference
ACSM 65th Annual meeting, May 2018 Minneapolis
Available from: 2018-12-20 Created: 2018-12-20 Last updated: 2019-03-19Bibliographically approved
Moberg, M., Apró, W., Ekblom, B., Gerrit, v. H., Holmberg, H.-C. & Blomstrand, E. (2016). Activation of mTORC1 by leucine is potentiated by branched chain amino acids and even more so by essential amino acids following resistance exercise. American Journal of Physiology - Cell Physiology, 310(11), C874-C884
Open this publication in new window or tab >>Activation of mTORC1 by leucine is potentiated by branched chain amino acids and even more so by essential amino acids following resistance exercise
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2016 (English)In: American Journal of Physiology - Cell Physiology, ISSN 0363-6143, E-ISSN 1522-1563, Vol. 310, no 11, p. C874-C884Article in journal (Refereed) Published
Abstract [en]

Protein synthesis is stimulated by resistance exercise and intake of amino acids, in particular leucine. Moreover, activation of mTORC1 signaling by leucine is potentiated by the presence of other essential amino acids (EAA). However, the contribution of the branched-chain amino acids (BCAA) to this effect is yet unknown. Here we compare the stimulatory role of leucine, BCAA and EAA ingestion on anabolic signaling following exercise. Accordingly, eight trained volunteers completed four sessions of resistance exercise during which they ingested either placebo, leucine, BCAA or EAA (including the BCAA) in random order. Muscle biopsies were taken at rest, immediately after exercise and following 90 and 180 min of recovery. Following 90 min of recovery the activity of S6K1 was greater than at rest in all four trials (Placebo<Leucine<BCAA<EAA; P<0.05 time x supplement), with a 9-fold increase in the EAA trial. At this same time-point phosphorylation of 4E-BP1 at Thr37/46 was unaffected by supplementation, while that of Thr46 alone exhibited a pattern similar to that of S6K1, being 18% higher with EAA than BCAA. However, after 180 min of recovery this difference between EAA and BCAA had disappeared, although with both these supplements the increases were still higher than with leucine (40%, P<0.05) and placebo (100%, P<0.05). In summary, EAA ingestion appears to stimulate translation initiation more effectively than the other supplements, although the results also suggest that this effect is primarily attributable to the BCAA.

Keywords
4E-BP1, p70S6 kinase 1, BCAA, skeletal muscle
National Category
Physiology
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-4369 (URN)10.1152/ajpcell.00374.2015 (DOI)000384745400004 ()
Funder
Swedish National Centre for Research in Sports
Note

At the time of Marcus Moberg's disertation this manuscript was submitted.

Available from: 2016-03-01 Created: 2016-03-01 Last updated: 2018-01-10Bibliographically 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
Moberg, M. (2016). Effects of exercise and amino acid intake on mechanisms regulating protein synthesis and breakdown in human muscle. (Doctoral dissertation). Stockholm: Gymnastik- och idrottshögskolan
Open this publication in new window or tab >>Effects of exercise and amino acid intake on mechanisms regulating protein synthesis and breakdown in human muscle
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Skeletal muscle adapts differently to specific modes of exercise, where resistance training results in muscle growth and endurance training induces mitochondrial biogenesis. These are results of molecular events that occur after each exercise session, increasing the expression of specific genes and the rate of both synthesis and breakdown of protein. The rate of protein synthesis is controlled by the mTORC1 signaling pathway, which is potently stimulated by resistance exercise and amino acid, and their combined effect is needed for muscle growth. The essential amino acids (EAA) are responsible for the stimulation of protein synthesis and here leucine has been attributed specific attention, but its particular role among the EAA, and the involvement of the other branched-chain amino acids (BCAA) is unclear. Endurance exercise activates the protein AMPK which, in animal models, has been shown to inhibit mTORC1 signaling and protein synthesis.  Suggesting that concurrent endurance and resistance exercise could restrain muscle growth, but it is unknown if this mechanism is relevant in exercising human muscle. Little is known about the regulation of protein breakdown and although much attention has been given the proteins MuRF-1 and MAFbx which target proteins for degradation, their role requires further investigation. The aim of thesis was to address the mentioned uncertainties by examining how different modes of exercise and amino acids affect mTORC1 signaling, protein synthesis and markers of protein breakdown in human muscle.

In study I, the influence of high intensity endurance exercise on subsequent resistance exercised induced mTORC1 signaling was examined. Despite robust activation of AMPK by the endurance exercise there was no inhibition of mTORC1 signaling or protein synthesis during recovery from resistance exercise. Study II utilized a similar set up, but with the difference that resistance exercise was performed with the triceps. The cycling exercise reduced the resistance exercise stimulated mTORC1 signaling immediately after the exercise, but during the recovery period mTORC1 signaling and protein synthesis was similar between trials. Concurrent exercise induced the mRNA expression of MuRF-1 and that of PGC-1α, the master regulator of mitochondrial biogenesis, in both studies, despite that the exercise modes in study II were separated between legs and arms. In study III, the effect of an EAA supplement with or without leucine, in the stimulation of mTORC1 signaling in connection with resistance exercise was examined. Intake of EAA robustly stimulated mTORC1 signaling after exercise, but this was only minor when leucine was excluded from the supplement. In study IV, subjects were supplied with leucine, BCAA, EAA or placebo in a randomized fashion during four sessions of resistance exercise. Leucine alone stimulated mTORC1 signaling after the exercise, but both the amplitude and extent of stimulation was substantially greater with EAA, an effect that was largely mediated by the BCAA as a group.

In conclusion, endurance exercise prior to resistance exercise using the leg or arm muscles does not affect mTORC1 signaling or protein synthesis during the three hour recovery period from exercise, supporting compatibility between resistance- and endurance exercise induced signaling. Concurrent exercise increases the expression of the proteolytic marker MuRF-1 compared to resistance exercise only, which could indicate both and increased demand of cellular adaptive remodeling or a more direct detrimental proteolytic effect. Leucine is crucial among the EAA in the stimulation of mTORC1 signaling after exercise, its effect is however potentiated by intake of the remaining EAA. As a supplement a mixture of EAA must be regarded preferable, although the effect is largely mediated by the BCAA as a group.  

 

Place, publisher, year, edition, pages
Stockholm: Gymnastik- och idrottshögskolan, 2016. p. 109
Series
Avhandlingsserie för Gymnastik- och idrottshögskolan ; 07
Keywords
Resistance exercise, concurrent exericse, leucine, BCAA, mTORC1 signaling, protein synthesis, MuRF-1, PGC-1alpha
National Category
Sport and Fitness Sciences Cell and Molecular Biology
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-4371 (URN)978-91-980862-6-3 (ISBN)
Public defence
2016-04-01, Aulan, Lidingövägen 1, Stockholm, 09:00 (English)
Opponent
Supervisors
Funder
Swedish National Centre for Research in Sports
Available from: 2016-03-01 Created: 2016-03-01 Last updated: 2018-01-10Bibliographically 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
Apro, W., Moberg, M., Ekblom, B., Holmberg, H.-C. & Blomstrand, E. (2016). High intensity interval cycling performed prior to resistance exercise stimulates autophagy signaling. In: Conference program & abstracts: . Paper presented at 2016 APS Intersociety Meeting. The Integrative Biology of Exercise VII. November 2-4 2016, Phoenix, Arizona. (pp. 84-84).
Open this publication in new window or tab >>High intensity interval cycling performed prior to resistance exercise stimulates autophagy signaling
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2016 (English)In: Conference program & abstracts, 2016, p. 84-84Conference paper, Oral presentation with published abstract (Other academic)
National Category
Sport and Fitness Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-4631 (URN)
Conference
2016 APS Intersociety Meeting. The Integrative Biology of Exercise VII. November 2-4 2016, Phoenix, Arizona.
Available from: 2016-11-08 Created: 2016-11-08 Last updated: 2017-03-31
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-3747-0148

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