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Effects of exercise and amino acid intake on mechanisms regulating protein synthesis and breakdown in human muscle
Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Eva Blomstrand's research group.ORCID iD: 0000-0003-3747-0148
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. , 109 p.
Series
Avhandlingsserie för Gymnastik- och idrottshögskolan, 07
Keyword [en]
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: urn:nbn:se:gih:diva-4371ISBN: 978-91-980862-6-3 (print)OAI: oai:DiVA.org:gih-4371DiVA: diva2:908118
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: 2016-03-08Bibliographically approved
List of papers
1. Resistance exercise induced S6K1 kinase activity is not inhibited in human skeletal muscle despite prior activation of AMPK by high intensity interval cycling.
Open this publication in new window or tab >>Resistance exercise induced S6K1 kinase activity is not inhibited in human skeletal muscle despite prior activation of AMPK by high intensity interval cycling.
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2015 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 308, no 6, E470-E481 p.Article in journal (Refereed) Published
Abstract [en]

Combining endurance and strength training in the same session has been reported to reduce the anabolic response to the latter form of exercise. The underlying mechanism, based primarily on results from rodent muscle, is proposed to involve AMPK-dependent inhibition of mTORC1 signaling. This hypothesis was tested in eight trained male subjects who in a randomized order performed either resistance exercise only (R) or interval cycling followed by resistance exercise (ER). Biopsies taken from the vastus lateralis before and after endurance exercise and repeatedly after resistance exercise were assessed for glycogen content, kinase activity, protein phosphorylation and gene expression. Mixed muscle fractional synthetic rate was measured at rest and during 3h of recovery using the stable isotope technique. In ER, AMPK activity was elevated immediately after both endurance and resistance exercise (~90%, P<0.05) but was unchanged in R. Thr389 phosphorylation of S6K1 was increased several-fold immediately after exercise (P<0.05) in both trials and increased further throughout recovery. After 90 and 180 min recovery, S6K1 activity was elevated (~55% and ~110%, respectively, P<0.05) and eEF2 phosphorylation was reduced (~55%, P<0.05) with no difference between trials. In contrast, markers for protein catabolism were differently influenced by the two modes of exercise; ER induced a significant increase in gene and protein expression of MuRF1 (P<0.05), which was not observed following R exercise only. In conclusion, cycling-induced elevation in AMPK activity does not inhibit mTORC1 signaling after subsequent resistance exercise, but may instead interfere with the hypertrophic response by influencing key components in protein breakdown.

National Category
Medical and Health Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-3322 (URN)10.1152/ajpendo.00486.2014 (DOI)
Note

At the time of William Apró's dissertation the publication was a manuscript.

Available from: 2014-05-27 Created: 2014-05-27 Last updated: 2017-03-31Bibliographically approved
2. Lower body endurance exercise acutely affects resistance exercise induced transcriptional and translational signalling in the tricpes brachii muscle
Open this publication in new window or tab >>Lower body endurance exercise acutely affects resistance exercise induced transcriptional and translational signalling in the tricpes brachii muscle
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(English)Manuscript (preprint) (Other academic)
Keyword
Concurrent exercise, S6K1 kinase activity, MuRF-1, mTORC1 signaling, muscle protein synthesis
National Category
Medical and Health Sciences
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-4370 (URN)
Funder
Swedish National Centre for Research in Sports
Note

At the time of Marcus Moberg's dissertation this was a manuscript.

Available from: 2016-03-01 Created: 2016-03-01 Last updated: 2016-04-13Bibliographically approved
3. Absence of leucine in an essential amino acid supplement reduces activation of mTORC1 signalling following resistance exercise in young females.
Open this publication in new window or tab >>Absence of leucine in an essential amino acid supplement reduces activation of mTORC1 signalling following resistance exercise in young females.
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2014 (English)In: Applied Physiology, Nutrition and Metabolism, ISSN 1715-5312, Vol. 39, no 2, 183-94 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of the study was to investigate the specific effect of leucine on mTORC1 signalling and amino acid metabolism in connection with resistance exercise. Comparisons were made between ingestion of supplements with and without leucine. Eight young women performed leg press exercise on 2 occasions. In randomized order they received either an aqueous solution of essential amino acids with leucine (EAA) or without leucine (EAA-Leu), given as small boluses throughout the experiment. Muscle biopsies were taken after an overnight fast before exercise and 1 and 3 h postexercise and samples of blood were taken repeatedly during the experiment. Plasma and muscle concentrations of leucine rose 60%-140% (p < 0.05) with EAA and fell 35%-45% (p < 0.05) with the EAA-Leu supplement. In the EAA-trial, plasma and muscle levels of tyrosine (not present in the supplement) and the sum of the EAA were 15%-25% (p < 0.05) lower during recovery. Phosphorylation of mTOR and p70S6k was elevated to a larger extent following 1 h of recovery with leucine in the supplement (120% vs. 49% (p < 0.05) and 59- vs. 8-fold (p < 0.05) for EAA and EAA-Leu, respectively). The levels of MAFbx and MuRF-1 mRNA and of the corresponding proteins were not significantly altered after 3 h recovery from exercise. In conclusion, the presence of leucine in the supplement enhances the stimulatory effect on mTORC1 signalling and reduces the level of tyrosine and the sum of the EAA in muscle and plasma, suggesting a stimulation of protein synthesis and (or) inhibition of breakdown, leading to improvement in net protein balance.

National Category
Physiology
Research subject
Medicine/Technology
Identifiers
urn:nbn:se:gih:diva-3273 (URN)10.1139/apnm-2013-0244 (DOI)24476474 (PubMedID)
Available from: 2014-03-31 Created: 2014-03-31 Last updated: 2017-03-31Bibliographically approved
4. Activation of mTORC1 by leucine is potentiated by branched chain amino acids and even more so by essential amino acids following resistance exercise
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, C874-C884 p.Article 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.

Keyword
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: 2016-12-05Bibliographically approved

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