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Absence of leucine in an essential amino acid supplement reduces activation of mTORC1 signalling following resistance exercise in young females.
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
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: 0000-0003-1942-2919
Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
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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.

Place, publisher, year, edition, pages
2014. Vol. 39, no 2, 183-94 p.
National Category
Research subject
URN: urn:nbn:se:gih:diva-3273DOI: 10.1139/apnm-2013-0244PubMedID: 24476474OAI: diva2:708932
Available from: 2014-03-31 Created: 2014-03-31 Last updated: 2016-06-20Bibliographically approved
In thesis
1. Effects of exercise and amino acid intake on mechanisms regulating protein synthesis and breakdown in human muscle
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. 109 p.
Avhandlingsserie för Gymnastik- och idrottshögskolan, 07
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
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)
Swedish National Centre for Research in Sports
Available from: 2016-03-01 Created: 2016-03-01 Last updated: 2016-03-08Bibliographically approved

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Moberg, MarcusApró, WilliamPontén, MarjanEkblom, BjörnBlomstrand, Eva
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