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Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro

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journal contribution
posted on 04.05.2017, 09:56 by Neil Martin, Mark Turner, R. Farrington, Darren Player, Mark Lewis
The amino acid leucine is thought to be important for skeletal muscle growth by virtue of its ability to acutely activate mTORC1 and enhance muscle protein synthesis, yet little data exist regarding its impact on skeletal muscle size and its ability to produce force. We utilised a tissue engineering approach in order to test whether supplementing culture medium with leucine could enhance mTORC1 signalling, myotube growth and muscle function. Phosphorylation of the mTORC1 target proteins 4EBP-1 and rpS6 and myotube hypertrophy appeared to occur in a dose dependent manner, with 5 and 20mM of leucine inducing similar effects, which were greater than those seen with 1mM. Maximal contractile force was also elevated with leucine supplementation; however although this did not appear to be enhanced with increasing leucine doses, this effect was completely ablated by co-incubation with the mTOR inhibitor rapamycin, showing that the augmented force production in the presence of leucine was mTOR sensitive. Finally, by using electrical stimulation to induce chronic (24 hours) contraction of engineered skeletal muscle constructs, we were able to show that the effects of leucine and muscle contraction are additive, since the two stimuli had cumulative effects on maximal contractile force production. These results extend our current knowledge of the efficacy of leucine as an anabolic nutritional aid showing for the first time that leucine supplementation may augment skeletal muscle functional capacity, and furthermore validates the use of engineered skeletal muscle for highly-controlled investigations into nutritional regulation of muscle physiology.

Funding

This research was supported in part by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. MPL was in part supported by EPSRC grant number EP/L02067X/2 for the duration of this work.

History

School

  • Sport, Exercise and Health Sciences

Published in

Journal of Cellular Physiology

Pages

? - ? (31)

Citation

MARTIN, N.R.W. ... et al, 2017. Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro. Journal of Cellular Physiology, 232 (10), pp.2788–2797

Publisher

Wiley Periodicals, Inc. (© The Authors)

Version

VoR (Version of Record)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution (CC BY 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by/4.0/

Acceptance date

13/04/2017

Publication date

2017

Notes

This is an open access article published by Wiley and made available under the terms of the Creative Commons Attribution Licence, https://creativecommons.org/licenses/by/4.0/.

ISSN

0021-9541

eISSN

1097-4652

Language

en

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