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Regulation of Amino Acid Transporters and Sensors in Response to a High protein Diet: A Randomized Controlled Trial in Elderly Men

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The journal of nutrition, health & aging

Abstract

Background

The mammalian target of rapamycin complex 1 (mTORC1) is fundamental for many cellular processes, yet it is often dysregulated with aging. Increased amino acid (AA) availability is correlated with the expression of AA transporters (AAT) and mTORC1 activity. Although many AA sensors and mediators have been proposed to relay the AA signal to mTORC1, it has not yet been determined if chronic dietary intervention affects the expression of AAT, sensors and mediators and their relationships with mTORC1 activity.

Objective and Design

This study investigated whether the consumption of a diet containing either the current recommended daily allowance (RDA) of protein intake (0.8 g/kg/d) or twice the RDA (2RDA) for ten weeks affected the expression of targets associated with AA transport, sensing and mTORC1 regulation in 26 older men (70-81 years).

Method

Muscle biopsies were collected before and after the intervention under fasting conditions. Diets were controlled by providing fully prepared meals and snacks. Western blot and quantitative polymerase chain reaction were used to measure protein and gene expression respectively.

Results

Consumption of 2RDA reduced the protein expression of L-type amino acid transporter 1 (LAT1). However, plasma leucine concentration and basal mTORC1 activity were unaltered. The downregulation of LAT1 did not affect the expression of AA sensors and mediators, including leucyl tRNA synthetase (LRS), cytosolic arginine sensor for mTORC1 (CASTOR1), Sestrin2 and Rag proteins. Instead, total ribosomal protein S6 (RPS6) was upregulated with 2RDA.

Conclusion

Ten weeks of 2RDA diet did not affect the fasting mTORC1 signaling, but increased total RPS6 might suggest improved muscular translational capacity to maintain muscular mass.

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Authors and Affiliations

  1. Liggins Institute, The University of Auckland, Private Bag 92019, Victoria Street West, Auckland, 1142, New Zealand

    N. Zeng, U. Prodhan, R. F. d’Souza, F. Ramzan, S. M. Mitchell, P. Sharma, A. M. Milan, D. Cameron-Smith & Cameron J. Mitchell

  2. Department of Food Technology and Nutritional Science, Mawlana Bhashani Science and Technology University, Tangail, 1902, Bangladesh

    U. Prodhan

  3. Food Nutrition & Health Team, AgResearch, Palmerston North, 4474, New Zealand

    S. O. Knowles & N. C. Roy

  4. Food & Bio-based Products Group, AgResearch, Palmerston North, 4474, New Zealand

    D. Cameron-Smith

  5. Riddet Institute, Palmerston North, 4442, New Zealand

    N. C. Roy & D. Cameron-Smith

  6. Department of Nutrition, Exercise and Sport, Copenhagen University, Copenhagen, Denmark

    A. Sjödin

  7. Department of Nutritional Sciences and Research Platform Active Aging, University of Vienna, Vienna, Austria

    K.-H. Wagner

  8. Faculty of Education, School of Kinesiology, The University of British Columbia, Vancouver Campus, 2553 Wesbrook Mall, Vancouver, British Columbia, V6T 1Z3, Canada

    Cameron J. Mitchell

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  1. N. Zeng
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  2. U. Prodhan
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  3. R. F. d’Souza
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  4. F. Ramzan
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  11. A. M. Milan
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  12. D. Cameron-Smith
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  13. Cameron J. Mitchell
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Correspondence to Cameron J. Mitchell.

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Zeng, N., Prodhan, U., d’Souza, R.F. et al. Regulation of Amino Acid Transporters and Sensors in Response to a High protein Diet: A Randomized Controlled Trial in Elderly Men. J Nutr Health Aging 23, 354–363 (2019). https://doi.org/10.1007/s12603-019-1171-4

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  • DOI: https://doi.org/10.1007/s12603-019-1171-4

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