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Muscle full effect after oral protein: time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling.
Am J Clin Nutr. 2010 Nov; 92(5):1080-8.AJ

Abstract

BACKGROUND

We previously showed that human muscle protein synthesis (MPS) increased during infusion of amino acids (AAs) and peaked at ≈120 min before returning to baseline rates, despite elevated plasma AA concentrations.

OBJECTIVE

We tested whether a protein meal elicited a similar response and whether signaling responses that regulate messenger RNA translation matched MPS changes.

DESIGN

Eight postabsorptive healthy men (≈21 y of age) were studied during 8.5 h of primed continuous infusion of [1,2-¹³C₂]leucine with intermittent quadriceps biopsies for determination of MPS and anabolic signaling. After 2.5 h, subjects consumed 48 g whey protein.

RESULTS

At 45-90 min after oral protein bolus, mean (± SEM) myofibrillar protein synthesis increased from 0.03 ± 0.003% to 0.10 ± 0.01%/h; thereafter, myofibrillar protein synthesis returned to baseline rates even though plasma essential AA (EAA) concentrations remained elevated (+130% at 120 min, +80% at 180 min). The activity of protein kinase B (PKB) and phosphorylation of eukaryotic initiation factor 4G preceded the rise of MPS and increases in phosphorylation of ribosomal protein kinase S6 (S6K1), and 4E-binding protein 1 (4EBP1) was superimposable with MPS responses until 90 min. However, although MPS decreased thereafter, all signals, with the exception of PKB activity (which mirrored insulin responses), remained elevated, which echoed the slowly declining plasma EAA profile. The phosphorylation of eukaryotic initiation factor 2α increased only at 180 min. Thus, discordance existed between MPS and the mammalian target of rapamycin complex 1 (mTORC1) and signaling (ie, S6K1 and 4EBP1 phosphorylation).

CONCLUSIONS

We confirm our previous findings that MPS responses to AAs are transient, even with oral protein bolus. However, changes in MPS only reflect elevated mTORC1 signaling during the upswing in MPS.

Authors+Show Affiliations

School of Graduate Entry Medicine and Health, Division of Clinical Physiology, University of Nottingham, Royal Derby Hospital, Derby, United Kingdom. philip.atherton@nottingham.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20844073

Citation

Atherton, Philip J., et al. "Muscle Full Effect After Oral Protein: Time-dependent Concordance and Discordance Between Human Muscle Protein Synthesis and mTORC1 Signaling." The American Journal of Clinical Nutrition, vol. 92, no. 5, 2010, pp. 1080-8.
Atherton PJ, Etheridge T, Watt PW, et al. Muscle full effect after oral protein: time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling. Am J Clin Nutr. 2010;92(5):1080-8.
Atherton, P. J., Etheridge, T., Watt, P. W., Wilkinson, D., Selby, A., Rankin, D., Smith, K., & Rennie, M. J. (2010). Muscle full effect after oral protein: time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling. The American Journal of Clinical Nutrition, 92(5), 1080-8. https://doi.org/10.3945/ajcn.2010.29819
Atherton PJ, et al. Muscle Full Effect After Oral Protein: Time-dependent Concordance and Discordance Between Human Muscle Protein Synthesis and mTORC1 Signaling. Am J Clin Nutr. 2010;92(5):1080-8. PubMed PMID: 20844073.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Muscle full effect after oral protein: time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling. AU - Atherton,Philip J, AU - Etheridge,Timothy, AU - Watt,Peter W, AU - Wilkinson,Daniel, AU - Selby,Anna, AU - Rankin,Debbie, AU - Smith,Ken, AU - Rennie,Michael J, Y1 - 2010/09/15/ PY - 2010/9/17/entrez PY - 2010/9/17/pubmed PY - 2010/11/10/medline SP - 1080 EP - 8 JF - The American journal of clinical nutrition JO - Am J Clin Nutr VL - 92 IS - 5 N2 - BACKGROUND: We previously showed that human muscle protein synthesis (MPS) increased during infusion of amino acids (AAs) and peaked at ≈120 min before returning to baseline rates, despite elevated plasma AA concentrations. OBJECTIVE: We tested whether a protein meal elicited a similar response and whether signaling responses that regulate messenger RNA translation matched MPS changes. DESIGN: Eight postabsorptive healthy men (≈21 y of age) were studied during 8.5 h of primed continuous infusion of [1,2-¹³C₂]leucine with intermittent quadriceps biopsies for determination of MPS and anabolic signaling. After 2.5 h, subjects consumed 48 g whey protein. RESULTS: At 45-90 min after oral protein bolus, mean (± SEM) myofibrillar protein synthesis increased from 0.03 ± 0.003% to 0.10 ± 0.01%/h; thereafter, myofibrillar protein synthesis returned to baseline rates even though plasma essential AA (EAA) concentrations remained elevated (+130% at 120 min, +80% at 180 min). The activity of protein kinase B (PKB) and phosphorylation of eukaryotic initiation factor 4G preceded the rise of MPS and increases in phosphorylation of ribosomal protein kinase S6 (S6K1), and 4E-binding protein 1 (4EBP1) was superimposable with MPS responses until 90 min. However, although MPS decreased thereafter, all signals, with the exception of PKB activity (which mirrored insulin responses), remained elevated, which echoed the slowly declining plasma EAA profile. The phosphorylation of eukaryotic initiation factor 2α increased only at 180 min. Thus, discordance existed between MPS and the mammalian target of rapamycin complex 1 (mTORC1) and signaling (ie, S6K1 and 4EBP1 phosphorylation). CONCLUSIONS: We confirm our previous findings that MPS responses to AAs are transient, even with oral protein bolus. However, changes in MPS only reflect elevated mTORC1 signaling during the upswing in MPS. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/20844073/Muscle_full_effect_after_oral_protein:_time_dependent_concordance_and_discordance_between_human_muscle_protein_synthesis_and_mTORC1_signaling_ L2 - https://academic.oup.com/ajcn/article-lookup/doi/10.3945/ajcn.2010.29819 DB - PRIME DP - Unbound Medicine ER -