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. doi: 10.3945/ajcn.2010.29819. Epub 2010 Sep 15.

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.

Publication types

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

MeSH terms

  • Adult
  • Amino Acids / blood*
  • Dietary Proteins / administration & dosage*
  • Eukaryotic Initiation Factors / metabolism
  • Humans
  • Male
  • Mechanistic Target of Rapamycin Complex 1
  • Milk Proteins / pharmacology*
  • Multiprotein Complexes
  • Muscle Proteins / biosynthesis*
  • Phosphorylation
  • Proteins
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quadriceps Muscle / metabolism*
  • Ribosomal Protein S6 Kinases / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases
  • Time Factors
  • Transcription Factors / metabolism*
  • Whey Proteins
  • Young Adult

Substances

  • Amino Acids
  • Dietary Proteins
  • Eukaryotic Initiation Factors
  • Milk Proteins
  • Multiprotein Complexes
  • Muscle Proteins
  • Proteins
  • Transcription Factors
  • Whey Proteins
  • Mechanistic Target of Rapamycin Complex 1
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases
  • TOR Serine-Threonine Kinases