Activation of mTORC1 by leucine is potentiated by branched-chain amino acids and even more so by essential amino acids following resistance exercise

Am J Physiol Cell Physiol. 2016 Jun 1;310(11):C874-84. doi: 10.1152/ajpcell.00374.2015. Epub 2016 Apr 6.


Protein synthesis is stimulated by resistance exercise and intake of amino acids, in particular leucine. Moreover, activation of mammalian target of rapamycin complex 1 (mTORC1) signaling by leucine is potentiated by the presence of other essential amino acids (EAA). However, the contribution of the branched-chain amino acids (BCAA) to this effect is yet unknown. Here we compare the stimulatory role of leucine, BCAA, and EAA ingestion on anabolic signaling following exercise. Accordingly, eight trained volunteers completed four sessions of resistance exercise during which they ingested either placebo, leucine, BCAA, or EAA (including the BCAA) in random order. Muscle biopsies were taken at rest, immediately after exercise, and following 90 and 180 min of recovery. Following 90 min of recovery the activity of S6 kinase 1 (S6K1) was greater than at rest in all four trials (Placebo<Leucine<BCAA<EAA; P < 0.05 time × supplement), with a ninefold increase in the EAA trial. At this same time point, phosphorylation of eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) at Thr(37/46) was unaffected by supplementation, while that of Thr(46) alone exhibited a pattern similar to that of S6K1, being 18% higher with EAA than BCAA. However, after 180 min of recovery this difference between EAA and BCAA had disappeared, although with both these supplements the increases were still higher than with leucine (40%, P < 0.05) and placebo (100%, P < 0.05). In summary, EAA ingestion appears to stimulate translation initiation more effectively than the other supplements, although the results also suggest that this effect is primarily attributable to the BCAA.

Keywords: 4E-BP1; BCAA; S6K1; skeletal muscle.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Amino Acids, Branched-Chain / administration & dosage*
  • Amino Acids, Essential / administration & dosage*
  • Biopsy
  • Blood Glucose / metabolism
  • Cell Cycle Proteins
  • Energy Metabolism / drug effects
  • Eukaryotic Initiation Factor-4E / metabolism
  • Healthy Volunteers
  • Humans
  • Insulin / blood
  • Lactic Acid / blood
  • Leucine / administration & dosage*
  • Male
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes / agonists*
  • Multiprotein Complexes / metabolism
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / enzymology
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Biosynthesis / drug effects
  • Resistance Training*
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism
  • Time Factors
  • Treatment Outcome


  • Adaptor Proteins, Signal Transducing
  • Amino Acids, Branched-Chain
  • Amino Acids, Essential
  • Blood Glucose
  • Cell Cycle Proteins
  • EIF4EBP1 protein, human
  • Eukaryotic Initiation Factor-4E
  • Insulin
  • Multiprotein Complexes
  • Phosphoproteins
  • Lactic Acid
  • Mechanistic Target of Rapamycin Complex 1
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • ribosomal protein S6 kinase, 70kD, polypeptide 1
  • Leucine