title: Leucine does not affect mechanistic target of rapamycin complex 1 assembly but is required for maximal ribosomal protein s6 kinase 1 activity in human skeletal muscle following resistance exercise.
abstract: We examined how the stimulatory effect of leucine on the mechanistic target of rapamycin complex 1 (mTORC1) pathway is affected by the presence of the remaining essential amino acids (EAAs). Nine male subjects performed resistance exercise on 4 occasions and were randomly supplied EAAs with leucine, EAAs without leucine (EAA-Leu), leucine alone, or flavored water (placebo; control). Muscle biopsies were taken from the vastus lateralis before and 60 and 90 min after exercise. Biopsies were analyzed for protein phosphorylation, kinase activity, protein-protein interactions, amino acid concentrations, and tracer incorporation. Leucine alone stimulated ribosomal protein s6 kinase 1 (S6K1) phosphorylation ∼280% more than placebo and EAA-Leu after exercise. Moreover, this response was enhanced by 60-75% after intake of EAAs compared with that of leucine alone (P < 0.05). Kinase activity of S6K1 reflected that of S6K1 phosphorylation; 60 min after exercise, the activity was elevated 3.3- and 4.2-fold with intake of leucine alone and with EAAs, respectively (P < 0.05). The interaction between mammalian target of rapamycin and regulatory-associated protein of mammalian target of rapamycin was unaltered in response to both resistance exercise and amino acid provision. Leucine alone stimulates mTORC1 signaling, although this response is enhanced by other EAAs and does not appear to be caused by alterations in mTORC1 assembly.
authors.affiliation: *Åstrand Laboratory, Swedish School of Sport and Health Sciences, Stockholm, Sweden; Department of Clinical Science, Intervention, and Technology, and Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Health and Exercise Sciences Research Group, University of Stirling, Stirling, United Kingdom; and Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden william.apro@gih.se.
authors.forename: William
authors.initials: W
authors.lastname: Apró
authors.affiliation: *Åstrand Laboratory, Swedish School of Sport and Health Sciences, Stockholm, Sweden; Department of Clinical Science, Intervention, and Technology, and Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Health and Exercise Sciences Research Group, University of Stirling, Stirling, United Kingdom; and Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Moberg
authors.affiliation: *Åstrand Laboratory, Swedish School of Sport and Health Sciences, Stockholm, Sweden; Department of Clinical Science, Intervention, and Technology, and Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Health and Exercise Sciences Research Group, University of Stirling, Stirling, United Kingdom; and Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden.
authors.forename: D Lee
authors.initials: DL
authors.lastname: Hamilton
authors.affiliation: *Åstrand Laboratory, Swedish School of Sport and Health Sciences, Stockholm, Sweden; Department of Clinical Science, Intervention, and Technology, and Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Health and Exercise Sciences Research Group, University of Stirling, Stirling, United Kingdom; and Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Ekblom
authors.affiliation: *Åstrand Laboratory, Swedish School of Sport and Health Sciences, Stockholm, Sweden; Department of Clinical Science, Intervention, and Technology, and Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Health and Exercise Sciences Research Group, University of Stirling, Stirling, United Kingdom; and Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden.
authors.forename: Olav
authors.initials: O
authors.lastname: Rooyackers
authors.affiliation: *Åstrand Laboratory, Swedish School of Sport and Health Sciences, Stockholm, Sweden; Department of Clinical Science, Intervention, and Technology, and Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Health and Exercise Sciences Research Group, University of Stirling, Stirling, United Kingdom; and Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden.
authors.forename: Hans-Christer
authors.initials: HC
authors.lastname: Holmberg
authors.affiliation: *Åstrand Laboratory, Swedish School of Sport and Health Sciences, Stockholm, Sweden; Department of Clinical Science, Intervention, and Technology, and Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Health and Exercise Sciences Research Group, University of Stirling, Stirling, United Kingdom; and Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Blomstrand
mesh_terms: D000328:Adult; D000601:Amino Acids, Essential / Q000008:administration & dosage / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007930:Leucine / Q000494:pharmacology* / Q000600:supply & distribution; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000601:Amino Acids, Essential; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D007930:Leucine
keywords: S6K1 kinase activity; mTORC1 assembly; protein synthesis