title: Intake of branched-chain or essential amino acids attenuates the elevation in muscle levels of PGC-1α4 mRNA caused by resistance exercise.
abstract: The transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is recognized as the master regulator of mitochondrial biogenesis. However, recently a novel isoform, PGC-1α4, that specifically regulates muscle hypertrophy was discovered. Because stimulation of mechanistic target of rapamycin complex 1 (mTORC1) activity is tightly coupled to hypertrophy, we hypothesized that activation of this pathway would upregulate PGC-1α4. Eight male subjects performed heavy resistance exercise (10 × 8-12 repetitions at ∼75% of 1 repetition maximum in leg press) on four different occasions, ingesting in random order a solution containing essential amino acids (EAA), branched-chain amino acids (BCAA), leucine, or flavored water (placebo) during and after the exercise. Biopsies were taken from the vastus lateralis muscle before and immediately after exercise, as well as following 90 and 180 min of recovery. Signaling through mTORC1, as reflected in p70S6 kinase phosphorylation, was stimulated to a greater extent by the EAA and BCAA than the leucine or placebo supplements. Unexpectedly, intake of EAA or BCAA attenuated the stimulatory effect of exercise on PGC-1α4 expression by ∼50% (from a 10- to 5-fold increase with BCAA and EAA, P < 0.05) 3 h after exercise, whereas intake of leucine alone did not reduce this response. The 60% increase (P < 0.05) in the level of PGC-1α1 mRNA 90 min after exercise was uninfluenced by amino acid intake. Muscle glycogen levels were reduced and AMP-activated protein kinase α2 activity and phosphorylation of p38 mitogen-activated protein kinase enhanced to the same extent with all four supplements. In conclusion, induction of PGC-1α4 does not appear to regulate the nutritional (BCAA or EAA)-mediated activation of mTORC1 in human muscle.
authors.affiliation: The Åstrand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden; and.
authors.forename: Hedvig
authors.initials: H
authors.lastname: Samuelsson
authors.affiliation: The Åstrand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden; and.
authors.forename: Marcus
authors.initials: M
authors.lastname: Moberg
authors.affiliation: The Åstrand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden; and.
authors.forename: William
authors.initials: W
authors.lastname: Apró
authors.affiliation: The Åstrand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden; and.
authors.forename: Björn
authors.initials: B
authors.lastname: Ekblom
authors.affiliation: The Åstrand Laboratory, The Swedish School of Sport and Health Sciences, Stockholm, Sweden; and Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden eva.blomstrand@gih.se.
authors.forename: Eva
authors.initials: E
authors.lastname: Blomstrand
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D000597:Amino Acids, Branched-Chain / Q000494:pharmacology*; D000601:Amino Acids, Essential / Q000494:pharmacology*; D015444:Exercise; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007930:Leucine / Q000494:pharmacology*; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000187:drug effects* / Q000235:genetics; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics; D052097:Quadriceps Muscle / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D055070:Resistance Training; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
chemical_list: D000597:Amino Acids, Branched-Chain; D000601:Amino Acids, Essential; D046912:Multiprotein Complexes; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020033:Protein Isoforms; D012333:RNA, Messenger; D006003:Glycogen; D000076222:Mechanistic Target of Rapamycin Complex 1; C526181:PRKAA2 protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D007930:Leucine
keywords: mechanistic target of rapamycin; mitochondrial biogenesis; peroxisome proliferator-activated receptor-γ coactivator-1α isoforms; skeletal muscle