Skeletal muscle Ras-related GTP binding B mRNA and protein expression is increased after essential amino acid ingestion in healthy humans

J Nutr. 2014 Sep;144(9):1409-14. doi: 10.3945/jn.114.196691. Epub 2014 Jul 23.

Abstract

Essential amino acids (EAAs) are potent stimulators of mechanistic target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis. However, regulators upstream of mTORC1 that are responsive to EAA availability are not well described, especially in human skeletal muscle. The purpose of this study was to determine changes in leucyl-tRNA synthetase (LARS/LARS) and Ras-related GTP binding B (RAGB/RAGB) mRNA and protein expression in healthy human skeletal muscle after acute EAA ingestion. Muscle biopsies sampled from the vastus lateralis were obtained from 13 young adults (7 males, 6 females; aged 22.9 ± 0.9 y; body mass index 21.7 ± 0.9 kg/m(2)) in the fasting state (baseline) and 1 and 3 h after EAA (13 g; 2.4 g of Leu) ingestion. Real-time quantitative polymerase chain reaction and Western blotting were used to determine changes in LARS/LARS and RAGB/RAGB mRNA and protein expression, respectively. Stable isotope tracers and gas chromatography mass spectrometry were used to determine Leu intracellular concentrations and muscle protein synthesis. EAA ingestion increased RAGB/RAGB mRNA (∼60%) and protein (∼100%) abundance in adult skeletal muscle (P ≤ 0.05). EAAs also increased muscle Leu concentrations (∼130%), mTOR phosphorylation (∼30%), and muscle protein synthesis (∼50%; P ≤ 0.05) but did not alter muscle LARS/LARS abundance (P > 0.05). We conclude that acute EAA ingestion is capable of increasing RAGB expression in human skeletal muscle. Future work is needed to determine whether this adaptive response is important to promote muscle protein anabolism in humans. This trial was registered at clinicaltrials.gov as NCT01669590.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Amino Acids, Essential / metabolism*
  • Female
  • Guanosine Triphosphate / metabolism*
  • Humans
  • Leucine / metabolism
  • Leucine-tRNA Ligase / genetics
  • Leucine-tRNA Ligase / metabolism*
  • Male
  • Mechanistic Target of Rapamycin Complex 1
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism*
  • Multiprotein Complexes / metabolism
  • Muscle Proteins / metabolism*
  • Phosphorylation
  • Protein Biosynthesis*
  • Protein Processing, Post-Translational
  • Quadriceps Muscle / metabolism*
  • RNA, Messenger / metabolism
  • Reference Values
  • TOR Serine-Threonine Kinases / metabolism
  • Young Adult

Substances

  • Amino Acids, Essential
  • Multiprotein Complexes
  • Muscle Proteins
  • RNA, Messenger
  • Guanosine Triphosphate
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1
  • Monomeric GTP-Binding Proteins
  • Leucine-tRNA Ligase
  • Leucine

Associated data

  • ClinicalTrials.gov/NCT01669590