An increase in essential amino acid availability upregulates amino acid transporter expression in human skeletal muscle

Micah J. Drummond, Erin L. Glynn, Christopher Fry, Kyle L. Timmerman, Elena Volpi, Blake Rasmussen

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Essential amino acids (EAA) stimulate skeletal muscle mammalian target of rapamycin complex 1 (mTORC1) signaling and protein synthesis. It has recently been reported that an increase in amino acid (AA) transporter expression during anabolic conditions is rapamycin-sensitive. The purpose of this study was to determine whether an increase in EAA availability increases AA transporter expression in human skeletal muscle. Muscle biopsies were obtained from the vastus lateralis of seven young adult subjects (3 male, 4 female) before and 1-3 h after EAA ingestion (10 g). Blood and muscle samples were analyzed for leucine kinetics using stable isotopic techniques. Quantitative RT-PCR, and immunoblotting were used to determine the mRNA and protein expression, respectively, of AA transporters and members of the general AA control pathway [general control nonrepressed (GCN2), activating transcription factor (ATF4), and eukaryotic initiation factor (eIF2) α-subunit (Ser52)]. EAA ingestion increased blood leucine concentration, delivery of leucine to muscle, transport of leucine from blood into muscle, intracellular muscle leucine concentration, ribosomal protein S6 (Ser240/244) phosphorylation, and muscle protein synthesis. This was followed with increased L-type AA transporter (LAT1), CD98, sodium-coupled neutral AA transporter (SNAT2), and proton-coupled amino acid transporter (PAT1) mRNA expression at 1 h (P < 0.05) and modest increases in LAT1 protein expression (3 h post-EAA) and SNAT2 protein expression (2 and 3 h post-EAA, P < 0.05). Although there were no changes in GCN2 expression and eIF2α phosphorylation, ATF4 protein expression reached significance by 2 h post-EAA (P < 0.05). We conclude that an increase in EAA availability upregulates human skeletal muscle AA transporter expression, perhaps in an mTORC1-dependent manner, which may be an adaptive response necessary for improved AA intracellular delivery.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume298
Issue number5
DOIs
StatePublished - May 2010

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Amino Acid Transport Systems
Essential Amino Acids
Skeletal Muscle
Up-Regulation
Leucine
Muscles
Large Neutral Amino Acid-Transporter 1
Proteins
Neutral Amino Acid Transport Systems
Eating
Ribosomal Protein S6
Activating Transcription Factors
Phosphorylation
Eukaryotic Initiation Factors
Amino Acids
Messenger RNA
Muscle Proteins
Quadriceps Muscle
Sirolimus
Immunoblotting

Keywords

  • L-type amino acid transporter type 1
  • Mammalian target of rapamycin
  • Nutrient signaling
  • Protein metabolism
  • Sodium-coupled neutral amino acid transporter type 2

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

An increase in essential amino acid availability upregulates amino acid transporter expression in human skeletal muscle. / Drummond, Micah J.; Glynn, Erin L.; Fry, Christopher; Timmerman, Kyle L.; Volpi, Elena; Rasmussen, Blake.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 298, No. 5, 05.2010.

Research output: Contribution to journalArticle

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