Excess leucine intake enhances muscle anabolic signaling but not net protein anabolism in young men and women

J Nutr. 2010 Nov;140(11):1970-6. doi: 10.3945/jn.110.127647. Epub 2010 Sep 15.

Abstract

Essential amino acids (EAA) stimulate skeletal muscle protein synthesis (MPS) in humans. Leucine may have a greater stimulatory effect on MPS than other EAA and/or decrease muscle protein breakdown (MPB). To determine the effect of 2 different leucine concentrations on muscle protein turnover and associated signaling, young men (n = 6) and women (n = 8) ingested 10 g EAA in 1 of 2 groups: composition typical of high quality proteins (CTRL; 1.8 g leucine) or increased leucine concentration (LEU; 3.5 g leucine). Participants were studied for 180 min postingestion. Fractional synthetic rate and leg phenylalanine and leucine kinetics were assessed on muscle biopsies using stable isotopic techniques. Signaling was determined by immunoblotting. Arterial leucine concentration and delivery to the leg increased in both groups and was significantly higher in LEU than in CTRL; however, transport into the muscle and intracellular availability did not differ between groups. MPS increased similarly in both groups 60 min postingestion. MPB decreased at 60 min only in LEU, but net muscle protein balance improved similarly. Components of mammalian target of rapamycin (mTOR) signaling were improved in LEU, but no changes were observed in ubiquitin-proteasome system signaling. Changes in light chain 3 and mTOR association with Unc-51-like kinase 1 indicate autophagy decreased more in LEU. We conclude that in 10 g of EAA, the leucine content typical of high quality proteins (~1.8 g) is sufficient to induce a maximal skeletal muscle protein anabolic response in young adults, but leucine may play a role in autophagy regulation.

Publication types

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

MeSH terms

  • Adult
  • Autophagy
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Biopsy
  • Carbon Isotopes
  • Female
  • Humans
  • Infusions, Intravenous
  • Kinetics
  • Leucine / administration & dosage*
  • Leucine / blood
  • Leucine / metabolism
  • Male
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / metabolism*
  • Phenylalanine / administration & dosage
  • Phenylalanine / metabolism
  • Proteasome Endopeptidase Complex / metabolism
  • Proteins
  • Quadriceps Muscle / blood supply
  • Quadriceps Muscle / metabolism
  • Regional Blood Flow
  • Signal Transduction*
  • TOR Serine-Threonine Kinases
  • Transcription Factors / metabolism
  • Ubiquitin / metabolism

Substances

  • Biomarkers
  • Carbon Isotopes
  • Multiprotein Complexes
  • Muscle Proteins
  • Proteins
  • Transcription Factors
  • Ubiquitin
  • Phenylalanine
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1
  • Proteasome Endopeptidase Complex
  • Leucine