title: A dose- rather than delivery profile-dependent mechanism regulates the "muscle-full" effect in response to oral essential amino acid intake in young men.
abstract: BACKGROUND
  The anabolic response of skeletal muscle to essential amino acids (EAAs) is dose dependent, maximal at modest doses, and short lived, even with continued EAA availability, a phenomenon termed "muscle-full." However, the effect of EAA ingestion profile on muscle metabolism remains undefined.
  
  
  OBJECTIVE
  We determined the effect of Bolus vs. Spread EAA feeding in young men and hypothesized that muscle-full is regulated by a dose-, not delivery profile-, dependent mechanism.
  
  
  METHODS
  We provided 16 young healthy men with 15 g mixed-EAA, either as a single dose ("Bolus"; n = 8) or in 4 fractions at 45-min intervals ("Spread"; n = 8). Plasma insulin and EAA concentrations were assayed by ELISA and ion-exchange chromatography, respectively. Limb blood flow by was determined by Doppler ultrasound, muscle microvascular flow by Sonovue (Bracco) contrast-enhanced ultrasound, and phosphorylation of mammalian target of rapamycin complex 1 substrates by immunoblotting. Intermittent muscle biopsies were taken to quantify myofibrillar-bound (13)C6-phenylalanine to determine muscle protein synthesis (MPS).
  
  
  RESULTS
  Bolus feeding achieved rapid insulinemia (13.6 μIU · mL(-1), 25 min after commencement of feeding), aminoacidemia (∼2500 μM at 45 min), and capillary recruitment (+45% at 45 min), whereas Spread feeding achieved attenuated insulin responses, gradual low-amplitude aminoacidemia (peak: ∼1500 μM at 135 min), and no detectable capillary recruitment (all P < 0.01 vs. Bolus). Despite these differences, identical anabolic responses were observed; fasting fractional synthetic rates of 0.054% · h(-1) (Bolus) and 0.066% · h(-1) (Spread) increased to 0.095% and 0.104% · h(-1) (no difference in increment or final values between regimens). With both Spread and Bolus feeding strategies, a latency of at least 90 min was observed before an upswing in MPS was evident. Similarly with both feeding strategies, MPS returned to fasting rates by 180 min despite elevated circulating EAAs.
  
  
  CONCLUSIONS
  These data do not support EAA delivery profile as an important determinant of anabolism in young men at rest, nor rapid aminoacidemia/leucinemia as being a key factor in maximizing MPS. This trial was registered at clinicaltrials.gov as NCT01735539.
authors: Clinical, Metabolic, and Molecular Physiology, MRC-Arthritis Research UK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, United Kingdom; and Departments of Surgery and.
authors: William Kyle
authors: WK
authors: Mitchell
authors: Clinical, Metabolic, and Molecular Physiology, MRC-Arthritis Research UK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, United Kingdom; and.
authors: Beth E
authors: BE
authors: Phillips
authors: Clinical, Metabolic, and Molecular Physiology, MRC-Arthritis Research UK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, United Kingdom; and Anaesthesia, Royal Derby Hospital, Derby, United Kingdom.
authors: John P
authors: JP
authors: Williams
authors: Clinical, Metabolic, and Molecular Physiology, MRC-Arthritis Research UK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, United Kingdom; and.
authors: Debbie
authors: D
authors: Rankin
authors: Clinical, Metabolic, and Molecular Physiology, MRC-Arthritis Research UK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, United Kingdom; and Departments of Surgery and.
authors: Jonathan N
authors: JN
authors: Lund
authors: Clinical, Metabolic, and Molecular Physiology, MRC-Arthritis Research UK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, United Kingdom; and.
authors: Kenneth
authors: K
authors: Smith
authors: Clinical, Metabolic, and Molecular Physiology, MRC-Arthritis Research UK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, United Kingdom; and philip.atherton@nottingham.ac.uk.
authors: Philip J
authors: PJ
authors: Atherton
mesh_terms: D000284:Administration, Oral; D000601:Amino Acids, Essential / Q000008:administration & dosage* / Q000097:blood; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000502:physiology*; D010649:Phenylalanine / Q000097:blood; D010766:Phosphorylation; D014176:Protein Biosynthesis; D055815:Young Adult
chemical_list: D000601:Amino Acids, Essential; D007328:Insulin; D009124:Muscle Proteins; D010649:Phenylalanine
keywords: anabolic signaling; blood flow; essential amino acids; muscle protein synthesis; muscle-full; nutrition; skeletal muscle
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