title: The impact of delivery profile of essential amino acids upon skeletal muscle protein synthesis in older men: clinical efficacy of pulse vs. bolus supply.
abstract: Essential amino acids (EAA) are responsible for skeletal muscle anabolic effects after nutrient intake. The pattern of appearance of EAA in blood, e.g., after intake of "slow" or "fast" protein sources or in response to grazing vs. bolus feeding patterns, may impact anabolism. However, the influence of this on muscle anabolism is poorly understood, particularly in older individuals. We determined the effects of divergent feeding profiles of EAA on blood flow, anabolic signaling, and muscle protein synthesis (MPS) in older men. Sixteen men (∼70 yr) consumed EAA either as a single dose (bolus, 15 g; n = 8) or as small repeated fractions (pulse, 4 × 3.75 g every 45 min; n = 8) during (13)C6 phenylalanine infusion. Repeated blood samples and muscle biopsies permitted measurement of fasting and postprandial plasma EAA, insulin, anabolic signaling, and MPS. Muscle blood flow was assessed by contrast-enhanced ultrasound (Sonovue). Bolus achieved rapid insulinemia (12.7 μiU/ml 25-min postfeed), essential aminoacidemia (∼3,000 μM, 45-65 min postfeed), and mTORC1 activity; pulse achieved attenuated insulin responses, gradual low-amplitude aminoacidemia (∼1,800 μM 80-195 min after feeding), and undetectable mTORC1 signaling. Despite this, equivalent anabolic responses were observed: fasting FSRs of 0.051 and 0.047%/h (bolus and pulse, respectively) increased to 0.084 and 0.073%/h, respectively. Moreover, pulse led to sustainment of MPS beyond 180 min, when bolus MPS had returned to basal rates. We detected no benefit of rapid aminoacidemia in this older population despite enhanced anabolic signaling and greater overall EAA exposure. Rather, apparent delayed onset of the "muscle-full" effect permitted identical MPS following low-amplitude-sustained EAA exposure.
authors.affiliation: Department of Clinical, Metabolic, and Molecular Physiology, MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, United Kingdom.
authors.forename: W Kyle
authors.initials: WK
authors.lastname: Mitchell
authors.affiliation: Department of Clinical, Metabolic, and Molecular Physiology, MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, United Kingdom.
authors.forename: Bethan E
authors.initials: BE
authors.lastname: Phillips
authors.affiliation: Department of Clinical, Metabolic, and Molecular Physiology, MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, United Kingdom.
authors.forename: John P
authors.initials: JP
authors.lastname: Williams
authors.affiliation: Department of Clinical, Metabolic, and Molecular Physiology, MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, United Kingdom.
authors.forename: Debbie
authors.initials: D
authors.lastname: Rankin
authors.affiliation: Department of Clinical, Metabolic, and Molecular Physiology, MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, United Kingdom.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Lund
authors.affiliation: Department of Clinical, Metabolic, and Molecular Physiology, MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, United Kingdom.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wilkinson
authors.affiliation: Department of Clinical, Metabolic, and Molecular Physiology, MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, United Kingdom.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Smith
authors.affiliation: Department of Clinical, Metabolic, and Molecular Physiology, MRC-ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Derby, United Kingdom philip.atherton@nottingham.ac.uk.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Atherton
mesh_terms: D000368:Aged; D000601:Amino Acids, Essential / Q000008:administration & dosage* / Q000378:metabolism; D002247:Carbon Isotopes / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D010649:Phenylalanine / Q000008:administration & dosage* / Q000378:metabolism; D014176:Protein Biosynthesis; D052097:Quadriceps Muscle / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism*; D012039:Regional Blood Flow; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014463:Ultrasonography
chemical_list: D000601:Amino Acids, Essential; D002247:Carbon Isotopes; D007328:Insulin; D046912:Multiprotein Complexes; D009124:Muscle Proteins; D010649:Phenylalanine; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: amino acids; anabolic signaling; muscle full state; nutrition; protein synthesis; skeletal muscle