Protein-leucine ingestion activates a regenerative inflammo-myogenic transcriptome in skeletal muscle following intense endurance exercise.
Protein-leucine supplement ingestion following strenuous endurance exercise accentuates skeletal-muscle protein synthesis and adaptive molecular responses, but the underlying transcriptome is uncharacterized. In a randomized single-blind triple-crossover design, 12 trained men completed 100 min of high-intensity cycling then ingested 70/15/180/30 g protein-leucine-carbohydrate-fat (15LEU), 23/5/180/30 g (5LEU), or 0/0/274/30 g (CON) beverages during the first 90 min of a 240 min recovery period. Vastus lateralis muscle samples (30 and 240 min postexercise) underwent transcriptome analysis by microarray followed by bioinformatic analysis. Gene expression was regulated by protein-leucine in a dose-dependent manner affecting the inflammatory response and muscle growth and development. At 30 min, 15LEU and 5LEU vs. CON activated transcriptome networks with gene-set functions involving cell-cycle arrest (Z-score 2.0-2.7, P < 0.01), leukocyte maturation (1.7, P = 0.007), cell viability (2.4, P = 0.005), promyogenic networks encompassing myocyte differentiation and myogenin (MYOD1, MYOG), and a proteinaceous extracellular matrix, adhesion, and development program correlated with plasma lysine, arginine, tyrosine, taurine, glutamic acid, and asparagine concentrations. High protein-leucine dose (15LEU-5LEU) activated an IL-1I-centered proinflammatory network and leukocyte migration, differentiation, and survival functions (2.0-2.6, <0.001). By 240 min, the protein-leucine transcriptome was anti-inflammatory and promyogenic (IL-6, NF- β, SMAD, STAT3 network inhibition), with overrepresented functions including decreased leukocyte migration and connective tissue development (-1.8-2.4, P < 0.01), increased apoptosis of myeloid and muscle cells (2.2-3.0, P < 0.002), and cell metabolism (2.0-2.4, P < 0.01). The analysis suggests protein-leucine ingestion modulates inflammatory-myogenic regenerative processes during skeletal muscle recovery from endurance exercise. Further cellular and translational research is warranted to validate amino acid-mediated myeloid and myocellular mechanisms within skeletal-muscle functional plasticity.
School of Sport and Exercise and Institute of Food Nutrition, and Human Health, Massey University, Wellington, New Zealand; and D.S.Rowlands@massey.ac.nz.
David S
DS
Rowlands
School of Sport and Exercise and Institute of Food Nutrition, and Human Health, Massey University, Wellington, New Zealand; and Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, Australia;
Andre R
AR
Nelson
Nestle Research Centre, Lausanne, Switzerland; and Nestlé Institute of Health Sciences, Lausanne, Switzerland;
Frederic
F
Raymond
Nestle Research Centre, Lausanne, Switzerland; and Nestlé Institute of Health Sciences, Lausanne, Switzerland;
Sylviane
S
Metairon
Nestlé Institute of Health Sciences, Lausanne, Switzerland;
Robert
R
Mansourian
School of Sport and Exercise and Institute of Food Nutrition, and Human Health, Massey University, Wellington, New Zealand; and.
Jim
J
Clarke
Nestle Research Centre, Lausanne, Switzerland; and Canadian Sport Institute Pacific, Victoria, Canada; and.
Trent
T
Stellingwerff
McMaster University, Department of Kinesiology, Hamilton, Canada.
Stuart M
SM
Phillips
D000328:Adult; D015444:Exercise; D053263:Gene Regulatory Networks; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007930:Leucine / Q000008:administration & dosage*; D008297:Male; D008954:Models, Biological; D005810:Multigene Family; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010807:Physical Endurance; D015203:Reproducibility of Results; D012984:Software; D059467:Transcriptome / Q000235:genetics*
D007930:Leucine
inflammation; macrophage; microarray; myogenesis; regeneration; satellite cells