title: Rapamycin does not affect post-absorptive protein metabolism in human skeletal muscle.
abstract: Administration of the mTORC1 inhibitor, rapamycin, to humans blocks the increase in skeletal muscle protein synthesis in response to resistance exercise or amino acid ingestion.
  
  
  OBJECTIVE
  To determine whether rapamycin administration influences basal post-absorptive protein synthesis or breakdown in human skeletal muscle.
  
  
  METHODS
  Six young (26±2 years) subjects were studied during two separate trials, in which each trial was divided into two consecutive 2 h basal periods. The trials were identical except during one trial a single oral dose (16 mg) of rapamycin was administered immediately prior to the second basal period. Muscle biopsies were obtained from the vastus lateralis at 0, 2, and 4 h to examine protein synthesis, mTORC1 signaling, and markers of autophagy (LC3B-I and LC3B-II protein) associated with each 2 h basal period.
  
  
  RESULTS
  During the Control trial, muscle protein synthesis, whole body protein breakdown (phenylalanine Ra), mTORC1 signaling, and markers of autophagy were similar between both basal periods (p>0.05). During the Rapamycin trial, these variables were similar to the Control trial (p>0.05) and were unaltered by rapamycin administration (p>0.05). Thus, post-absorptive muscle protein metabolism and mTORC1 signaling were not affected by rapamycin administration.
  
  
  CONCLUSIONS
  Short-term rapamycin administration may only impair protein synthesis in human skeletal muscle when combined with a stimulus such as resistance exercise or increased amino acid availability.
authors.affiliation: Department of Nutrition and Metabolism, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Dickinson
authors.forename: Micah J
authors.initials: MJ
authors.lastname: Drummond
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Fry
authors.forename: David M
authors.initials: DM
authors.lastname: Gundermann
authors.forename: Dillon K
authors.initials: DK
authors.lastname: Walker
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Timmerman
authors.forename: Elena
authors.initials: E
authors.lastname: Volpi
authors.forename: Blake B
authors.initials: BB
authors.lastname: Rasmussen
mesh_terms: D000042:Absorption; D000328:Adult; D001343:Autophagy / Q000187:drug effects; D001706:Biopsy; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007700:Kinetics; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases; D055815:Young Adult
chemical_list: D046912:Multiprotein Complexes; D009124:Muscle Proteins; D011506:Proteins; D010649:Phenylalanine; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus