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.
Materials/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.
Abbreviations:
CON (Control trial), 4E-BP1 (eukaryotic initiation factor 4E binding protein 1), FSR (fractional synthesis rate), LC3 (microtubule-associated protein 1 light chain 3), mTORC1 (mammalian target of rapamycin complex 1), Ra (rate of appearance), RAP (Rapamycin trial), S6K1 (ribosomal S6 kinase 1.)Keywords
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Article info
Publication history
Published online: September 10, 2012
Accepted:
July 11,
2012
Received:
February 23,
2012
Footnotes
This trial was registered at clinicaltrials.gov as NCT00891696.
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
