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Rapamycin administration does not impair basal protein metabolism in human skeletal muscle
Author(s) -
Dickinson Jared M,
Drummond Micah J,
Fry Christopher S,
Gundermann David M,
Walker Dillon K,
Volpi Elena,
Rasmussen Blake B
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1075.3
Subject(s) - mtorc1 , skeletal muscle , autophagy , basal (medicine) , endocrinology , medicine , biology , pharmacology , signal transduction , pi3k/akt/mtor pathway , biochemistry , insulin , apoptosis
We have previously shown that administration of the mTORC1 inhibitor, rapamycin, to humans blocks the increase in skeletal muscle protein synthesis (MPS) in response to resistance exercise and amino acid ingestion. Whether rapamycin administration impairs basal MPS in human skeletal muscle is unknown. Six young (26±2y) subjects were studied during two separate 4h trials, in which each trial was divided into two, 2h basal periods. The trials were identical except during one trial a single oral dose (16mg) of rapamycin was administered immediately prior to the second basal period. Muscle biopsies ( vastus lateralis ) were obtained at 0, 2 and 4h, marking the beginning and end of each basal period, to examine MPS, mTORC1 signaling, and markers of autophagy (LC3BI and LC3BII protein). During the control trial, MPS, 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, basal protein metabolism and mTORC1 signaling were not affected by rapamycin administration. We conclude that rapamycin administration only impairs mTORC1 signaling and MPS in human skeletal muscle when combined with a stimulus such as resistance exercise or increased amino acid availability. NIAMS R01AR049877, NIA P30AG024832, NIH T32HD07539, NCRR 1UL1RR029876