Rapamycin does not affect post-absorptive protein metabolism in human skeletal muscle

Jared M. Dickinson, Micah J. Drummond, Christopher Fry, David M. Gundermann, Dillon K. Walker, Kyle L. Timmerman, Elena Volpi, Blake Rasmussen

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)144-151
Number of pages8
JournalMetabolism: Clinical and Experimental
Volume62
Issue number1
DOIs
StatePublished - Jan 2013

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Sirolimus
Skeletal Muscle
Muscle Proteins
Proteins
Autophagy
Amino Acids
Quadriceps Muscle
Phenylalanine
Eating
Biopsy
Muscles
mechanistic target of rapamycin complex 1

Keywords

  • Autophagy
  • FSR
  • mTOR

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Rapamycin does not affect post-absorptive protein metabolism in human skeletal muscle. / Dickinson, Jared M.; Drummond, Micah J.; Fry, Christopher; Gundermann, David M.; Walker, Dillon K.; Timmerman, Kyle L.; Volpi, Elena; Rasmussen, Blake.

In: Metabolism: Clinical and Experimental, Vol. 62, No. 1, 01.2013, p. 144-151.

Research output: Contribution to journalArticle

Dickinson, Jared M. ; Drummond, Micah J. ; Fry, Christopher ; Gundermann, David M. ; Walker, Dillon K. ; Timmerman, Kyle L. ; Volpi, Elena ; Rasmussen, Blake. / Rapamycin does not affect post-absorptive protein metabolism in human skeletal muscle. In: Metabolism: Clinical and Experimental. 2013 ; Vol. 62, No. 1. pp. 144-151.
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