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

• Published in: Metabolism, clinical and experimental Vol. 62; no. 1; pp. 144 - 151
• Main Authors: Dickinson, Jared M., Drummond, Micah J., Fry, Christopher S., Gundermann, David M., Walker, Dillon K., Timmerman, Kyle L., Volpi, Elena, Rasmussen, Blake B.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.01.2013; Elsevier
• Subjects: Absorption; Adult; Autophagy; Autophagy - drug effects; Biological and medical sciences; Biopsy; Cross-Over Studies; Endocrinology & Metabolism; Feeding. Feeding behavior; Female; FSR; Fundamental and applied biological sciences. Psychology; Humans; Immunoblotting; ingestion; Kinetics; Male; Mechanistic Target of Rapamycin Complex 1; mTOR; Multiprotein Complexes; muscle protein; Muscle Proteins - metabolism; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; muscles; phenylalanine; Phenylalanine - metabolism; Phosphorylation - drug effects; protein synthesis; Proteins - antagonists & inhibitors; Proteins - metabolism; Signal Transduction - drug effects; Sirolimus - pharmacology; skeletal muscle; strength training; TOR Serine-Threonine Kinases; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Young Adult; RAP; CON; FSR; mTOR; 4E-BP1; LC3; mTORC1; Autophagy; Ra; S6K1; eukaryotic initiation factor 4E binding protein 1; Rapamycin trial; microtubule-associated protein 1 light chain 3; rate of appearance; fractional synthesis rate; mammalian target of rapamycin complex 1; Control trial; ribosomal S6 kinase 1; Antineoplastic agent; Human; Sirolimus; Lactone; Striated muscle; Metabolism; Macrolide; Protein; Macrocycle; Antibiotic; Protein synthesis inhibitor; Immunosuppressive agent; Endocrinology
• ISSN: 0026-0495; 1532-8600; 1532-8600
• DOI: 10.1016/j.metabol.2012.07.003

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. To determine whether rapamycin administration influences basal post-absorptive protein synthesis or breakdown in human skeletal muscle. Six young (26±2 years) subjects were studied during two separate trials, in which each trial was divided into two consecutive 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 were obtained from the vastus lateralis at 0, 2, and 4h to examine protein synthesis, mTORC1 signaling, and markers of autophagy (LC3B-I and LC3B-II protein) associated with each 2h basal period. 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. 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.