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

Unlabelled: 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.