Rapamycin does not prevent increases in myofibrillar or mitochondrial protein synthesis following endurance exercise

Andrew Philp, Simon Schenk, Joaquin Perez-Schindler, D. Lee Hamilton, Leigh Breen, Erin Laverone, Stewart Jeromson, Stuart M. Phillips, Keith Baar

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


The present study aimed to investigate the role of the mechanistic target of rapamycin complex 1 (mTORC1) in the regulation of myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis following endurance exercise. Forty-two female C57BL/6 mice performed 1 h of treadmill running (18 m min<sup>-1</sup>; 5° grade), 1 h after i.p. administration of rapamycin (1.5 mg·kg<sup>-1</sup>) or vehicle. To quantify skeletal muscle protein fractional synthesis rates, a flooding dose (50 mg·kg<sup>-1</sup>) of l-[ring-<sup>13</sup>C<inf>6</inf>]phenylalanine was administered via i.p. injection. Blood and gastrocnemius muscle were collected in non-exercised control mice, as well as at 0.5, 3 and 6 h after completing exercise (n = 4 per time point). Skeletal muscle MyoPS and MitoPS were determined by measuring isotope incorporation in their respective protein pools. Activation of the mTORC1-signalling cascade was measured via direct kinase activity assay and immunoblotting, whereas genes related to mitochondrial biogenesis were measured via a quantitative RT-PCR. MyoPS increased rapidly in the vehicle group post-exercise and remained elevated for 6 h, whereas this response was transiently blunted (30 min post-exercise) by rapamycin. By contrast, MitoPS was unaffected by rapamycin, and was increased over the entire post-exercise recovery period in both groups (P < 0.05). Despite rapid increases in both MyoPS and MitoPS, mTORC1 activation was suppressed in both groups post-exercise for the entire 6 h recovery period. Peroxisome proliferator activated receptor-γ coactivator-1α, pyruvate dehydrogenase kinase 4 and mitochondrial transcription factor A mRNA increased post-exercise (P < 0.05) and this response was augmented by rapamycin (P < 0.05). Collectively, these data suggest that endurance exercise stimulates MyoPS and MitoPS in skeletal muscle independently of mTORC1 activation. Journal compilation

Original languageEnglish (US)
Pages (from-to)4275-4284
Number of pages10
JournalJournal of Physiology
Issue number18
StatePublished - Sep 1 2015

ASJC Scopus subject areas

  • Physiology


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