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

Citation

Philp A, Schenk S, Perez-Schindler J, Hamilton DL, Breen L, Laverone E, Jeromson S, Phillips SM & Baar K (2015) Rapamycin does not prevent increases in myofibrillar or mitochondrial protein synthesis following endurance exercise. Journal of Physiology, 593 (18), pp. 4275-4284. https://doi.org/10.1113/JP271219

Abstract
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 1h of treadmill running (18mmin−1; 5° grade), 1h afteri.p.administration of rapamycin (1.5mg · kg−1) or vehicle. To quantify skeletal muscle protein fractional synthesis rates, a flooding dose (50mg · kg−1) ofl-[ring-13C6]phenylalanine was administered viai.p.injection. Blood and gastrocnemius muscle were collected in non-exercised control mice, as well as at 0.5, 3 and 6h 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 6h, whereas this response was transiently blunted (30min 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 6h 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
Journal of Physiology: Volume 593, Issue 18