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

摘要

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⁻¹; 5° grade), 1 h after i.p. administration of rapamycin (1.5 mg · kg⁻¹) or vehicle. To quantify skeletal muscle protein fractional synthesis rates, a flooding dose (50 mg · kg⁻¹) of l-[ring-¹³C6]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.Key points class="unordered" style="list-style-type:disc"> Previous studies have shown that endurance exercise increases myofibrillar (MyoPS) and mitochondrial (MitoPS) protein synthesis in skeletal muscle. The mechanistic target of rapamycin (mTOR) is considered to be a key intracellular nutrient-sensing protein complex, which activates MyoPS in response to anabolic stimuli. Little is known regarding the regulation of MyoPS and MitoPS in response to endurance exercise. In the present study, we show that MyoPS and MitoPS increase in skeletal muscle following endurance exercise, despite suppression of mTORC1 during the post-exercise recovery period. Our data suggests that mTORC1 independent processes regulate both MyoPS and MitoPS following acute endurance exercise.