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Activation of mTORC1 Signaling and Protein Synthesis in Human Muscle Following Blood Flow Restriction Exercise is Inhibited by Rapamycin

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AJP Endocrinology and Metabolism

Published online on

Abstract

Restriction of blood flow to a contracting muscle during low-intensity resistance exercise (BFR exercise) stimulates mTORC1 signaling and protein synthesis in human muscle within 3 hours post-exercise. However, there is a lack of mechanistic data to provide a direct link between mTORC1 activation and protein synthesis in human skeletal muscle following BFR exercise. Therefore, the primary purpose of this study was to determine if mTORC1 signaling is necessary for stimulating muscle protein synthesis after BFR exercise. A secondary aim was to describe the 24-hour time-course response in muscle protein synthesis and breakdown following BFR exercise. Sixteen healthy young men were randomized to one of two groups. Both the control group (CON) and rapamycin (RAP) groups completed BFR exercise however, RAP was administered 16mg of the mTOR inhibitor, rapamycin, one hour prior to BFR exercise. BFR exercise consisted of 4 sets of leg extension exercise at 20% of 1RM. Muscle biopsies were collected from the vastus lateralis before exercise and at 3, 6 and 24 hr after BFR exercise. Mixed muscle protein fractional synthetic rate increased by 42% at 3 hr post-exercise and 69% at 24 hr post-exercise in CON whereas this increase was inhibited in the RAP group. Phosphorylation of mTOR (Ser2448) and S6K1 (Thr389) were also increased in CON but inhibited in RAP. Mixed muscle protein breakdown was not significantly different across time or groups. We conclude that activation of mTORC1 signaling and protein synthesis in human muscle following BFR exercise is inhibited in the presence of rapamycin.