title: Activation of mTORC1 signaling and protein synthesis in human muscle following blood flow restriction exercise is inhibited by rapamycin.
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 h postexercise. 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 whether mTORC1 signaling is necessary for stimulating muscle protein synthesis after BFR exercise. A secondary aim was to describe the 24-h 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 (CON) and rapamycin (RAP) groups completed BFR exercise; however, RAP was administered 16 mg of the mTOR inhibitor rapamycin 1 h prior to BFR exercise. BFR exercise consisted of four sets of leg extension exercise at 20% of 1 RM. Muscle biopsies were collected from the vastus lateralis before exercise and at 3, 6, and 24 h after BFR exercise. Mixed-muscle protein fractional synthetic rate increased by 42% at 3 h postexercise and 69% at 24 h postexercise in CON, whereas this increase was inhibited in the RAP group. Phosphorylation of mTOR (Ser(2448)) and S6K1 (Thr(389)) was 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.
authors.affiliation: Department of Nutrition and Metabolism, Division of Rehabilitation Sciences.
authors.forename: David M
authors.initials: DM
authors.lastname: Gundermann
authors.affiliation: Department of Nutrition and Metabolism, Division of Rehabilitation Sciences.
authors.forename: Dillon K
authors.initials: DK
authors.lastname: Walker
authors.affiliation: Department of Nutrition and Metabolism, Division of Rehabilitation Sciences.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Reidy
authors.affiliation: Department of Nutrition and Metabolism, Division of Rehabilitation Sciences.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Borack
authors.affiliation: Department of Nutrition and Metabolism, Division of Rehabilitation Sciences, Sealy Center on Aging, and.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Dickinson
authors.affiliation: Division of Rehabilitation Sciences, Sealy Center on Aging, and Department of Internal Medicine-Geriatrics, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Elena
authors.initials: E
authors.lastname: Volpi
authors.affiliation: Department of Nutrition and Metabolism, Division of Rehabilitation Sciences, Sealy Center on Aging, and blrasmus@utmb.edu.
authors.forename: Blake B
authors.initials: BB
authors.lastname: Rasmussen
mesh_terms: D000293:Adolescent; D000328:Adult; D003250:Constriction; D015444:Exercise / Q000502:physiology*; D006801:Humans; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D012039:Regional Blood Flow / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000008:administration & dosage*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D046912:Multiprotein Complexes; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: blood flow restriction exercise; fractional synthetic rate; mammalian target of rapamycin; mammalian target of rapamycin complex 1; rapamycin