Activation of mTORC1 signaling and protein synthesis in human muscle following blood flow restriction exercise is inhibited by rapamycin

David M. Gundermann, Dillon K. Walker, Paul T. Reidy, Michael S. Borack, Jared M. Dickinson, Elena Volpi, Blake Rasmussen

Research output: Contribution to journalArticle

40 Citations (Scopus)

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 (Ser2448 and S6K1 (Thr389 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume306
Issue number10
DOIs
StatePublished - May 15 2014

Fingerprint

Sirolimus
Exercise
Muscles
Proteins
Muscle Proteins
mechanistic target of rapamycin complex 1
Quadriceps Muscle
Leg
Skeletal Muscle
Phosphorylation
Biopsy

Keywords

  • Blood flow restriction exercise
  • Fractional synthetic rate
  • Mammalian target of rapamycin
  • Mammalian target of rapamycin complex 1
  • Rapamycin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

Activation of mTORC1 signaling and protein synthesis in human muscle following blood flow restriction exercise is inhibited by rapamycin. / Gundermann, David M.; Walker, Dillon K.; Reidy, Paul T.; Borack, Michael S.; Dickinson, Jared M.; Volpi, Elena; Rasmussen, Blake.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 306, No. 10, 15.05.2014.

Research output: Contribution to journalArticle

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