Blood Flow Restriction Only Increases Myofibrillar Protein Synthesis with Exercise

Blood flow restriction (BFR) to contracting skeletal muscle during low-intensity resistance exercise training increases muscle strength and size in humans. However, the mechanism(s) underlying these effects are largely unknown. We have previously shown that mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis (MPS) are stimulated following an acute bout of BFR exercise. The purpose of this study was to test the hypothesis that reactive hyperemia is the mechanism responsible for stimulating mTORC1 signaling and MPS following BFR exercise. Six young men (24 ± 2 yr) were used in a randomized crossover study consisting of two exercise trials: low-intensity resistance exercise with BFR (BFR trial) and low-intensity resistance exercise with sodium nitroprusside (SNP), a pharmacological vasodilator infusion into the femoral artery immediately after exercise to simulate the reactive hyperemia response after BFR exercise (SNP trial). Postexercise mixed-muscle fractional synthetic rate from the vastus lateralis increased by 49% in the BFR trial ( P < 0.05) with no change in the SNP trial ( P > 0.05). BFR exercise increased the phosphorylation of mTOR, S6 kinase 1, ribosomal protein S6, ERK1/2, and Mnk1-interacting kinase 1 ( P < 0.05) with no changes in mTORC1 signaling in the SNP trial ( P > 0.05). We conclude that reactive hyperemia is not a primary mechanism for BFR exercise-induced mTORC1 signaling and MPS. Further research is necessary to elucidate the cellular mechanism(s) responsible for the increase in mTOR signaling, MPS, and hypertrophy following acute and chronic BFR exercise.

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Citrulline does not enhance blood flow, microvascular circulation, or myofibrillar protein synthesis in elderly men at rest or following exercise

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00096.2014 ◽

2014 ◽

Vol 307 (1) ◽

pp. E71-E83 ◽

Cited By ~ 36

Author(s):

Tyler A. Churchward-Venne ◽

Lisa M. Cotie ◽

Maureen J. MacDonald ◽

Cameron J. Mitchell ◽

Todd Prior ◽

...

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Blood Flow ◽

Protein Synthesis ◽

Whey Protein ◽

Myofibrillar Protein ◽

Microvascular Perfusion ◽

Anabolic Resistance ◽

Nonessential Amino Acids ◽

Myofibrillar Protein Synthesis

Aging is associated with anabolic resistance, a reduced sensitivity of myofibrillar protein synthesis (MPS) to postprandial hyperaminoacidemia, particularly with low protein doses. Impairments in postprandial skeletal muscle blood flow and/or microvascular perfusion with hyperaminoacidemia and hyperinsulinemia may contribute to anabolic resistance. We examined whether providing citrulline, a precursor for arginine and nitric oxide synthesis, would increase arterial blood flow, skeletal muscle microvascular perfusion, MPS, and signaling through mTORC1. Twenty-one elderly males (65–80 yr) completed acute unilateral resistance exercise prior to being assigned to ingest a high dose (45 g) of whey protein (WHEY) or a low dose (15 g) of whey protein with 10 g of citrulline (WHEY + CIT) or with 10 g of nonessential amino acids (WHEY + NEAA). A primed, continuous infusion of l-[ ring-13C6] phenylalanine with serial muscle biopsies was used to measure MPS and protein phosphorylation, whereas ultrasound was used to measure microvascular circulation under basal and postprandial conditions in both a rested (FED) and exercised (EX-FED) leg. Argininemia was greater in WHEY + CIT vs. WHEY and WHEY + NEAA from 30 to 300 min postexercise ( P < 0.001), but there were no treatment differences in blood flow or microvascular perfusion (all P > 0.05). Phosphorylation of p70S6K-Thr389was greater in WHEY vs. WHEY + NEAA ( P = 0.02). Postprandial MPS was greater in WHEY vs. WHEY + CIT and WHEY + NEAA under both FED (WHEY: ∼128%; WHEY + CIT: ∼56%; WHEY + NEAA: ∼38%) and EX-FED (WHEY: ∼251%; WHEY + CIT: ∼124%; WHEY + NEAA: ∼108%) conditions ( P = 0.003). Citrulline coingestion with a low quantity of protein was ineffective in augmenting the anabolic properties of protein compared with nonessential amino acids.

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Six Weeks of Low-Load Blood Flow Restricted and High-Load Resistance Exercise Training Produce Similar Increases in Cumulative Myofibrillar Protein Synthesis and Ribosomal Biogenesis in Healthy Males

Frontiers in Physiology ◽

10.3389/fphys.2019.00649 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 10

Author(s):

Peter Sieljacks ◽

Jakob Wang ◽

Thomas Groennebaek ◽

Emil Rindom ◽

Jesper Emil Jakobsgaard ◽

...

Keyword(s):

Blood Flow ◽

Protein Synthesis ◽

Load Resistance ◽

Myofibrillar Protein ◽

High Load ◽

Ribosomal Biogenesis ◽

Resistance Exercise Training ◽

Low Load ◽

Myofibrillar Protein Synthesis ◽

Healthy Males

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Effect of Resistance Exercise with Blood Flow Restriction on Muscle Protein Synthesis and mTOR Signaling in Older Men

The FASEB Journal ◽

10.1096/fasebj.23.1_supplement.954.12 ◽

2009 ◽

Vol 23 (S1) ◽

Author(s):

Christopher S Fry ◽

Erin L Glynn ◽

Micah J Drummond ◽

Kyle L Timmerman ◽

Satoshi Fujita ◽

...

Keyword(s):

Blood Flow ◽

Protein Synthesis ◽

Resistance Exercise ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Older Men ◽

Mtor Signaling ◽

Blood Flow Restriction ◽

Flow Restriction

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Blood flow restriction during low-intensity resistance exercise increases S6K1 phosphorylation and muscle protein synthesis

Journal of Applied Physiology ◽

10.1152/japplphysiol.00195.2007 ◽

2007 ◽

Vol 103 (3) ◽

pp. 903-910 ◽

Cited By ~ 246

Author(s):

Satoshi Fujita ◽

Takashi Abe ◽

Micah J. Drummond ◽

Jerson G. Cadenas ◽

Hans C. Dreyer ◽

...

Keyword(s):

Blood Flow ◽

Protein Synthesis ◽

Resistance Exercise ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Mtor Signaling ◽

Blood Flow Restriction ◽

Signaling Proteins ◽

Flow Restriction ◽

Pressure Cuff

Low-intensity resistance exercise training combined with blood flow restriction (REFR) increases muscle size and strength as much as conventional resistance exercise with high loads. However, the cellular mechanism(s) underlying the hypertrophy and strength gains induced by REFR are unknown. We have recently shown that both the mammalian target of rapamycin (mTOR) signaling pathway and muscle protein synthesis (MPS) were stimulated after an acute bout of high-intensity resistance exercise in humans. Therefore, we hypothesized that an acute bout of REFR would enhance mTOR signaling and stimulate MPS. We measured MPS and phosphorylation status of mTOR-associated signaling proteins in six young male subjects. Subjects were studied once during blood flow restriction (REFR, bilateral leg extension exercise at 20% of 1 repetition maximum while a pressure cuff was placed on the proximal end of both thighs and inflated at 200 mmHg) and a second time using the same exercise protocol but without the pressure cuff [control (Ctrl)]. MPS in the vastus lateralis muscle was measured by using stable isotope techniques, and the phosphorylation status of signaling proteins was determined by immunoblotting. Blood lactate, cortisol, and growth hormone were higher following REFR compared with Ctrl ( P < 0.05). Ribosomal S6 kinase 1 (S6K1) phosphorylation, a downstream target of mTOR, increased concurrently with a decreased eukaryotic translation elongation factor 2 (eEF2) phosphorylation and a 46% increase in MPS following REFR ( P < 0.05). MPS and S6K1 phosphorylation were unchanged in the Ctrl group postexercise. We conclude that the activation of the mTOR signaling pathway appears to be an important cellular mechanism that may help explain the enhanced muscle protein synthesis during REFR.

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