Article

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

Texas A&M University - Galveston, Galveston, Texas, United States
Journal of Applied Physiology (Impact Factor: 3.06). 10/2007; 103(3):903-10. DOI: 10.1152/japplphysiol.00195.2007
Source: PubMed

ABSTRACT

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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    • "For example, one-legged endurance exercise [45 min at ß50% one-legged peak oxygen uptake ( ˙ V O 2 p eak ) for 4 weeks, four times per week] performed with moderate blood-flow restriction (ß20%) has been demonstrated to increase exercise capacity and ˙ V O 2 max above that performed with a normal blood supply (Sundberg et al. 1993). More recently, BFR using blood-pressure cuffs combined with low-load resistance training has become a popular approach for enhancing adaptations in both skeletal muscle (Burgomaster et al. 2003; Fujita et al. 2007) and the peripheral vasculature, in particular within the conduit arteries and capillary bed (Hunt et al. 2013) Both HIT and SIT have been shown to enhance skeletal muscle capillary growth (Jensen et al. 2004; Cocks et al. 2013, respectively), a critical adaptation to enhance oxygen and substrate delivery. Exercise-induced capillary growth (angiogenesis) is a highly complex process, mediated by signal-transduction pathways involving several transcription and angiogenic growth factors, including hypoxia-inducible factor-1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and the primary capillary growth factor vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Chinsomboon et al. 2009; Geng et al. 2010). "
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    ABSTRACT: This investigation assessed the efficacy of sprint interval training (SIT) combined with post-exercise blood flow restriction as a novel approach to enhance maximal aerobic physiology and performance. In Study 1, a between groups design determined whether 4 weeks (2 d/wk) of SIT (repeated 30 s maximal sprint cycling) combined with post-exercise blood flow restriction (BFR) enhanced maximal oxygen uptake (VO2max ) and 15 km cycling time trial performance (15km-TT) compared to SIT alone (CON) in trained individuals. VO2max increased after BFR by 4.5% (P = 0.01) but was unchanged after CON. There was no difference in 15km-TT performance after CON or BFR. In Study 2, using a repeated measures design, participants performed an acute bout of either BFR or CON. Muscle biopsies were taken before and after exercise to examine the activation of signalling pathways regulating angiogenesis and mitochondrial biogenesis. Phosphorylation of p38MAPK(Thr180/Tyr182) increased by a similar extent after CON and BFR. There was no difference in the magnitude of increase in PGC-1α, VEGF and VEGFR-2 mRNA expression between protocols, however HIF-1α mRNA expression increased (P = 0.04) at 3 h only after BFR. We have demonstrated the potency of combining BFR with SIT in increasing VO2max in trained individuals, however this did not translate to an enhanced exercise performance. SIT alone did not induce any observable adaptation. Although the mechanisms are not fully understood, we present preliminary evidence that BFR led to enhanced HIF-1α mediated cell signalling. This article is protected by copyright. All rights reserved.
    Preview · Article · Sep 2015 · Experimental physiology
    • "Resistance exercise performed to failure elevates muscle protein synthesis independent of volume (sets × reps) or % one repetition maximum (1RM) load (Burd et al., 2010b; Mitchell et al., 2012). For example, low-load blood flow-restricted exercise has been shown to elicit significant increases in muscle hypertrophy and strength (Fujita et al., 2007; Takada et al., 2012). Furthermore , investigations that controlled relative %1RM training load and volume reported that repetition failure led to significantly greater gains in muscular strength (Rooney et al., 1994; Drinkwater et al., 2005). "
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    ABSTRACT: This investigation sought to determine the effect of resistance training to failure on functional, structural and neural elbow flexor muscle adaptation. Twenty-eight males completed a 4-week familiarization period and were then counterbalanced on the basis of responsiveness across; non-failure rapid shortening (RS; rapid concentric, 2 s eccentric), non-failure stretch-shortening (SSC; rapid concentric, rapid eccentric), and failure control (C, 2 s concentric, 2 s eccentric), for a 12-week unilateral elbow flexor resistance training regimen, 3 × week using 85% of one repetition maximum (1RM). 1RM, maximal voluntary contraction (MVC), muscle cross-sectional area (CSA), and muscle activation (EMGRMS ) of the agonist, antagonist, and stabilizer muscles were assessed before and after the 12-week training period. The average number of repetitions per set was significantly lower in RS 4.2 [confidence interval (CI): 4.2, 4.3] and SSC 4.2 (CI: 4.2, 4.3) compared with C 6.1 (CI: 5.8, 6.4). A significant increase in 1RM (30.5%), MVC (13.3%), CSA (11.4%), and agonist EMGRMS (22.1%) was observed; however, no between-group differences were detected. In contrast, antagonist EMGRMS increased significantly in SSC (40.5%) and C (23.3%), but decreased in RS (13.5%). Similar adaptations across the three resistance training regimen suggest repetition failure is not critical to elicit significant neural and structural changes to skeletal muscle. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    No preview · Article · Apr 2015 · Scandinavian Journal of Medicine and Science in Sports
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    • "On the other hand, the mTOR signalling pathway is a potent positive regulator of skeletal muscle size and plays a significant role in stimulating translation initiation and muscle protein synthesis. A previous BFR study (Fujita et al., 2007) reported that increased muscle protein synthesis through the mTOR signalling pathway was observed in LI-BFR exercise as well as HI exercise. Therefore, it appears that both myostatin and mTOR signalling pathways may have a potent influence on decreases in muscle size during a detraining period. "
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    ABSTRACT: We investigated the effects of 3 weeks of detraining on muscle cross-sectional area (CSA) and one-repetition maximum strength (1-RM) in young men who had previously participated in 6 weeks (3 days week−1) of bench press training [blood flow restricted low-intensity (LI-BFR; n = 10, 20% 1-RM) or high-intensity (HI; n = 7, 75% 1-RM)]. Bench press 1-RM and muscle CSA of triceps brachii (TB) and pectoralis major (PM) were evaluated before (pre) and after training period (post) as well as after detraining period (detraining). Bench press 1-RM was higher at both post and detraining than at pre for LI-BFR (P<0·01) and the HI (P<0·01). TB and PM muscle CSA were higher at both post and detraining than at pre for the HI group (P<0·01), while the LI-BFR group only increased (P<0·01) at post. Relative dynamic strength (1-RM divided by TB muscle CSA) was higher at both post and detraining than at pre for the HI group (P<0·01), while the LI-BFR group only increased (P<0·01) at detraining. In conclusion, increased muscle strength following 6 weeks of training with LI-BFR as well as HI was well preserved at 3 weeks of detraining. HI-induced muscle strength appears to be dependent upon both neural adaptations and muscle hypertrophy with training and detraining. On the other hand, LI-BFR-induced muscle strength appears to be related primarily to muscle hypertrophy with training and to neural adaptations with detraining.
    Full-text · Article · May 2014 · Clinical Physiology and Functional Imaging
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