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

Gundermann, David M.; Walker, D.M.H.; Reidy, Paul T.; Borack, Michael; Dickinson, Jared M.; Volpi, Elena; Rasmussen, Blake B.

doi:10.1152/ajpendo.00600.2013

Cited by 102 publications

(75 citation statements)

References 37 publications

(64 reference statements)

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“…It can be hypothesized that these alternative mechanisms responsible for muscle growth (i.e., metabolic accumulation, cell swelling) may be able to augment the muscle hypertrophic response during low-load BFR training in the absence of sufficient mechanical tension. Additionally, while both low-load BFR training and traditional high-load training may work through alternate mechanisms, they appear to both be reliant on the activation of the mechanistic target of rapamycin (mTOR) pathway, as evident by the blunted protein synthetic response when rapamycin, an mTOR suppressor, is administered [13,14]. While an in-depth review of the mechanisms behind BFR-induced growth is outside the scope of this review and can be found elsewhere [15], one constant that seems to be important for robust muscle hypertrophy is a high level of muscle activation [2].…”

Section: Introductionmentioning

confidence: 99%

The Effects of Blood Flow Restriction on Upper-Body Musculature Located Distal and Proximal to Applied Pressure

et al. 2015

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Blood flow restriction (BFR) training has been shown to increase muscle size and strength when combined with low-load [20-30 % one-repetition maximum (1RM)] resistance training in the lower body. Fewer studies have examined low-load BFR training in combination with upper body exercise, which may differ as some musculature cannot be directly restricted by the BFR stimulus (chest, shoulders). The objective of this study was to examine muscle adaptations occurring in the upper body in response to low-load BFR training. Google Scholar, PubMed, and SPORTDiscus were searched through July 2015 using the key phrases 'blood flow restriction training', 'occlusion resistance training', and 'KAATSU'. Upper body training studies implementing the BFR stimulus and providing a pre and post measure of muscle size and/or strength were included. A total of 19 articles met the inclusion criteria for this review. The effectiveness of low-load BFR training appears to be minimally impacted by alterations to the intensity and restrictive pressures used; however, the ability to quantitatively analyze our results was limited by unstandardized protocols. Low-load BFR training increased muscle size and strength in limbs located proximal (chest, shoulders) and distal (biceps, triceps) to the restrictive stimulus; while volume-matched exercise in the absence of BFR did not elicit beneficial muscle adaptations. Some of the musculature in the upper body cannot be directly restricted by the application of BFR. Despite this, increases in muscle size and strength were observed in muscles placed under direct and indirect BFR.

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Section: Introductionmentioning

confidence: 99%

The Effects of Blood Flow Restriction on Upper-Body Musculature Located Distal and Proximal to Applied Pressure

et al. 2015

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“…Gundermann et al [13] observed that the phosphorylation of mTORC1 at the Ser2448 site was increased as compared with baseline values and higher than that in the control group after TVO. Another study by Gundermann et al [2], with a view to verifying whether the signalling of mTORC1 is required for the stimulation of muscle protein synthesis after a TVO session, proved that phosphorylation of mTOR at the Ser2448 site was increased 3 hours after a training session in young adults, and differences for the group treated with rapamycin were found 6 and 24 hours after the stimulus. Furthermore, Drummond et al [47] did not demonstrate acute alterations in mRNA expression for mTOR in 6 young male individuals.…”

Section: Mtor Signalling Pathwaymentioning

confidence: 98%

“…Some studies have analysed the activity of mTOR [1, 2,12,13] or the expression of mRNA [47,48] for this specific protein and its targets downstream and upstream.…”

Section: Mtor Signalling Pathwaymentioning

confidence: 99%

“…TVO has been shown to increase the S6K1 phosphorylation at the Thr389 site, both in young individuals [2,12,13] and elderly males [1], activating it. However, there appears not to be a change in mRNA expression of this protein after a TVO session [47].…”

Section: Mtor Signalling Pathwaymentioning

confidence: 99%

“…Training with vascular occlusion (TVO), or KAATSU training, has been widely studied in recent years [1][2][3][4][5]. Research has shown that this method promotes increases in muscular strength and hypertrophy in a manner similar to conventional strength training (CT) [3,6].…”

Section: Introductionmentioning

confidence: 99%

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Strength training with vascular occlusion: a review of possible adaptive mechanisms

Castro¹,

Aquino²,

Berti³

et al. 2018

Hum Mov.

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Strength training with blood flow restriction, or KAATSU training, has been shown to be as effective as conventional strength training to promote muscular strength and hypertrophy. Several mechanisms have been suggested as hypotheses to explain the adaptations arising from this training method. Among these is metabolic stress, which exerts important physiological effects and may influence the training adaptations in question. In addition, hypoxia produced by the technique may change the neural recruitment pattern. Growth hormone (GH) concentrations increase as a result of practicing this method, which can trigger an increase in plasmatic and, perhaps, muscular insulin-like growth factor-1 (IGF-1) concentrations. The increase in concentrations of these factors can play a leading role in responses to KAATSU training. Among the effects of the GH/IGF-1 axis in muscle cells is the increase in the signalling pathway activity of the mammalian target of rapamycin (mTOR), which has been associated with increased protein synthesis. On the other hand, the decrease in the activity of the myostatin pathway, which has an antagonistic effect to mTOR, has been demonstrated after training with occlusion. Other factors, such as increases in the expression of heat shock proteins, may play an important role in adaptations to exercise. Nitric oxide synthase could increase nitric oxide concentration, which in turn has an effect on satellite cells and blood flow. However, despite the results obtained, the transfer to other situations (e.g. speed sports) is not yet clear.

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Emerging role of TAK1 in the regulation of skeletal muscle mass

2023

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Maintenance of skeletal muscle mass and strength throughout life is crucial for heathy living and longevity. Several signaling pathways have been implicated in the regulation of skeletal muscle mass in adults. TGF-β-activated kinase 1 (TAK1) is a key protein, which coordinates the activation of multiple signaling pathways. Recently, it was discovered that TAK1 is essential for the maintenance of skeletal muscle mass and myofiber hypertrophy following mechanical overload. Forced activation of TAK1 in skeletal muscle causes hypertrophy and attenuates denervation-induced muscle atrophy. TAK1-mediated signaling in skeletal muscle promotes protein synthesis, redox homeostasis, mitochondrial health, and integrity of neuromuscular junctions. In this article, we have reviewed the role and potential mechanisms through which TAK1 regulates skeletal muscle mass and growth. We have also proposed future areas of research that could be instrumental in exploring TAK1 as therapeutic target for improving muscle mass in various catabolic conditions and diseases.

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

Abstract: Gundermann DM, Walker DK, Reidy PT, Borack MS, Dickinson JM, Volpi E, Rasmussen BB. Activation of mTORC1 signaling and protein synthesis in human muscle following blood flow restriction exercise is inhibited by rapamycin.

Cited by 102 publications

References 37 publications

The Effects of Blood Flow Restriction on Upper-Body Musculature Located Distal and Proximal to Applied Pressure

The Effects of Blood Flow Restriction on Upper-Body Musculature Located Distal and Proximal to Applied Pressure

Strength training with vascular occlusion: a review of possible adaptive mechanisms

Emerging role of TAK1 in the regulation of skeletal muscle mass

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