Acute Interval Walking with and without Vascular Occlusion has a Different Effect on 4EBP1 Phosphorylation and Stimulation of the mTOR Signaling Pathway in the Skeletal Muscle of Inactive Men View PDF

Resistance training is a powerful stimulant to increase muscle protein synthesis and consequently increase muscle size which leads to increased maximal strength and muscle hypertrophy [1]. The American School of Sports Medicine has recommended to achieve muscular hypertrophy during resistance training, the intensity of training should be at least 65% Maximum one maximum repetition and any intensity less than this rarely causes hypertrophy and gaining strength [2]. But it has recently been shown that Muscular hypertrophy also occurs during low-intensity resistance training (with 20% of one maximum repetition) along with moderate vascular occlusion [1].

Vascular occlusion exercises or Kaatsu are relatively new exercises that are performed in conditions of restricting blood flow to the muscle. Initially, this exercise was performed in combination with resistance exercises with the aim of increasing hypertrophy and muscle strength. In this regard, several studies have investigated the effect of resistance training with vascular occlusion on skeletal muscle hypertrophy, increased strength as well as neurological, endocrine and cardiovascular responses. It was further found that Kaatsu training is not specific to resistance training. Several studies have been performed on the effect of aerobic exercise with vascular occlusion on aerobic capacity, strength and skeletal muscle volume. It has been shown that low-intensity exercise such as walking when associated with vascular occlusion can significantly improve thigh muscle cross-section and knee joint strength in young and old subjects [3]. Amani in a study of 28 young football players showed that Periodic exercise with vascular occlusion improves aerobic capacity and prevents a decrease in VO2max during the transition period [4].

In this regard, Naserkhani F, et al. (2015) [5], examined the effect of a training session on a treadmill with vascular occlusion on serum levels of growth hormones (GH), insulin-like growth factor-1 (Igf1) and cortisol in inactive female students. Their results showed that a treadmill exercise session with vascular occlusion could further increase catabolic-anabolic hormones in inactive young girls [5]. Bahreinipour MA, et al. (2016) [6], also showed that low-intensity aerobic exercise with vascular occlusion can have a positive effect on the structure of nerve and muscle junctions and reduce the effects of aging in rats [6].

The mechanism of Kaatsu exercises is not specified, but there is a possible mechanism for low-intensity resistance training associated with vascular occlusion includes increased growth hormone secretion due to the accumulation of intramuscular metabolites such as lactate and hydrogen ions in active muscle, local growth factors and intracellular signaling pathways, and more rapid contraction fibers in hypoxic conditions [7]. Evidence suggests that exercise with vascular occlusion, despite low-intensity physical activity (10 to 30% of maximum work capacity), creates a positive training fit and can be a unique method in medicine and sports. In this regard, Abe et al. suggested that vascular occlusion training can be used as an effective exercise method for simultaneous improvement in cardiovascular fitness and muscle fitness [8]. Restriction of active muscle blood flow during low-intensity resistance training (20% -15% of RM1) results in a similar improvement in muscle hypertrophy compared with intense resistance training [9,10]. It has also been shown that low-intensity walking with vascular occlusion can significantly improve strength and hypertrophy [11]. In addition, improvements in endurance capacity (increased oxidative enzymes, capillary density, stroke volume, VO2max, glycogen stores, and decreased heart rate) and an increase in muscle size and strength have been reported with exercise combined with vascular occlusion [12]. For example, Abe et al Combined with 8 weeks of pedaling exercise with vascular occlusion compared with the group without vascular occlusion as a control group, a significant improvement in VO2max (6.4%) as well as a significant increase in the cross-sectional area of the quadriceps muscle. They also reported an increase in the strength of these muscles (3.4, 4.6 and 7.7%, respectively) compared to the control group (0.1, 0.6 and 1.4%, respectively). The results of these studies suggest that obstructive training can be used as an effective training method to simultaneously improve cardiorespiratory endurance and strength and hypertrophy in healthy individuals and even athletes [11].

The process of morphological and metabolic adaptation in skeletal muscle with obstructive training involves a number of signaling mechanisms that are associated with a temporary increase in the number of messenger RNAs for the formation of various genes and the production of encoded proteins. These changes peak 3 to 12 hours after exercise and return to baseline levels after 24 hours [13]. Therefore, the study of cellular responses to various types of obstruction exercises, which ultimately leads to increased synthesis of specific proteins and improved performance, is of interest to sports researchers. The role of obstructive training in improving muscle strength and size has been well documented [8]. And possible molecular mechanisms for this type of adaptation along with resistance obstruction training have been investigated by several studies [14,15].

However, the exact mechanisms of this training method have not been revealed, but some possible mechanisms include; Mechanical stress, metabolic stress, muscle damage, local and systemic hormones, heat shock proteins, IGF-1 / PI3K / Akt / mTOR signal pathway and activity of satellite cells to increase muscle strength and hypertrophy with resistance obstruction training [16]. Fujita S, et al. (2007) [14], also showed that resistance obstruction training, which causes hypertrophy, increases the phosphorylation of Akt / mTOR / S6K1 signal pathway proteins and increases protein synthesis [14]. The authors suggested that the mTORC1 signal pathway may play an important cellular mechanism in hypertrophy associated with resistance obstruction training. In confirmation of these findings, Gundermann DM, et al. (2012) [15], Gundermann DM, et al. (2014) [18] and Fry CS, et al. (2010) [17] in 2010 in separate studies showed that muscle protein synthesis increased even after a period of resistance obstruction training The Akt / mTOR / S6k1 signal pathway is involved in this process [15,17, and 18].

As noted, several studies have reported an increase in muscle size and strength associated with walking with vascular occlusion [8]. For example, Abe T, et al. (2006) [19] reported for the first time a 4% -7% increase in quadriceps muscle volume and an 8% -10% increase in isometric quadriceps muscle strength with 3 weeks of walking training with vascular occlusion. Several studies have since confirmed the initial findings of Abe T, et al. (2006) [19]. The mechanism of muscular hypertrophy with low-intensity obstructive aerobic training is not well understood. However, previous studies have examined several possible scenarios, such as an increase in growth hormone (GH), an increase in insulin-like growth factor (IGF-1), and other myogenic regulatory factors. For example, a very low-intensity obstructive aerobic training (50 m / min) increases blood GH levels [11]. However, these mechanisms are associated with increased muscle strength and volume along with obstructive aerobic training. Other mechanisms may also be involved. One of these possible mechanisms is the key pathway of mTOR cell growth, which is one of the main pathways for protein synthesis and muscle hypertrophy [20,21]. mTOR activity has been shown to be essential for stimulating muscle protein synthesis. Because the use of mTOR inhibitor before resistance activity has prevented protein synthesis along with resistance exercise [22]. The mTOR signal pathway for muscle hypertrophy involves phosphorylation and dephosphorylating of upstream and downstream proteins in muscle cells [21].

mTOR signaling pathway activity controls translation process through eukaryotic initiation factor (eIF2B) [23]. Researchers report that phosphorylation of 4EBP1 is associated with a muscle protein translation machine that is associated with muscle hypertrophy [24]. The mTOR signal pathway through phosphorylation of 4EBP1 prevents the binding of this protein to eIF2B, and allows the copying start factor (eIF2B) to form its own complex to start translating [25]. Therefore, an increase in phosphorylation of 4EBP1 results in an increase in skeletal muscle protein synthesis. Assuming that 4EBP1 protein phosphorylation indicates mTOR signal pathway activity and stimulation of protein synthesis, the present study seeks to determine the role of this protein and its effect on the activity of the mTOR signal pathway as mechanisms of stimulation of increasing muscle volume by measuring the phosphorylation of 4EBP1 protein along with acute obstructive Interval walking. Examining the research background in obstructive training, it is clear that this training method can have beneficial effects on muscle growth, but in this field, less research has been done on cellular and molecular studies in muscle tissue, especially in human specimens.