Resistance exercise decreases eIF2Bε phosphorylation and potentiates the feeding-induced stimulation of p70S6K1 and rpS6 in young men

2008 ◽  
Vol 295 (2) ◽  
pp. R604-R610 ◽  
Author(s):  
Elisa I. Glover ◽  
Bryan R. Oates ◽  
Jason E. Tang ◽  
Daniel R. Moore ◽  
Mark A. Tarnopolsky ◽  
...  
Keyword(s):  
Resistance Exercise ◽  
Glycogen Synthase ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mammalian Target Of Rapamycin ◽  
Young Men ◽  
Initiation Factor ◽  
Experimental Conditions ◽  
Downstream Target ◽  
Effect Of Feeding

We investigated the effect of resistance exercise and feeding on the activation of signaling proteins involved in translation initiation. Nine young men (23.7 ± 0.41 yr; BMI = 25.5 ± 1.0 kg/m2; means ± SE) were tested twice after they performed a strenuous bout of unilateral resistance exercise, such that their contralateral leg acted as a nonexercised comparator, in either the fasted and fed [1,000 kJ, each 90 min (3 doses): 10 g protein, 41 g carbohydrate, 4 g fat] states. Muscle biopsies were obtained 6 h postexercise from both legs, resulting in four experimental conditions: rest-fasted, rest-fed, exercise-fasted, and exercise-fed. Feeding increased PKB/Akt (Ser473) phosphorylation ( P < 0.05), while exercise increased the phosphorylation of Akt and the downstream 70 kDa S6 protein kinase (p70S6K1, Thr389) and ribosomal protein S6 (rpS6, Ser235/236, Ser240/244; all P < 0.05). The combination of resistance exercise and feeding increased the phosphorylation of p70S6K1 (Thr389) and rpS6 (Ser240/244) above exercise alone ( P < 0.05). Exercise also reduced phosphorylation of the catalytic epsilon subunit of eukaryotic initiation factor 2B (eIF2Bε, Ser540; P < 0.05). Mammalian target of rapamycin (mTOR, Ser2448), glycogen synthase kinase-3β (GSK-3β, Ser9), and focal adhesion kinase (FAK, Tyr576/577) phosphorylation were unaffected by either feeding or resistance exercise (all P > 0.14). In summary, feeding resulted in phosphorylation of Akt, while resistance exercise stimulated phosphorylation of Akt, p70S6K1, rpS6, and dephosphorylation eIF2Bε with a synergistic effect of feeding and exercise on p70S6K1 and its downstream target rpS6. We conclude that resistance exercise potentiates the effect of feeding on the phosphorylation and presumably activation of critical proteins involved in the regulation of muscle protein synthesis in young men.

scholarly journals Relationship between exercise volume and muscle protein synthesis in a rat model of resistance exercise

2017 ◽  
Vol 123 (4) ◽  
pp. 710-716 ◽  
Author(s):  
Riki Ogasawara ◽  
Yuki Arihara ◽  
Junya Takegaki ◽  
Koichi Nakazato ◽  
Naokata Ishii
Keyword(s):  
Protein Synthesis ◽  
Resistance Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mammalian Target Of Rapamycin ◽  
High Volume ◽  
Threshold Effect ◽  
Sprague Dawley ◽  
Downstream Target ◽  
The Relationship

Resistance exercise (RE) volume is recognized as an important factor that stimulates muscle protein synthesis (MPS) and is considered, at least in part, to be involved in the mammalian target of rapamycin complex 1 (mTORC1)-associated signaling. However, the effects of relatively high-volume RE on mTORC1 and MPS remain unclear. In the present study, we used an animal model of RE to investigate the relationship between RE volume and MPS. Male Sprague-Dawley rats were subjected to RE, and muscle samples were obtained 6 h after performing 1, 3, 5, 10, or 20 sets of RE. Although 1 set of RE did not increase MPS [measured by the surface sensing of translation (SUnSET) method], multiple sets (3, 5, 10, and 20 sets) significantly increased MPS. However, the increase in MPS reached a plateau after 3 or 5 sets of RE, and no further increase in MPS was observed with additional RE sets. In contrast to the MPS response, we observed that p70S6K phosphorylation at Thr389, a marker of mTORC1 activity, and Ser240/244 phosphorylation of rpS6, a downstream target of p70S6K, gradually increased with higher RE volume. The above results suggest that the relationship between RE volume and MPS was not linear. Thus the increase in MPS with increasing RE volume saturates before p70S6K phosphorylation, suggesting a threshold effect for the relationship between p70S6K activation and MPS. NEW & NOTEWORTHY The aim of this study was to investigate the relationship between resistance exercise (RE) volume and muscle protein synthesis. We found that the relationship between RE volume and p70S6K phosphorylation was almost linear, but the increase in muscle protein synthesis began to plateau after approximately five sets of RE.

Intravenous administration of amino acids during anesthesia stimulates muscle protein synthesis and heat accumulation in the body

2006 ◽  
Vol 290 (5) ◽  
pp. E882-E888 ◽  
Author(s):  
Ippei Yamaoka ◽  
Masako Doi ◽  
Mitsuo Nakayama ◽  
Akane Ozeki ◽  
Shinji Mochizuki ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase ◽  
Intravenous Administration ◽  
Translation Initiation ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mammalian Target Of Rapamycin ◽  
The Body ◽  
Initiation Factor ◽  
Heat Accumulation

The present study was conducted to determine the contribution of muscle protein synthesis to the prevention of anesthesia-induced hypothermia by intravenous administration of an amino acid (AA) mixture. We examined the changes of intraperitoneal temperature (Tcore) and the rates of protein synthesis ( Ks) and the phosphorylation states of translation initiation regulators and their upstream signaling components in skeletal muscle in conscious (Nor) or propofol-anesthetized (Ane) rats after a 3-h intravenous administration of a balanced AA mixture or saline (Sal). Compared with Sal administration, the AA mixture administration markedly attenuated the decrease in Tcore in rats during anesthesia, whereas Tcore in the Nor-AA group became slightly elevated during treatment. Stimulation of muscle protein synthesis resulting from AA administration was observed in each case, although Ks remained lower in the Ane-AA group than in the Nor-Sal group. AA administration during anesthesia significantly increased insulin concentrations to levels ∼6-fold greater than in the Nor-AA group and enhanced phosphorylation of eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and ribosomal protein S6 protein kinase relative to all other groups and treatments. The alterations in the Ane-AA group were accompanied by hyperphosphorylation of protein kinase B and the mammalian target of rapamycin (mTOR). These results suggest that administration of an AA mixture during anesthesia stimulates muscle protein synthesis via insulin-mTOR-dependent activation of translation initiation regulators caused by markedly elevated insulin and, thereby, facilitates thermal accumulation in the body.

Alcohol impairs leucine-mediated phosphorylation of 4E-BP1, S6K1, eIF4G, and mTOR in skeletal muscle

2003 ◽  
Vol 285 (6) ◽  
pp. E1205-E1215 ◽  
Author(s):  
Charles H. Lang ◽  
Robert A. Frost ◽  
Nobuko Deshpande ◽  
Vinayshree Kumar ◽  
Thomas C. Vary ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Translational Control ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Plasma Concentrations ◽  
Mammalian Target Of Rapamycin ◽  
Initiation Factor ◽  
Skeletal Muscle Protein ◽  
Corticosterone Concentration

Acute alcohol (EtOH) intoxication impairs skeletal muscle protein synthesis. Although this impairment is not associated with a decrease in the total plasma amino acid concentration, EtOH may blunt the anabolic response to amino acids. To examine this hypothesis, rats were administered EtOH or saline (Sal) and 2.5 h thereafter were orally administered either leucine (Leu) or Sal. The gastrocnemius was removed 20 min later to assess protein synthesis and signaling components important in translational control of protein synthesis. Oral Leu increased muscle protein synthesis by the same magnitude in Sal- and EtOH-treated rats. However, the increase in the latter group was insufficient to overcome the suppressive effect of EtOH, and the rate of synthesis remained lower than that observed in rats from the Sal-Sal group. Leu markedly increased phosphorylation of Thr residues 36, 47, and 70 on 4E-binding protein (BP)1 in muscle from rats not receiving EtOH, and this response was associated with a redistribution of eukaryotic initiation factor (eIF) 4E from the inactive eIF4E · 4E-BP1 to the active eIF4E · eIF4G complex. In EtOH-treated rats, the Leu-induced phosphorylation of 4E-BP1 and changes in eIF4E availability were partially abrogated. EtOH also prevented the Leu-induced increase in phosphorylation of eIF4G, the serine/threonine protein kinase S6K1, and the ribosomal protein S6. Moreover, EtOH attenuated the Leu-induced phosphorylation of the mammalian target of rapamycin (mTOR). The ability of EtOH to blunt the anabolic effects of Leu could not be attributed to differences in the plasma concentrations of insulin, insulin-like growth factor I, or Leu. Finally, although EtOH increased the plasma corticosterone concentration, inhibition of glucocorticoid action by RU-486 was unable to prevent EtOH-induced defects in the ability of Leu to stimulate 4E-BP1, S6K1, and mTOR phosphorylation. Hence, ethanol produces a leucine resistance in skeletal muscle, as evidenced by the impaired phosphorylation of 4E-BP1, eIF4G, S6K1, and mTOR, that is independent of elevations in endogenous glucocorticoids.

Phosphorylation of eukaryotic initiation factor eIF2Bε in skeletal muscle during sepsis

2002 ◽  
Vol 283 (5) ◽  
pp. E1032-E1039 ◽  
Author(s):  
Thomas C. Vary ◽  
Gina Deiter ◽  
Scot R. Kimball
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Glycogen Synthase ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Sterile Inflammation ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Skeletal Muscle Protein

We reported that the inhibition of protein synthesis in skeletal muscle during sepsis correlated with reduced eukaryotic initiation factor eIF2B activity. The present studies define changes in eIF2Bε phosphorylation in gastrocnemius of septic animals. eIF2B kinase activity was significantly elevated 175% by sepsis compared with sterile inflammation, whereas eIF2B phosphatase activity was unaffected. Phosphorylation of eIF2Bε-Ser535 was significantly augmented over 2-fold and 2.5-fold after 3 and 5 days and returned to control values after 10 days of sepsis. Phosphorylation of glycogen synthase kinase-3 (GSK-3), a potential upstream kinase responsible for the elevated phosphorylation of eIF2Bε, was significantly reduced over 36 and 41% after 3 and 5 days and returned to control values after 10 days of sepsis. The phosphorylation of PKB, a kinase thought to directly phosphorylate and inactivate GSK-3, was significantly reduced ∼50% on day 3, but not on days 5 or 10, postinfection compared with controls. Treatment of septic rats with TNF-binding protein prevented the sepsis-induced changes in eIF2Bε and GSK-3 phosphorylation, implicating TNF in mediating the effects of sepsis. Thus increased phosphorylation of eIF2Bε via activation of GSK-3 is an important mechanism to account for the inhibition of skeletal muscle protein synthesis during sepsis. Furthermore, the study presents the first demonstration of changes in eIF2Bε phosphorylation in vivo.

Minimal whey protein with carbohydrate stimulates muscle protein synthesis following resistance exercise in trained young men

2007 ◽  
Vol 32 (6) ◽  
pp. 1132-1138 ◽  
Author(s):  
Jason E. Tang ◽  
Joshua J. Manolakos ◽  
Greg W. Kujbida ◽  
Paul J. Lysecki ◽  
Daniel R. Moore ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Resistance Exercise ◽  
Whey Protein ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Young Men ◽  
Skeletal Muscle Protein ◽  
Double Blind ◽  
Exercise Period ◽  
The Impact

Whey protein is a supplemental protein source often used by athletes, particularly those aiming to gain muscle mass; however, direct evidence for its efficacy in stimulating muscle protein synthesis (MPS) is lacking. We aimed to determine the impact of consuming whey protein on skeletal muscle protein turnover in the post-exercise period. Eight healthy resistance-trained young men (age = 21 ± 1 .0 years; BMI = 26.8 ± 0.9 kg/m2 (means ± SE)) participated in a double-blind randomized crossover trial in which they performed a unilateral leg resistance exercise workout (EX: 4 sets of knee extensions and 4 sets of leg press; 8–10 repetitions/set; 80% of maximal), such that one leg was not exercised and acted as a rested (RE) comparator. After exercise, subjects consumed either an isoenergetic whey protein plus carbohydrate beverage (WHEY: 10 g protein and 21 g fructose) or a carbohydrate-only beverage (CHO: 21 g fructose and 10 g maltodextran). Subjects received pulse-tracer injections of l-[ring-2H5]phenylalanine and l-[15N]phenylalanine to measure MPS. Exercise stimulated a rise in MPS in the WHEY-EX and CHO-EX legs, which were greater than MPS in the WHEY-RE leg and the CHO-RE leg (all p < 0.05), respectively. The rate of MPS in the WHEY-EX leg was greater than in the CHO-EX leg (p < 0.001). We conclude that a small dose (10 g) of whey protein with carbohydrate (21 g) can stimulate a rise in MPS after resistance exercise in trained young men that would be supportive of a positive net protein balance, which, over time, would lead to hypertrophy.

scholarly journals The distribution of eukaryotic initiation factor 4E after bouts of resistance exercise is altered by shortening of recovery periods

2020 ◽  
Vol 70 (1) ◽  
Author(s):  
Junya Takegaki ◽  
Riki Ogasawara ◽  
Karina Kouzaki ◽  
Satoshi Fujita ◽  
Koichi Nakazato ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Translation Initiation ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Related Factors ◽  
Eukaryotic Initiation Factor 4E

Abstract Insufficient duration of recovery between resistance exercise bouts reduces the effects of exercise training, but the influence on muscle anabolic responses is not fully understood. Here, we investigated the changes in the distribution of eukaryotic initiation factor (eIF) 4E, a key regulator of translation initiation, and related factors in mouse skeletal muscle after three successive bouts of resistance exercise with three durations of recovery periods (72 h: conventional, 24 h: shorter, and 8 h: excessively shorter). Bouts of resistance exercise dissociated eIF4E from eIF4E binding protein 1, with the magnitude increasing with shorter recovery. Whereas bouts of resistance exercise with 72 h recovery increased the association of eIF4E and eIF4G, those with shorter recovery did not. Similar results were observed in muscle protein synthesis. These results suggest that insufficient recovery inhibited the association of eIF4E and eIF4G, which might cause attenuation of protein synthesis activation after bouts of resistance exercise.

scholarly journals Bolus Arginine Supplementation Affects neither Muscle Blood Flow nor Muscle Protein Synthesis in Young Men at Rest or After Resistance Exercise

2010 ◽  
Vol 141 (2) ◽  
pp. 195-200 ◽  
Author(s):  
Jason E. Tang ◽  
Paul J. Lysecki ◽  
Joshua J. Manolakos ◽  
Maureen J. MacDonald ◽  
Mark A. Tarnopolsky ◽  
...  
Keyword(s):  
Blood Flow ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Blood Flow ◽  
Young Men ◽  
Arginine Supplementation

Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men

2009 ◽  
Vol 107 (3) ◽  
pp. 987-992 ◽  
Author(s):  
Jason E. Tang ◽  
Daniel R. Moore ◽  
Gregory W. Kujbida ◽  
Mark A. Tarnopolsky ◽  
Stuart M. Phillips
Keyword(s):  
Protein Synthesis ◽  
Resistance Exercise ◽  
Soy Protein ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Soy Protein Isolate ◽  
Young Men ◽  
Protein Isolate ◽  
Whey Hydrolysate ◽  
Micellar Casein

This study was designed to compare the acute response of mixed muscle protein synthesis (MPS) to rapidly (i.e., whey hydrolysate and soy) and slowly (i.e., micellar casein) digested proteins both at rest and after resistance exercise. Three groups of healthy young men ( n = 6 per group) performed a bout of unilateral leg resistance exercise followed by the consumption of a drink containing an equivalent content of essential amino acids (10 g) as either whey hydrolysate, micellar casein, or soy protein isolate. Mixed MPS was determined by a primed constant infusion of l-[ ring-13C6]phenylalanine. Ingestion of whey protein resulted in a larger increase in blood essential amino acid, branched-chain amino acid, and leucine concentrations than either casein or soy (P < 0.05). Mixed MPS at rest (determined in the nonexercised leg) was higher with ingestion of faster proteins (whey = 0.091 ± 0.015, soy = 0.078 ± 0.014, casein = 0.047 ± 0.008%/h); MPS after consumption of whey was ∼93% greater than casein (P < 0.01) and ∼18% greater than soy (P = 0.067). A similar result was observed after exercise (whey > soy > casein); MPS following whey consumption was ∼122% greater than casein (P < 0.01) and 31% greater than soy (P < 0.05). MPS was also greater with soy consumption at rest (64%) and following resistance exercise (69%) compared with casein (both P < 0.01). We conclude that the feeding-induced simulation of MPS in young men is greater after whey hydrolysate or soy protein consumption than casein both at rest and after resistance exercise; moreover, despite both being fast proteins, whey hydrolysate stimulated MPS to a greater degree than soy after resistance exercise. These differences may be related to how quickly the proteins are digested (i.e., fast vs. slow) or possibly to small differences in leucine content of each protein.

Postprandial stimulation of muscle protein synthesis is independent of changes in insulin

1997 ◽  
Vol 272 (5) ◽  
pp. E841-E847 ◽  
Author(s):  
E. Svanberg ◽  
L. S. Jefferson ◽  
K. Lundholm ◽  
S. R. Kimball
Keyword(s):  
Protein Synthesis ◽  
Translation Initiation ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Oral Feeding ◽  
Initiation Factor ◽  
Type I ◽  
Eukaryotic Initiation Factor 4E ◽  
Effect Of Feeding ◽  
Stimulation Of

Protein synthesis in skeletal muscle is markedly stimulated (approximately 180% of control rate) within 3 h of oral feeding in mice subjected to an overnight fast (18 h). The stimulation of protein synthesis is the result of a faster rate of translation initiation; however, neither the mediators (i.e., hormones or nutrients) nor the mechanisms responsible for the effect of feeding are well understood. Results of the present study revealed that the amount of eukaryotic initiation factor 4E (eIF-4E) present in the phosphorylated form (i.e., 70%) was not changed after overnight starvation or a subsequent 3-h refeeding period compared with muscles from freely fed mice. In contrast, the phosphorylation state of the eIF-4E binding protein 1 (4E-BP1) was changed with nutritional state. Starvation increased the proportion of the unphosphorylated form of 4E-BP1, whereas feeding promoted a shift to the more highly phosphorylated forms of the protein. Moreover, starvation increased the amount of 4E-BP1 recovered by almost threefold, indicative of an increase in the eIF-4E.4E-BP1 complex. The increased association of 4E-BP1 with eIF-4E was completely reversed within 3 h of feeding. Starvation and refeeding also altered the amount of eIF-4G that coimmunoprecipitated with eIF-4E. However, in contrast to the results obtained for 4E-BP1, starvation decreased the amount of eIF-4G recovered in the eIF-4E immunoprecipitate, suggesting that starvation causes a decrease in the formation of the active eIF-4F complex. The alterations in 4E-BP1 phosphorylation and association of 4E-BP1 and eIF-4G with eIF-4E observed in control mice in response to starvation and refeeding were also observed in diabetic mice exhibiting characteristics of type I or type II diabetes subjected to the same conditions, suggesting that insulin alone does not mediate the observed changes. Thus the integrated feeding response represents an important area of investigation for understanding the regulation of translation initiation.

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