scholarly journals Castration alters protein balance after high-frequency muscle contraction

2017 ◽  
Vol 122 (2) ◽  
pp. 264-272 ◽  
Author(s):  
Jennifer L. Steiner ◽  
David H. Fukuda ◽  
Michael L. Rossetti ◽  
Jay R. Hoffman ◽  
Bradley S. Gordon
Keyword(s):  
Protein Synthesis ◽  
Resistance Exercise ◽  
Protein Content ◽  
High Frequency ◽  
Muscle Contractions ◽  
Protein Balance ◽  
Fasted State ◽  
Mtorc1 Signaling ◽  
Potential Contributor ◽  
The Relationship

Resistance exercise increases muscle mass by shifting protein balance in favor of protein accretion. Androgens independently alter protein balance, but it is unknown whether androgens alter this measure after resistance exercise. To answer this, male mice were subjected to sham or castration surgery 7–8 wk before undergoing a bout of unilateral, high-frequency, electrically induced muscle contractions in the fasted or refed state. Puromycin was injected 30 min before euthanasia to measure protein synthesis. The tibialis anterior was analyzed 4 h postcontraction. In fasted mice, neither basal nor stimulated rates of protein synthesis were affected by castration despite lower phosphorylation of mechanistic target of rapamycin in complex 1 (mTORC1) substrates [p70S6K1 (Thr389) and 4E-BP1 (Ser65)]. Markers of autophagy (LC3 II/I ratio and p62 protein content) were elevated by castration, and these measures remained elevated above sham values after contractions. Furthermore, in fasted mice, the protein content of Regulated in Development and DNA Damage 1 (REDD1) was correlated with LC3 II/I in noncontracted muscle, whereas phosphorylation of uncoordinated like kinase 1 (ULK1) (Ser757) was correlated with LC3 II/I in the contracted muscle. When mice were refed before contractions, protein synthesis and mTORC1 signaling were not affected by castration in either the noncontracted or contracted muscle. Conversely, markers of autophagy remained elevated in the muscles of refed, castrated mice even after contractions. These data suggest the castration-mediated elevation in baseline autophagy reduces the absolute positive shift in protein balance after muscle contractions in the refed or fasted states. NEW & NOTEWORTHY In the absence of androgens, markers of autophagy were elevated, and these could not be normalized by muscle contractions. In the fasted state, REDD1 was identified as a potential contributor to autophagy in noncontracted muscle, whereas phosphorylation of ULK1 may contribute to this process in the contracted muscle. In the refed state, markers of autophagy remain elevated in both noncontracted and contracted muscles, but the relationship with REDD1 and ULK1 (Ser757) no longer existed.

A Clinically Relevant Decrease in Contractile Force Differentially Regulates Control of Glucocorticoid Receptor Translocation in Mouse Skeletal Muscle

2021 ◽  
Author(s):  
Kirsten R. Dunlap ◽  
Jennifer L. Steiner ◽  
Michael L. Rossetti ◽  
Scot R. Kimball ◽  
Bradley S. Gordon
Keyword(s):  
Protein Synthesis ◽  
Glucocorticoid Receptor ◽  
Resistance Exercise ◽  
Muscle Atrophy ◽  
Nuclear Translocation ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Contractile Force ◽  
Force Generation ◽  
Protein Balance

Muscle atrophy decreases physical function and overall health. Increased glucocorticoid production and/or use of prescription glucocorticoids can significantly induce muscle atrophy by activating the glucocorticoid receptor thereby transcribing genes that shift protein balance in favor of net protein degradation. While mechanical overload can blunt glucocorticoid-induced atrophy in young muscle, those affected by glucocorticoids generally have impaired force generation. It is unknown whether contractile force alters the ability of resistance exercise to mitigate glucocorticoid receptor translocation and induce a desirable shift in protein balance when glucocorticoids are elevated. In the present study, mice were subjected to a single bout of unilateral, electrically induced muscle contractions by stimulating the sciatic nerve at 100 Hz or 50 Hz frequencies to elicit high force or moderate force contractions of the tibialis anterior, respectively. Dexamethasone was used to activate the glucocorticoid receptor. Dexamethasone increased glucocorticoid signaling, including nuclear translocation of the receptor, but this was mitigated only by high force contractions. The ability of high force contractions to mitigate glucocorticoid receptor translocation coincided with a contraction-mediated increase in muscle protein synthesis, which did not occur in the dexamethasone treated mice subjected to moderate force contractions. Though moderate force contractions failed to increase protein synthesis following dexamethasone treatment, both high and moderate force contractions blunted the glucocorticoid-mediated increase in LC3 II:I marker of autophagy. Thus, these data show that force generation is important for the ability of resistance exercise to mitigate glucocorticoid receptor translocation and promote a desirable shift in protein balance when glucocorticoids are elevated.

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.

scholarly journals Reactive hyperemia is not responsible for stimulating muscle protein synthesis following blood flow restriction exercise

2012 ◽  
Vol 112 (9) ◽  
pp. 1520-1528 ◽  
Author(s):  
David M. Gundermann ◽  
Christopher S. Fry ◽  
Jared M. Dickinson ◽  
Dillon K. Walker ◽  
Kyle L. Timmerman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Reactive Hyperemia ◽  
Blood Flow Restriction ◽  
Flow Restriction ◽  
Low Intensity ◽  
Mtorc1 Signaling

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.

Effect of an Amino Acid, Protein, and Carbohydrate Mixture on Net Muscle Protein Balance after Resistance Exercise

2004 ◽  
Vol 14 (3) ◽  
pp. 255-271 ◽  
Author(s):  
Elisabet Børsheim ◽  
Asle Aarsland ◽  
Robert R. Wolfe
Keyword(s):  
Protein Synthesis ◽  
Resistance Exercise ◽  
Whey Protein ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Vastus Lateralis ◽  
Area Under The Curve ◽  
Constant Infusion ◽  
Delayed Response ◽  
Protein Balance

This study tests the hypotheses that (a) a mixture of whey protein, amino acids (AA), and carbohydrates (CHO) stimulates net muscle protein synthesis to a greater extent than isoenergetic CHO alone after resistance exercise; and (b) that the stimulatory effect of a protein, AA, and CHO mixture will last beyond the 1 st hour after intake. Eight subjects participated in 2 trials. In one (PAAC), they ingested 77.4 g CHO, 17.5 g whey protein, and 4.9 g AA 1 hr after resistance exercise. In the other (CON), 100 g CHO was ingested instead. They received a primed constant infusion of L-[2H5]-phenylalanine, and samples from femoral artery and vein, and biopsies from vastus lateralis were obtained. The area under the curve for net uptake of phenylalanine into muscle above pre-drink value was 128 ±42 mg • leg-1 (PAAC) versus 32 ± 10 mg - leg-1 (CON) for the 3 hr after the drink (p = .04). The net protein balance response to the mixture consisted of two components, one rapid immediate response, and a smaller delayed response about 90 min after drink, whereas in CON only a small delayed response was seen. We conclude that after resistance exercise, a mixture of whey protein, AA, and CHO stimulated muscle protein synthesis to a greater extent than isoenergetic CHO alone. Further, compared to previously reported findings, the addition of protein to an AA + CHO mixture seems to extend the anabolic effect.

scholarly journals Postexercise net protein synthesis in human muscle from orally administered amino acids

1999 ◽  
Vol 276 (4) ◽  
pp. E628-E634 ◽  
Author(s):  
Kevin D. Tipton ◽  
Arny A. Ferrando ◽  
Stuart M. Phillips ◽  
David Doyle ◽  
Robert R. Wolfe
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Resistance Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Random Order ◽  
Essential Amino Acids ◽  
Constant Infusion ◽  
Protein Balance

We examined the response of net muscle protein synthesis to ingestion of amino acids after a bout of resistance exercise. A primed, constant infusion ofl-[ ring-2H5]phenylalanine was used to measure net muscle protein balance in three male and three female volunteers on three occasions. Subjects consumed in random order 1 liter of 1) a mixed amino acid (40 g) solution (MAA), 2) an essential amino acid (40 g) solution (EAA), and 3) a placebo solution (PLA). Arterial amino acid concentrations increased ∼150–640% above baseline during ingestion of MAA and EAA. Net muscle protein balance was significantly increased from negative during PLA ingestion (−50 ± 23 nmol ⋅ min−1 ⋅ 100 ml leg volume−1) to positive during MAA ingestion (17 ± 13 nmol ⋅ min−1 ⋅ 100 ml leg volume−1) and EAA (29 ± 14 nmol ⋅ min−1 ⋅ 100 ml leg volume−1; P < 0.05). Because net balance was similar for MAA and EAA, it does not appear necessary to include nonessential amino acids in a formulation designed to elicit an anabolic response from muscle after exercise. We concluded that ingestion of oral essential amino acids results in a change from net muscle protein degradation to net muscle protein synthesis after heavy resistance exercise in humans similar to that seen when the amino acids were infused.

scholarly journals Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling

2009 ◽  
Vol 106 (4) ◽  
pp. 1374-1384 ◽  
Author(s):  
Micah J. Drummond ◽  
Hans C. Dreyer ◽  
Christopher S. Fry ◽  
Erin L. Glynn ◽  
Blake B. Rasmussen
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Human Skeletal Muscle ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Essential Amino Acids ◽  
Skeletal Muscle Protein ◽  
Mtorc1 Signaling

In this review we discuss current findings in the human skeletal muscle literature describing the acute influence of nutrients (leucine-enriched essential amino acids in particular) and resistance exercise on muscle protein synthesis and mammalian target of rapamycin complex 1 (mTORC1) signaling. We show that essential amino acids and an acute bout of resistance exercise independently stimulate human skeletal muscle protein synthesis. It also appears that ingestion of essential amino acids following resistance exercise leads to an even larger increase in the rate of muscle protein synthesis compared with the independent effects of nutrients or muscle contraction. Until recently the cellular mechanisms responsible for controlling the rate of muscle protein synthesis in humans were unknown. In this review, we highlight new studies in humans that have clearly shown the mTORC1 signaling pathway is playing an important regulatory role in controlling muscle protein synthesis in response to nutrients and/or muscle contraction. We propose that essential amino acid ingestion shortly following a bout of resistance exercise is beneficial in promoting skeletal muscle growth and may be useful in counteracting muscle wasting in a variety of conditions such as aging, cancer cachexia, physical inactivity, and perhaps during rehabilitation following trauma or surgery.

scholarly journals Reduced REDD1 expression contributes to activation of mTORC1 following electrically induced muscle contraction

2014 ◽  
Vol 307 (8) ◽  
pp. E703-E711 ◽  
Author(s):  
Bradley S. Gordon ◽  
Jennifer L. Steiner ◽  
Charles H. Lang ◽  
Leonard S. Jefferson ◽  
Scot R. Kimball
Keyword(s):  
Protein Synthesis ◽  
Protein Expression ◽  
Muscle Contractions ◽  
Wild Type ◽  
Fed State ◽  
Mtorc1 Signaling ◽  
Single Bout ◽  
Exercise Induced ◽  
Mtor Complex 1

Regulated in DNA damage and development 1 (REDD1) is a repressor of mTOR complex 1 (mTORC1) signaling. In humans, REDD1 mRNA expression in skeletal muscle is repressed following resistance exercise in association with activation of mTORC1. However, whether REDD1 protein expression is also reduced after exercise and if so to what extent the loss contributes to exercise-induced activation of mTORC1 is unknown. Thus, the purpose of the present study was to examine the role of REDD1 in governing the response of mTORC1 and protein synthesis to a single bout of muscle contractions. Eccentric contractions of the tibialis anterior were elicited via electrical stimulation of the sciatic nerve in male mice in either the fasted or fed state or in fasted wild-type or REDD1-null mice. Four hours postcontractions, mTORC1 signaling and protein synthesis were elevated in fasted mice in association with repressed REDD1 expression relative to nonstimulated controls. Feeding coupled with contractions further elevated mTORC1 signaling, whereas REDD1 protein expression was repressed compared with either feeding or contractions alone. Basal mTORC1 signaling and protein synthesis were elevated in REDD1-null compared with wild-type mice. The magnitude of the increase in mTORC1 signaling was similar in both wild-type and REDD1-null mice, but, unlike wild-type mice, muscle contractions did not stimulate protein synthesis in mice deficient for REDD1, presumably because basal rates were already elevated. Overall, the data demonstrate that REDD1 expression contributes to the modulation of mTORC1 signaling following feeding- and contraction-induced activation of the pathway.

scholarly journals Dietary Aronia melanocarpa extract enhances mTORC1 signaling, but has no effect on protein synthesis and protein breakdown-related signaling, in response to resistance exercise in rat skeletal muscle

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Yuhei Makanae ◽  
Satoru Ato ◽  
Kohei Kido ◽  
Satoshi Fujita
Keyword(s):  
Protein Synthesis ◽  
Resistance Exercise ◽  
Signaling Pathway ◽  
Ursolic Acid ◽  
Protein Metabolism ◽  
Gastrocnemius Muscle ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Aronia Melanocarpa ◽  
Mtorc1 Signaling

Abstract Background Ursolic acid altered muscle protein metabolism in normal and resting conditions after acute resistance exercise, suggesting that eating fruits rich in ursolic acid could enhance muscle protein synthesis and decrease muscle degradation. Aronia melanocarpa, a member of the family Rosaceae and native to North America and Eastern Canada, is rich in ursolic acid. In this study, we examined the effects of A. melanocarpa extract (AME) supplementation on the mTORC1 signaling pathway and muscle degradation-related factors in rats, both alone and in combination with resistance exercise. Methods Male Sprague-Dawley rats were divided into AME and normal chow (NOR) groups. AME group was fed chow providing a dose of 3 g/kg of AME and 115 mg/kg of ursolic acid for 7 days, whereas NOR rats were fed normal powder chow. The right gastrocnemius muscle of each animal was isometrically exercised (5 sets of ten 3-s contractions, with a 7-s interval between contractions and 3-min rest intervals between sets), while the left gastrocnemius muscle served as an internal control. Western blotting and real-time polymerase chain reaction were used to assess expression of factors involved in the mTORC1 signaling pathway and muscle degradation. Results At 1 h after resistance exercise, phosphorylation of ERK1/2 was significantly increased by AME consumption. At 6 h after resistance exercise, AME consumption significantly increased the phosphorylation of Akt, p70S6K, rpS6, and AMPK. It also increased MAFbx expression. Furthermore, AME significantly increased the phosphorylation of p70S6K and rpS6 in response to resistance exercise. However, AME did not increase muscle protein synthesis (MPS) after resistance exercise. AME did not affect the expression of any of the mediators of protein degradation, with the exception of MAFbx. Conclusions Dietary AME enhanced mTORC1 activation in response to resistance exercise without increasing MPS. Moreover, it neither accelerated muscle protein degradation nor otherwise negatively affected protein metabolism. Further study is needed to clarify the effect of the combination of AME and chronic resistance training on muscle hypertrophy.

Age-related Differences In Muscle Protein Synthesis And mTORC1 Signaling Following Resistance Exercise: A 24-hour Time-course

2010 ◽  
Vol 42 ◽  
pp. 63
Author(s):  
Christopher S. Fry ◽  
Micah J. Drummond ◽  
Erin L. Glynn ◽  
Jared M. Dickinson ◽  
David M. Gundermann ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Resistance Exercise ◽  
Time Course ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Age Related ◽  
Mtorc1 Signaling
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