scholarly journals Regulation of Muscle Growth in Early Postnatal Life in a Swine Model

2019 ◽  
Vol 7 (1) ◽  
pp. 309-335 ◽  
Author(s):  
Marko Rudar ◽  
Marta L. Fiorotto ◽  
Teresa A. Davis
Keyword(s):  
Protein Synthesis ◽  
Satellite Cells ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Cell Activity ◽  
Postnatal Period ◽  
Postnatal Life ◽  
Swine Model ◽  
Satellite Cell Activity

Skeletal muscle growth during the early postnatal period is rapid in the pig and dependent on the capacity of muscle to respond to anabolic and catabolic stimuli. Muscle mass is driven by the balance between protein synthesis and degradation. Among these processes, muscle protein synthesis in the piglet is exceptionally sensitive to the feeding-induced postprandial changes in insulin and amino acids, whereas muscle protein degradation is affected only during specific catabolic states. The developmental decline in the response of muscle to feeding is associated with changes in the signaling pathways located upstream and downstream of the mechanistic target of rapamycin protein complex. Additionally, muscle growth is supported by an accretion of nuclei derived from satellite cells. Activated satellite cells undergo proliferation, differentiation, and fusion with adjacent growing muscle fibers. Enhancing early muscle growth through modifying protein synthesis, degradation, and satellite cell activity is key to maximizing performance, productivity, and lifelong pig health.

scholarly journals Proteasome- and Calpain-Mediated Proteolysis, but Not Autophagy, Is Required for Leucine-Induced Protein Synthesis in C2C12 Myotubes

Physiologia ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 22-33
Author(s):  
Shelby C. Osburn ◽  
Christopher G. Vann ◽  
David D. Church ◽  
Arny A. Ferrando ◽  
Michael D. Roberts
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Proteasome Inhibition ◽  
Coupled Processes ◽  
C2c12 Myotubes ◽  
Calpain Inhibitor ◽  
Tightly Coupled

Muscle protein synthesis and proteolysis are tightly coupled processes. Given that muscle growth is promoted by increases in net protein balance, it stands to reason that bolstering protein synthesis through amino acids while reducing or inhibiting proteolysis could be a synergistic strategy in enhancing anabolism. However, there is contradictory evidence suggesting that the proper functioning of proteolytic systems in muscle is required for homeostasis. To add clarity to this issue, we sought to determine if inhibiting different proteolytic systems in C2C12 myotubes in conjunction with acute and chronic leucine treatments affected markers of anabolism. In Experiment 1, myotubes underwent 1-h, 6-h, and 24-h treatments with serum and leucine-free DMEM containing the following compounds (n = 6 wells per treatment): (i) DMSO vehicle (CTL), (ii) 2 mM leucine + vehicle (Leu-only), (iii) 2 mM leucine + 40 μM MG132 (20S proteasome inhibitor) (Leu + MG132), (iv) 2 mM leucine + 50 μM calpeptin (calpain inhibitor) (Leu + CALP), and (v) 2 mM leucine + 1 μM 3-methyladenine (autophagy inhibitor) (Leu + 3MA). Protein synthesis levels significantly increased (p < 0.05) in the Leu-only and Leu + 3MA 6-h treatments compared to CTL, and levels were significantly lower in Leu + MG132 and Leu + CALP versus Leu-only and CTL. With 24-h treatments, total protein yield was significantly lower in Leu + MG132 cells versus other treatments. Additionally, the intracellular essential amino acid (EAA) pool was significantly greater in 24-h Leu + MG132 treatments versus other treatments. In a follow-up experiment, myotubes were treated for 48 h with CTL, Leu-only, and Leu + MG132 for morphological assessments. Results indicated Leu + MG132 yielded significantly smaller myotubes compared to CTL and Leu-only. Our data are limited in scope due to the utilization of select proteolysis inhibitors. However, this is the first evidence to suggest proteasome and calpain inhibition with MG132 and CALP, respectively, abrogate leucine-induced protein synthesis in myotubes. Additionally, longer-term Leu + MG132 treatments translated to an atrophy phenotype. Whether or not proteasome inhibition in vivo reduces leucine- or EAA-induced anabolism remains to be determined.

scholarly journals Circadian regulation of muscle growth independent of locomotor activity

2020 ◽  
Vol 117 (49) ◽  
pp. 31208-31218
Author(s):  
Jeffrey J. Kelu ◽  
Tapan G. Pipalia ◽  
Simon M. Hughes
Keyword(s):  
Physical Activity ◽  
Protein Synthesis ◽  
Circadian Clock ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Diurnal Variations ◽  
Dominant Negative ◽  
Messenger Rnas ◽  
Free Running

Muscle tissue shows diurnal variations in function, physiology, and metabolism. Whether such variations are dependent on the circadian clock per se or are secondary to circadian differences in physical activity and feeding pattern is unclear. By measuring muscle growth over 12-h periods in live prefeeding larval zebrafish, we show that muscle grows more during day than night. Expression of dominant negative CLOCK (ΔCLK), which inhibits molecular clock function, ablates circadian differences and reduces muscle growth. Inhibition of muscle contraction reduces growth in both day and night, but does not ablate the day/night difference. The circadian clock and physical activity are both required to promote higher muscle protein synthesis during the day compared to night, whereas markers of protein degradation,murfmessenger RNAs, are higher at night. Proteasomal inhibitors increase muscle growth at night, irrespective of physical activity, but have no effect during the day. Although physical activity enhances TORC1 activity, and the TORC1 inhibitor rapamycin inhibits clock-driven daytime growth, no effect on muscle growth at night was detected. Importantly, day/night differences in 1) muscle growth, 2) protein synthesis, and 3)murfexpression all persist in entrained larvae under free-running constant conditions, indicating circadian drive. Removal of circadian input by exposure to either permanent darkness or light leads to suboptimal muscle growth. We conclude that diurnal variations in muscle growth and metabolism are a circadian property that is independent of, but augmented by, physical activity, at least during development.

Signal transduction pathways that regulate muscle growth

2008 ◽  
Vol 44 ◽  
pp. 99-108 ◽  
Author(s):  
Henning Wackerhage ◽  
Aivaras Ratkevicius
Keyword(s):  
Signal Transduction ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Mammalian Target Of Rapamycin ◽  
High Growth ◽  
Signal Transduction Pathways ◽  
Cellular Functions

Progressive high-resistance exercise with 8–12 repetitions per set to near failure for beginners and 1–12 repetitions for athletes will increase muscle protein synthesis for up to 72 h; approx. 20 g of protein, especially when ingested directly after exercise, will promote high growth by elevating protein synthesis above breakdown. Muscle growth is regulated by signal transduction pathways that sense and compute local and systemic signals and regulate various cellular functions. The main signalling mechanisms are the phosphorylation of serine, threonine and tyrosine residues by kinases and their dephosphorylation by phosphatases. Muscle growth is stimulated by the mTOR (mammalian target of rapamycin) system, which senses (i) IGF-1 (insulin-like growth factor 1)/MGF (mechano-growth factor)/insulin and/or (ii) mechanical signals, (iii) amino acids and (iv) the energetic state of the muscle, and regulates protein synthesis accordingly. The action of the mTOR system is opposed by myostatin-Smad signalling which inhibits muscle growth via gene transcription.

COLLAGEN AND NON–COLLAGEN PROTEIN TURNOVER IN SKELETAL MUSCLE OF GROWTH HORMONE–TREATED LAMBS

1987 ◽  
Vol 115 (1) ◽  
pp. R1-R4 ◽  
Author(s):  
J. M. Pell ◽  
P. C. Bates
Keyword(s):  
Protein Synthesis ◽  
Protein Turnover ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Gh Treatment ◽  
Collagen Protein ◽  
Red Muscle ◽  
Term Administration ◽  
Synthetic Capacity

ABSTRACT Long–term administration of GH to normal, well–fed lambs caused a significant increase in net muscle growth. This could be accounted for by increased rates of muscle protein synthesis, although red and white muscles responded differently. The increased rate of protein synthesis was due to an increased protein synthetic capacity (increased muscle RNA content) but efficiency per unit of RNA also tended to increase in red muscle. For similar increases in net growth, protein turnover was increased to a much greater extent in red than in white muscle. The ratio of collagen to non–collagen protein was unaffected in both muscle types by GH treatment, even though collagen synthesis rates were significantly increased in red muscle. To date, GH is the only anabolic agent in ruminants which acts via increased rates of protein synthesis rather than by decreased rates of protein degradation.

scholarly journals Circadian regulation of muscle growth independent of locomotor activity

2019 ◽  
Author(s):  
Jeffrey J. Kelu ◽  
Tapan G. Pipalia ◽  
Simon M. Hughes
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Contractile Activity ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Circadian Variation ◽  
Similar Extent ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation ◽  
Proteasomal Inhibitor

AbstractMuscle tissue shows circadian variation, but whether and how the intracellular circadian clock per se regulates muscle growth remains unclear. By measuring muscle growth over 12 h periods, here we show that muscle grows more during the day than at night. Inhibition of muscle contraction reduces growth to a similar extent in day and night, but does not ablate the circadian variation in growth. Muscle protein synthesis is higher during the day compared to night, whereas markers of protein degradation are higher at night. Mechanistically, the TORC1 inhibitor rapamycin inhibits the extra daytime growth, but no effect on muscle growth at night was detected. Conversely, the proteasomal inhibitor MG132 increases muscle growth at night, but has no effect during the day, irrespective of activity. Ablation of contractile activity rapidly reduces muscle protein synthesis both during the day and at night and leads to a gradual increase in Murf gene expression without ablating circadian variation in growth. Removal of circadian input by exposure to either permanent light or permanent darkness reduces muscle growth. We conclude that circadian variation in muscle growth is independent of the presence of, or changes in, physical activity and affects both protein synthesis and degradation in distinct circadian phases.

Precursor pools of protein synthesis: a stable isotope study in a swine model

1994 ◽  
Vol 267 (2) ◽  
pp. E203-E209 ◽  
Author(s):  
P. Q. Baumann ◽  
W. S. Stirewalt ◽  
B. D. O'Rourke ◽  
D. Howard ◽  
K. S. Nair
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Linear Regression Analysis ◽  
Swine Model ◽  
Tissue Fluid ◽  
Miniature Swine ◽  
Plasma Phenylalanine ◽  
Tissue Protein Synthesis ◽  
Stable Isotope Study

The accuracy of using other free pools in lieu of tRNA for calculation of tissue protein synthesis in liver (L), skeletal muscle (SM), and heart (H) was assessed in six adult miniature swine using L-[1-13C]leucine and L-[ring-2H5]phenylalanine as tracers. L leucyl-tRNA enrichment was higher than arterial plasma leucine and ketoisocaproate (KIC) enrichments, and L phenylalanyl-tRNA enrichment was higher than arterial phenylalanine enrichment (P < 0.05). No such differences were noted in SM and H. Leucyl- and phenylalanyl-tRNA enrichments in L were best predicted by the respective amino acid enrichments in tissue fluid [TF; Leu: slope (m) = 0.954 +/- 0.035; Phe: m = 1.011 +/- 0.032] using linear regression analysis to determine the accuracy of the prediction, whereas plasma phenylalanine reasonably predicted phenylalanyl-tRNA (artery: m = 0.821 +/- 0.032; vein: m = 0.947 +/- 0.135). In SM, plasma KIC (artery: m = 0.846 +/- 0.046; vein: m = 0.881 +/- 0.043) and TF leucine (m = 0.788 +/- 0.034) predicted leucyl-tRNA with high accuracy. In H tissue, TF (m = 0.991 +/- 0.044) was the best predictor of leucyl-tRNA enrichment, whereas arterial phenylalanine (m = 0.912 +/- 0.015) was the most reliable predictor of phenylalanyl-tRNA enrichment. The relationships between aminoacyl-tRNA and other free pools in the same species under the same study conditions differ in different tissues. Use of KIC in lieu of leucyl-tRNA for calculating muscle protein synthesis is supported by this study.

scholarly journals Does habitual dietary intake influence myofiber hypertrophy in response to resistance training? A cluster analysis

2009 ◽  
Vol 34 (4) ◽  
pp. 632-639 ◽  
Author(s):  
Anna E. Thalacker-Mercer ◽  
John K. Petrella ◽  
Marcas M. Bamman
Keyword(s):  
Cluster Analysis ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Vastus Lateralis ◽  
Muscle Growth ◽  
Daily Intake ◽  
Dietary Recommendations ◽  
Extrinsic Factors ◽  
Cross Sectional

Although resistance exercise training (RT) is a common intervention to stimulate muscle protein synthesis and increase skeletal muscle mass, the optimal daily protein and total energy intakes sufficient to support RT-mediated muscle growth are as yet unclear. Further, the efficacy of RT varies widely among adults of all ages and whether this is attributable to interindividual differences in nutrition is not known. To determine if self-selected daily intake of macronutrients and specific components of dietary protein and fat are predictive of the magnitude of RT-mediated muscle growth, detailed 4-day dietary records were analyzed on 60 subjects previously clustered (K-means cluster analysis) as non-, modest, and extreme responders (non, n = 16; mod, n = 29; xtr, n = 15), based on the magnitudes of change in vastus lateralis myofiber cross-sectional area following a 16-week, 3-day-per-week, high-intensity RT. Despite the marked contrast between 60% myofiber hypertrophy in xtr and zero growth in non, we found no differences among response clusters in daily intakes of energy (mean ± SEM: non 102 ± 8; mod 111 ± 6; xtr 109 ± 5 kJ·kg–1·day–1), protein (non 0.97 ± 0.08; mod 1.07 ± 0.07; xtr 1.05 ± 0.06 g·kg–1·day–1), carbohydrate (non 3.02 ± 0.24; mod 3.18 ± 0.20; xtr 3.14 ± 0.17 g·kg–1·day–1), and fat (non 0.95 ± 0.09; mod 1.05 ± 0.08; xtr 1.03 ± 0.08 g·kg–1·day–1), which generally met or exceeded dietary recommendations. There were no cluster differences in intakes of branched chain amino acids known to stimulate muscle protein synthesis. Using the novel K-means clustering approach, we conclude from this preliminary study that protein and energy intakes were sufficient to facilitate modest and extreme muscle growth during RT and intrinsic or extrinsic factors other than nutrient ingestion apparently impaired the anabolic response in nonresponders.

scholarly journals Expression of growth-related genes in young and older human skeletal muscle following an acute stimulation of protein synthesis

2009 ◽  
Vol 106 (4) ◽  
pp. 1403-1411 ◽  
Author(s):  
Micah J. Drummond ◽  
Mitsunori Miyazaki ◽  
Hans C. Dreyer ◽  
Bart Pennings ◽  
Shaheen Dhanani ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Human Skeletal Muscle ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Age Groups ◽  
Essential Amino Acids ◽  
Exercise Muscle

Muscle growth is associated with an activation of the mTOR signaling pathway and satellite cell regulators. The purpose of this study was to determine whether 17 selected genes associated with mTOR/muscle protein synthesis and the satellite cells/myogenic program are differentially expressed in young and older human skeletal muscle at rest and in response to a potent anabolic stimulus [resistance exercise + essential amino acid ingestion (RE+EAA)]. Twelve male subjects (6 young, 6 old) completed a bout of heavy resistance exercise. Muscle biopsies were obtained before and at 3 and 6 h post RE+EAA. Subjects ingested leucine-enriched essential amino acids at 1 h postexercise. mRNA expression was determined using qRT-PCR. At rest, hVps34 mRNA was elevated in the older subjects ( P < 0.05) while there was a tendency for levels of myoD, myogenin, and TSC2 mRNA to be higher than young. The anabolic stimulus (RE+EAA) altered mRNAs associated with mTOR regulation. Notably, REDD2 decreased in both age groups ( P < 0.05) but the expression of Rheb mRNA increased only in the young. Finally, cMyc mRNA was elevated ( P < 0.05) in both young and old at 6 h post RE+EAA. Furthermore, RE+EAA also increased expression of several mRNAs associated with satellite function in the young ( P < 0.05), while expression of these mRNAs did not change in the old. We conclude that several anabolic genes in muscle are more responsive in young men post RE+EAA. Our data provide new insights into the regulation of genes important for transcription and translation in young and old human skeletal muscle post RE+EAA.

Effects of the anabolic steroid stanozolol on growth and protein metabolism in the rat

1987 ◽  
Vol 114 (3) ◽  
pp. 373-381 ◽  
Author(s):  
P. C. Bates ◽  
L. F. Chew ◽  
D. J. Millward
Keyword(s):  
Protein Synthesis ◽  
Anabolic Steroid ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Female Rats ◽  
Male Rats ◽  
Anabolic Action ◽  
Rna Concentration

ABSTRACT The effects of the anabolic steroid stanozolol on whole body and muscle growth and protein metabolism in the rat have been examined. No responses could be found in normal well-fed male rats. Female rats responded to 1 mg/kg per day with an increased body and skeletal muscle growth rate and an increase in muscle protein synthesis. The anabolic action on muscle protein synthesis was due to increased RNA concentration with no change in the rate of protein synthesis per unit RNA (KRNA). Investigation of any anticatabolic effects of stanozolol treatment in male rats deprived of food for 24 h indicated no response of protein balance and turnover. However, rats treated with catabolic doses of corticosterone (50 mg/kg per day) did respond to stanozolol with decreased muscle growth inhibition due to better-maintained muscle protein synthesis. The latter response was due to a reversal of the corticosterone-induced reduction of KRNA, but with no effect on RNA concentration. Thus there appear to be at least two effects of stanozolol; an anabolic action evident only in female rats, involving increased muscle RNA concentrations, and an anticatabolic action involving inhibition of the corticosterone-induced fall in muscle RNA activity. In both cases, stanozolol influenced muscle protein synthesis with no evident effects on protein degradation. J. Endocr. (1987) 114, 373–381

Bigger weights may not beget bigger muscles: evidence from acute muscle protein synthetic responses after resistance exercise

2012 ◽  
Vol 37 (3) ◽  
pp. 551-554 ◽  
Author(s):  
Nicholas A. Burd ◽  
Cameron J. Mitchell ◽  
Tyler A. Churchward-Venne ◽  
Stuart M. Phillips
Keyword(s):  
Protein Synthesis ◽  
Resistance Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Growth ◽  
Exercise Recovery ◽  
Maximal Strength ◽  
Volitional Fatigue ◽  
Exercise Induced ◽  
Induced Changes

It is often recommended that heavier training intensities (∼70%–80% of maximal strength) be lifted to maximize muscle growth. However, we have reported that intensities as low as 30% of maximum strength, when lifted to volitional fatigue, are equally effective at stimulating muscle protein synthesis rates during resistance exercise recovery. This paper discusses the idea that high-intensity contractions are not the exclusive driver of resistance exercise-induced changes in muscle protein synthesis rates.

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