scholarly journals Syncytin-1 Expression is Increased in Skeletal Muscle of Humans with Obesity and is Inversely Correlated to Muscle Protein Synthesis

2021 ◽  
Author(s):  
Jayachandran Ravichandran ◽  
Lori R Roust ◽  
Christos Katsanos
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
C2c12 Cell ◽  
C2c12 Cells ◽  
Anabolic Hormone ◽  
Lower Protein ◽  
Potential Link

Abstract Background: Various pathophysiological conditions alter protein metabolism in skeletal muscle, with obesity being one of them. Obesity impairs regeneration of skeletal muscle, and the same biological mechanism(s) may adversely affect protein metabolism in the muscle of these individuals. Methods: We used C2C12 cell line to evaluate the effects of the anabolic hormone insulin on the expression of protein syncytin-1, which regulates regeneration of muscle, and in the presence of fatty acids whose metabolism is altered in obesity. We used muscle biopsy samples from obese humans with lower muscle protein synthesis and lean controls to evaluate expression of syncytin-1 in obesity and its correlation with protein synthesis in muscle. Results: Insulin upregulated syncytin-1 expression in C2C12 cells and this response was impaired in the presence of the fatty acid palmitate, but not oleate. Expression of the protein 4E-BP1, which signals increase in protein synthesis in muscle, showed response similar to that of syncytin-1. Humans with obesity characterized by lower muscle protein synthesis had higher expression of syncytin-1 in muscle compared to lean humans (P < 0.01). The rate of synthesis of protein in skeletal muscle across humans subjects correlated inversely (r = -0.51; P = 0.03) with the expression of syncytin-1 in muscle. Conclusions: Our studies provide novel insights in the regulation of syncytin-1 in skeletal muscle, and describe potential link between syncytin-1 expression and protein metabolism in skeletal muscle of humans. Altered syncytin-1 expression in muscle may mediate lower protein turnover in muscle of humans with obesity.

scholarly journals Notch Inhibition via GSI Treatment Elevates Protein Synthesis in C2C12 Myotubes

Biology ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 115
Author(s):  
Joshua R. Huot ◽  
Joseph S. Marino ◽  
Michael J. Turner ◽  
Susan T. Arthur
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Notch Signaling ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
C2c12 Cells ◽  
Skeletal Muscle Regeneration ◽  
C2c12 Myotubes ◽  
Myonuclear Domain ◽  
Myotube Hypertrophy

The role of Notch signaling is widely studied in skeletal muscle regeneration but little is known about its influences on muscle protein synthesis (MPS). The purpose of this study was to investigate whether Notch signaling is involved in the regulation of MPS. C2C12 cells were treated with a γ-secretase inhibitor (GSI), to determine the effect of reduced Notch signaling on MPS and anabolic signaling markers. GSI treatment increased myotube hypertrophy by increasing myonuclear accretion (nuclei/myotube: p = 0.01) and myonuclear domain (myotube area per fusing nuclei: p < 0.001) in differentiating C2C12 cells. GSI treatment also elevated myotube hypertrophy in differentiated C2C12s (area/myotube; p = 0.01). In concert, GSI treatment augmented pmTOR Ser2448 (p = 0.01) and protein synthesis (using SUnSET method) in myotubes (p < 0.001). Examining protein expression upstream of mTOR revealed reductions in PTEN (p = 0.04), with subsequent elevations in pAKT Thr308 (p < 0.001) and pAKT Ser473 (p = 0.05). These findings reveal that GSI treatment elevates myotube hypertrophy through both augmentation of fusion and MPS. This study sheds light on the potential multifaceted roles of Notch within skeletal muscle. Furthermore, we have demonstrated that Notch may modulate the PTEN/AKT/mTOR pathway.

scholarly journals Phenotypic regulation of animal skeletal muscle protein metabolism

2019 ◽  
Vol 9 (4) ◽  
pp. 651-656 ◽  
Author(s):  
K. T. Erimbetov ◽  
O. V. Obvintseva ◽  
A. V. Fedorova ◽  
R. A. Zemlyanoy ◽  
A. G. Solovieva
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Signaling Pathways ◽  
Muscle Mass ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mrna Translation ◽  
Mtorc1 Signaling ◽  
Muscle Protein Metabolism

This review highlights the current state of phenotypic mechanisms of regulation of muscle protein metabolism in animals. Since the skeletal muscle represents 40–50% of body mass in mammals it is a critical regulator of overall metabolism. Therefore, an understanding of the processes involved in the postnatal increase in muscle mass, with associated accumulation of protein, is fundamental. Throughout life, a delicate balance exists between protein synthesis and degradation that is essential for growth and normal health of humans and animals. Signaling pathways coordinate muscle protein balance. Anabolic and catabolic stimuli are integrated through the PKB/Akt-mTORC1 signaling to regulate mechanisms that control muscle protein synthesis and breakdown. At an early periods of intensive growth, muscle mass is stimulated by an increase in protein synthesis at the level of mRNA translation. Throughout the life, proteolytic processes including autophagy lysosomal system, ubiquitin proteasome pathway, calcium-dependent calpains and cysteine protease caspase enzyme cascade influence the growth of muscle mass. Several signal transmission networks direct and coordinate these processes along with quality control mechanisms to maintain protein homeostasis (proteostasis). Genetic factors, hormones, amino acids, phytoecdysteroids, and rhodanines affect the protein metabolism via signaling pathways, changing the ability and / or efficiency of muscle growth.

Chronic α-tocopherol supplementation in rats does not ameliorate either chronic or acute alcohol-induced changes in muscle protein metabolism

2003 ◽  
Vol 104 (3) ◽  
pp. 287-294 ◽  
Author(s):  
Michael KOLL ◽  
Julie A. BEESO ◽  
Frank J. KELLY ◽  
Ulrich A. SIMANOWSKI ◽  
Helmut K. SEITZ ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Content ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Muscle Disease ◽  
Plantaris Muscle ◽  
Dna Contents ◽  
Rna And Dna

Chronic alcohol muscle disease is characterized by reduced skeletal muscle mass precipitated by acute reduction in protein synthesis. The pathogenic mechanisms remain obscure, but several lines of evidence suggest that increased oxidative stress occurs in muscle in response to alcohol and this may be associated with impaired α-tocopherol status. Potentially, this implies a therapeutic role for α-tocopherol, especially as we have shown that supplemental α-tocopherol may increase the rate of protein synthesis in normal rats [Reilly, Patel, Peters and Preedy (2000) J. Nutr. 130, 3045–3049]. We investigated the therapeutic effect of α-tocopherol on plantaris muscle protein synthesis in rats treated either acutely, chronically or chronically+acutely with ethanol. Protein synthesis rates were measured with a flooding dose of L-[4-3H]phenylalanine. Protein, RNA and DNA contents were determined by standard laboratory methods. Ethanol caused defined metabolic changes in muscle, including decreased protein, RNA and DNA contents in chronically treated rats. In acute or chronic+acute studies, ethanol suppressed fractional rates of protein synthesis. α-Tocopherol supplementation did not ameliorate the effects of either acute, chronic or chronic+acute alcohol on plantaris muscle protein content or rates of protein synthesis. In control animals (not treated with alcohol), α-tocopherol supplementation decreased muscle protein content owing to increases in protein turnover (both synthesis and degradation). α-Tocopherol supplementation is not protective against the deleterious effects of alcohol on protein metabolism in skeletal muscle.

Adaptation to prolonged starvation in the rat: curtailment of skeletal muscle proteolysis

1981 ◽  
Vol 241 (4) ◽  
pp. E321-E327 ◽  
Author(s):  
M. N. Goodman ◽  
M. A. McElaney ◽  
N. B. Ruderman
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Early Event ◽  
Body Protein ◽  
Fed State ◽  
Prolonged Starvation ◽  
Obese Rats ◽  
Old Rats

Previous studies have established that 16-wk-old nonobese and obese rats conserve body protein during prolonged starvation. To determine the basis for this, protein synthesis and degradation in skeletal muscle were evaluated in the isolated perfused hindquarters of these rats, in the fed state and when starved for 2, 5, 10, and 11 days. Rats aged 4 and 8 wk were used as a comparison. The results indicate that the response to starvation depends on several factors: the age of the rat, its degree of adiposity, and the duration of the fast. An early event in starvation was a decline in muscle protein synthesis. This occurred in all groups, albeit this reduction occurred more slowly in the older rats. A later response to starvation was an increase in muscle proteolysis. This occurred between 2 and 5 days in the 8-wk-old rats. In 16-wk-old rats it did not occur until between 5 and 10 days, and it was preceded by a period of decreased proteolysis. In 16-wk-old obese rats, a decrease in proteolysis persisted for upwards of 10 days and the secondary increase was not noted during the period of study. The data suggest that the ability of older and more obese rats to conserve body protein during starvation is due, in part, to a curtailment of muscle proteolysis. This adaptation seems to correlate with the availability of lipid fuels.

scholarly journals Resistance exercise maintains skeletal muscle protein synthesis during bed rest

1997 ◽  
Vol 82 (3) ◽  
pp. 807-810 ◽  
Author(s):  
Arny A. Ferrando ◽  
Kevin D. Tipton ◽  
Marcas M. Bamman ◽  
Robert R. Wolfe
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Resistance Training ◽  
Resistance Exercise ◽  
Lean Body Mass ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Bed Rest ◽  
Skeletal Muscle Protein ◽  
Skeletal Muscle Protein Synthesis

Ferrando, Arny A., Kevin D. Tipton, Marcas M. Bamman, and Robert R. Wolfe. Resistance exercise maintains skeletal muscle protein synthesis during bed rest. J. Appl. Physiol. 82(3): 807–810, 1997.—Spaceflight results in a loss of lean body mass and muscular strength. A ground-based model for microgravity, bed rest, results in a loss of lean body mass due to a decrease in muscle protein synthesis (MPS). Resistance training is suggested as a proposed countermeasure for spaceflight-induced atrophy because it is known to increase both MPS and skeletal muscle strength. We therefore hypothesized that scheduled resistance training throughout bed rest would ameliorate the decrease in MPS. Two groups of healthy volunteers were studied during 14 days of simulated microgravity. One group adhered to strict bed rest (BR; n = 5), whereas a second group engaged in leg resistance exercise every other day throughout bed rest (BREx; n = 6). MPS was determined directly by the incorporation of infusedl-[ ring-13C6]phenylalanine into vastus lateralis protein. After 14 days of bed rest, MPS in the BREx group did not change and was significantly greater than in the BR group. Thus moderate-resistance exercise can counteract the decrease in MPS during bed rest.

Growth hormone acutely stimulates forearm muscle protein synthesis in normal humans

1991 ◽  
Vol 260 (3) ◽  
pp. E499-E504 ◽  
Author(s):  
D. A. Fryburg ◽  
R. A. Gelfand ◽  
E. J. Barrett
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Growth Hormone ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Skeletal Muscle Protein ◽  
Skeletal Muscle Protein Synthesis ◽  
Igf I ◽  
Normal Humans

The short-term effects of growth hormone (GH) on skeletal muscle protein synthesis and degradation in normal humans are unknown. We studied seven postabsorptive healthy men (age 18-23 yr) who received GH (0.014 micrograms.kg-1.min-1) via intrabrachial artery infusion for 6 h. The effects of GH on forearm amino acid and glucose balances and on forearm amino acid kinetics [( 3H]Phe and [14C]Leu) were determined after 3 and 6 h of the GH infusion. Forearm deep vein GH rose to 35 +/- 6 ng/ml in response to GH, whereas systemic levels of GH, insulin, and insulin-like growth factor I (IGF-I) were unchanged. Forearm glucose uptake did not change during the study. After 6 h, GH suppressed forearm net release (3 vs. 6 h) of Phe (P less than 0.05), Leu (P less than 0.01), total branched-chain amino acids (P less than 0.025), and essential neutral amino acids (0.05 less than P less than 0.1). The effect on the net balance of Phe and Leu was due to an increase in the tissue uptake for Phe (71%, P less than 0.05) and Leu (37%, P less than 0.005) in the absence of any significant change in release of Phe or Leu from tissue. In the absence of any change in systemic GH, IGF-I, or insulin, these findings suggest that locally infused GH stimulates skeletal muscle protein synthesis. These findings have important physiological implications for both the role of daily GH pulses and the mechanisms through which GH can promote protein anabolism.

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