scholarly journals LOW-INTENSITY EXERCISE ENHANCES MUSCULAR ANDROGEN/ANDROGEN RECEPTOR TO INHIBIT MYOSTATIN PATHWAY

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S85-S86
Author(s):  
Bo-Kyung Son ◽  
Masato Eto ◽  
Miya Oura ◽  
Masahiro Akishita
Keyword(s):  
Skeletal Muscle ◽  
Androgen Receptor ◽  
Electric Pulse ◽  
Negative Regulator ◽  
Muscle Size ◽  
C2c12 Myotubes ◽  
Protein Levels ◽  
Low Intensity ◽  
Low Intensity Exercise ◽  
Response To Exercise

Abstract Background: Physical exercise is well documented to induce muscle size, strength, and energy metabolism. Although the contribution of systemic or local androgen in exercise-adapted muscle hypertrophy has been suggested, less is known about the molecular pathway of androgen in response to exercise. In the present study, we examined roles of androgen/androgen receptor (AR) after exercise, especially for the suppression of myostatin, a potent negative regulator of muscle mass. Methods and Results: To examine the effects of exercise, we employed low-intensity exercise in mice and electric pulse stimulation (EPS) in C2C12 myotubes. Both mRNA and protein levels of AR significantly increased in skeletal muscle of low-intensity exercised mice and C2C12 myotubes exposed to EPS. Production of testosterone and DHT from EPS-treated C2C12 myotubes was markedly increased. Of interest, we found that myostatin was clearly inhibited by EPS, and its inhibition was significantly abrogated by flutamide, a specific antagonist of AR. Furthermore, IL-6 and phospho-STAT3 (pSTAT3) expression, the downstream pathway of myostatin, were decreased by EPS and this was also reversed by flutamide. Similar downregulation of myostatin and IL-6 was seen in skeletal muscle of low-intensity exercised mice. Conclusion: Muscle AR expression and androgen production were increased by exercise and EPS treatment. As a mechanistical insight, it is suggested that AR inhibited myostatin expression transcriptionally, which downregulates IL-6/pSTAT3 pathway and thus contributes to the prevention of muscle degradation.

scholarly journals An AMPK/Axin1-Rac1 signaling pathway mediates contraction-regulated glucose uptake in skeletal muscle cells

2020 ◽  
Vol 318 (3) ◽  
pp. E330-E342 ◽  
Author(s):  
Yingying Yue ◽  
Chang Zhang ◽  
Xuejiao Zhang ◽  
Shitian Zhang ◽  
Qian Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Gastrocnemius Muscle ◽  
C2c12 Myotubes ◽  
Dependent Manner ◽  
Mouse Muscle ◽  
Protein Levels ◽  
Compound C ◽  
Skeletal Muscle Glucose Uptake

Contraction stimulates skeletal muscle glucose uptake predominantly through activation of AMP-activated protein kinase (AMPK) and Rac1. However, the molecular details of how contraction activates these signaling proteins are not clear. Recently, Axin1 has been shown to form a complex with AMPK and liver kinase B1 during glucose starvation-dependent activation of AMPK. Here, we demonstrate that electrical pulse-stimulated (EPS) contraction of C2C12 myotubes or treadmill exercise of C57BL/6 mice enhanced reciprocal coimmunoprecipitation of Axin1 and AMPK from myotube lysates or gastrocnemius muscle tissue. Interestingly, EPS or exercise upregulated total cellular Axin1 levels in an AMPK-dependent manner in C2C12 myotubes and gastrocnemius mouse muscle, respectively. Also, direct activation of AMPK with 5-aminoimidazole-4-carboxamide ribonucleotide treatment of C2C12 myotubes or gastrocnemius muscle elevated Axin1 protein levels. On the other hand, siRNA-mediated Axin1 knockdown lessened activation of AMPK in contracted myotubes. Further, AMPK inhibition with compound C or siRNA-mediated knockdown of AMPK or Axin1 blocked contraction-induced GTP loading of Rac1, p21-activated kinase phosphorylation, and contraction-stimulated glucose uptake. In summary, our results suggest that an AMPK/Axin1-Rac1 signaling pathway mediates contraction-stimulated skeletal muscle glucose uptake.

scholarly journals Defining the contribution of skeletal muscle pyruvate dehydrogenase α1 to exercise performance and insulin action

2018 ◽  
Vol 315 (5) ◽  
pp. E1034-E1045 ◽  
Author(s):  
Kristoffer Svensson ◽  
Jessica R. Dent ◽  
Shahriar Tahvilian ◽  
Vitor F. Martins ◽  
Abha Sathe ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Energy Expenditure ◽  
Exercise Performance ◽  
Pyruvate Dehydrogenase ◽  
High Intensity ◽  
High Intensity Exercise ◽  
Low Intensity ◽  
Low Intensity Exercise ◽  
Muscle Contractile

The pyruvate dehydrogenase complex (PDC) converts pyruvate to acetyl-CoA and is an important control point for carbohydrate (CHO) oxidation. However, the importance of the PDC and CHO oxidation to muscle metabolism and exercise performance, particularly during prolonged or high-intensity exercise, has not been fully defined especially in mature skeletal muscle. To this end, we determined whether skeletal muscle-specific loss of pyruvate dehydrogenase alpha 1 ( Pdha1), which is a critical subunit of the PDC, impacts resting energy metabolism, exercise performance, or metabolic adaptation to high-fat diet (HFD) feeding. For this, we generated a tamoxifen (TMX)-inducible Pdha1 knockout (PDHmKO) mouse, in which PDC activity is temporally and specifically ablated in adult skeletal muscle. We assessed energy expenditure, ex vivo muscle contractile performance, and endurance exercise capacity in PDHmKO mice and wild-type (WT) littermates. Additionally, we studied glucose homeostasis and insulin sensitivity in muscle after 12 wk of HFD feeding. TMX administration largely ablated PDHα in skeletal muscle of adult PDHmKO mice but did not impact energy expenditure, muscle contractile function, or low-intensity exercise performance. Additionally, there were no differences in muscle insulin sensitivity or body composition in PDHmKO mice fed a control or HFD, as compared with WT mice. However, exercise capacity during high-intensity exercise was severely impaired in PDHmKO mice, in parallel with a large increase in plasma lactate concentration. In conclusion, although skeletal muscle PDC is not a major contributor to resting energy expenditure or long-duration, low-intensity exercise performance, it is necessary for optimal performance during high-intensity exercise.

scholarly journals REDD2 is enriched in skeletal muscle and inhibits mTOR signaling in response to leucine and stretch

2009 ◽  
Vol 296 (3) ◽  
pp. C583-C592 ◽  
Author(s):  
Mitsunori Miyazaki ◽  
Karyn A. Esser
Keyword(s):  
Skeletal Muscle ◽  
Mammalian Target Of Rapamycin ◽  
Mechanical Stretch ◽  
Mtor Signaling ◽  
Negative Regulator ◽  
Muscle Size ◽  
Inhibitory Function ◽  
Dna Damage Responses ◽  
Si Rna ◽  
Mtor Activity

The protein kinase mammalian target of rapamycin (mTOR) is well established as a key regulator of skeletal muscle size. In this study, we determined that the stress responsive gene REDD2 (regulated in development and DNA damage responses 2) is a negative regulator of mTOR signaling and is expressed predominantly in skeletal muscle. Overexpression of REDD2 in muscle cells significantly inhibited basal mTOR signaling and diminished the response of mTOR to leucine addition or mechanical stretch. The inhibitory function of REDD2 on mTOR signaling seems to be mediated downstream or independent of Akt signaling and upstream of Rheb (Ras homolog enriched in brain). Knock down of tuberous sclerosis complex 2 (TSC2) using small interfering (si)RNA potently activated mTOR signaling and was sufficient to rescue REDD2 inhibition of mTOR activity, suggesting that REDD2 functions by modulating TSC2 function. Immunoprecipitation assays demonstrated that REDD2 does not directly interact with either TSC1 or TSC2. However, we found that REDD2 forms a complex with 14-3-3 protein and that increasing expression of REDD2 acts to competitively dissociate TSC2 from 14-3-3 and inhibits mTOR signaling. These findings demonstrate that REDD2 is a skeletal muscle specific inhibitory modulator of mTOR signaling and identify TSC2 and 14-3-3 as key molecular links between REDD2 and mTOR function.

Effects of physical exercise on phospholipid fatty acid composition in skeletal muscle

1998 ◽  
Vol 274 (3) ◽  
pp. E432-E438 ◽  
Author(s):  
Agneta Andersson ◽  
Anders Sjödin ◽  
Roger Olsson ◽  
Bengt Vessby
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Acid Composition ◽  
The Body ◽  
Muscle Membrane ◽  
Peripheral Insulin Sensitivity ◽  
Low Intensity ◽  
Low Intensity Exercise

The effects of low-intensity exercise on the fatty acid composition in skeletal muscle and in serum were studied in 19 sedentary, middle-aged Swedish men. During a 10-wk period, all subjects were given a standardized diet with an identical fat composition. After 4 wk on this diet, they were randomly allocated to a daily exercise program (55% peak oxygen uptake) or to continue to live a sedentary life for the remaining 6 wk. Aerobic capacity (submaximal bicycle test) and peripheral insulin sensitivity (hyperinsulinemic euglycemic clamp) improved with training, whereas the body weight as well as the body composition (underwater weighing and bioimpedance) were unchanged. The proportions of palmitic acid (16:0) and linoleic acid [18:2(n-6)] and the sum of n-6 fatty acids [18:2(n-6), 20:3(n-6), 20:4(n-6)] were decreased in skeletal muscle phospholipids, whereas the proportion of oleic acid [18:1(n-9)] was increased, by training. The fatty acid profile in skeletal muscle triglycerides remained unchanged. We conclude that regular low-intensity exercise influences the fatty acid composition of the phospholipids in skeletal muscle, which hypothetically may contribute to changes of the skeletal muscle membrane fluidity and influence the peripheral insulin sensitivity.

scholarly journals Myostatin inhibits IGF-I-induced myotube hypertrophy through Akt

2009 ◽  
Vol 297 (5) ◽  
pp. 1124-1132 ◽  
Author(s):  
Michael R. Morissette ◽  
Stuart A. Cook ◽  
Cattleya Buranasombati ◽  
Michael A. Rosenberg ◽  
Anthony Rosenzweig
Keyword(s):  
Skeletal Muscle ◽  
Knockout Mice ◽  
Molecular Mechanisms ◽  
Muscle Growth ◽  
Dominant Negative ◽  
Negative Regulator ◽  
C2c12 Myotubes ◽  
Akt Phosphorylation ◽  
Igf I

Myostatin is a highly conserved negative regulator of skeletal muscle growth. Loss of functional myostatin in cattle, mice, sheep, dogs, and humans results in increased muscle mass. The molecular mechanisms responsible for this increase in muscle growth are not fully understood. Previously, we have reported that phenylephrine-induced cardiac muscle growth and Akt activation are enhanced in myostatin knockout mice compared with controls. Here we report that skeletal muscle from myostatin knockout mice show increased Akt protein expression and overall activity at baseline secondary to an increase in Akt mRNA. We examined the functional role of myostatin modulation of Akt in C2C12 myotubes, a well-established in vitro model of skeletal muscle hypertrophy. Adenoviral overexpression of myostatin attenuated the insulin-like growth factor-I (IGF-I)-mediated increase in myotube diameter, as well as IGF-I-stimulated Akt phosphorylation. Inhibition of myostatin by overexpression of the NH2-terminal portion of myostatin was sufficient to increase myotube diameter and Akt phosphorylation. Coexpression of myostatin and constitutively active Akt (myr-Akt) restored the increase in myotube diameter. Conversely, expression of dominant negative Akt (dn-Akt) with the inhibitory myostatin propeptide blocked the increase in myotube diameter. Of note, ribosomal protein S6 phosphorylation and atrogin-1/muscle atrophy F box mRNA were increased in skeletal muscle from myostain knockout mice. Together, these data suggest myostatin regulates muscle growth at least in part through regulation of Akt.

Low-Intensity Exercise Suppresses CCAAT/Enhancer-Binding Protein δ/Myostatin Pathway Through Androgen Receptor in Muscle Cells

Gerontology ◽  
2019 ◽  
Vol 65 (4) ◽  
pp. 397-406
Author(s):  
Bo-Kyung Son ◽  
Masato Eto ◽  
Miya Oura ◽  
Yuki Ishida ◽  
Sakiko Taniguchi ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Binding Protein ◽  
Muscle Cells ◽  
Low Intensity ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Low Intensity Exercise
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