scholarly journals Effects of Rhizome Extract of Dioscorea batatas and Its Active Compound, Allantoin, on the Regulation of Myoblast Differentiation and Mitochondrial Biogenesis in C2C12 Myotubes

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 2023 ◽  
Author(s):  
Junnan Ma ◽  
Seok Yong Kang ◽  
Xianglong Meng ◽  
An Na Kang ◽  
Jong Hun Park ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Mitochondrial Biogenesis ◽  
Water Extract ◽  
Sirtuin 1 ◽  
Myoblast Differentiation ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dioscorea Batatas

With the aging process, a loss of skeletal muscle mass and dysfunction related to metabolic syndrome is observed in older people. Yams are commonly use in functional foods and medications with various effects. The present study was conducted to investigate the effects of rhizome extract of Dioscorea batatas (Dioscoreae Rhizoma, Chinese yam) and its bioactive compound, allantoin, on myoblast differentiation and mitochondrial biogenesis in skeletal muscle cells. Yams were extracted in water and allantoin was analyzed by high performance liquid chromatography (HPLC). The expression of myosin heavy chain (MyHC) and mitochondrial biogenesis-regulating factors, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), sirtuin-1 (Sirt-1), nuclear respiratory factor-1 (NRF-1) and transcription factor A, mitochondrial (TFAM), and the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) were determined in C2C12 myotubes by reverse transcriptase (RT)-polymerase chain reaction (RT-PCR) or western blot. The glucose levels and total ATP contents were measured by glucose consumption, glucose uptake and ATP assays, respectively. Treatment with yam extract (1 mg/mL) and allantoin (0.2 and 0.5 mM) significantly increased MyHC expression compared with non-treated myotubes. Yam extract and allantoin significantly increased the expression of PGC-1α, Sirt-1, NRF-1 and TFAM, as well as the phosphorylation of AMPK and ACC in C2C12 myotubes. Furthermore, yam extract and allantoin significantly increased glucose uptake levels and ATP contents. Finally, HPLC analysis revealed that the yam water extract contained 1.53% of allantoin. Yam extract and allantoin stimulated myoblast differentiation into myotubes and increased energy production through the upregulation of mitochondrial biogenesis regulators. These findings indicate that yam extract and allantoin can help to prevent skeletal muscle dysfunction through the stimulation of the energy metabolism.

scholarly journals Effects of Rhizome Extract of Dioscorea Batatas and Its Active Compound, Allantoin, on the Regulation of Myoblast Differentiation and Mitochondrial Biogenesis in C2C12 Myotubes

2018 ◽  
Author(s):  
Jun Nan Ma ◽  
Seok Yong Kang ◽  
Jong Hun Park ◽  
Yong-Ki Park ◽  
Hyo Won Jung
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Mitochondrial Biogenesis ◽  
Glucose Consumption ◽  
Bioactive Compound ◽  
Myoblast Differentiation ◽  
C2c12 Myotubes ◽  
Glucose Levels ◽  
Skeletal Muscle Dysfunction ◽  
Dioscorea Batatas

The present study was conducted to investigate the effects of rhizome extract of Dioscorea batatas (Dioscoreae Rhizoma, Chinese Yam) and its bioactive compound, allantoin, on myoblast differentiation and mitochondrial biogenesis in skeletal muscle cells. Yams were extracted in water and the extract was analyzed by HPLC. The expression of C2C12 myotubes differentiation and mitochondrial biogenesis regulators were determined by reverse transcriptase (RT)-PCR or Western blot. The glucose levels and total ATP contents were determined by glucose consumption, glucose uptake and ATP assays, respectively. Treatment with yam extract (1 mg/mL) and allantoin (0.2 and 0.5 mM) significantly increased of MyHC expression compared with non-treated myotubes. Yam extract and allantoin significantly increased the expression of mitochondrial biogenesis regulating proteins, PGC1?, Sirt-1, NRF-1, and TFAM, as well as the phosphorylation of AMPK and ACC in C2C12 myotubes. Furthermore, yam extract and allantoin significantly increased the glucose uptake levels and the ATP contents. Finally, HPLC analysis revealed that the yam extract contained 1.53% of allantoin. Yam extract and allantoin, stimulated myoblast differentiation into myotubes and increased energy production through upregulation of mitochondrial biogenesis regulators. These findings indicate that yam extract and allantoin can help to prevent the skeletal muscle dysfunction through stimulation of energy metabolism.

scholarly journals Mild heat stress induces mitochondrial biogenesis in C2C12 myotubes

2012 ◽  
Vol 112 (3) ◽  
pp. 354-361 ◽  
Author(s):  
Chien-Ting Liu ◽  
George A. Brooks
Keyword(s):  
Heat Stress ◽  
Mitochondrial Biogenesis ◽  
Atp Hydrolysis ◽  
Sirtuin 1 ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mild Heat ◽  
Beneficial Effects ◽  
Mitochondrial Dna Copy Number

During endurance exercise, most (≈75%) of the energy derived from the oxidation of metabolic fuels and ATP hydrolysis of muscle contraction is liberated as heat, the accumulation of which leads to an increase in body temperature. For example, the temperature of exercising muscles can rise to 40°C. Although severe heat injury can be deleterious, several beneficial effects of mild heat stress (HS), such as the improvement of insulin sensitivity in patients with type 2 diabetes, have been reported. However, among all cellular events induced by mild HS from physical activities, the direct effects and mechanisms of mild HS on mitochondrial biogenesis in skeletal muscle are least characterized. AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) are key energy-sensing molecules regulating mitochondrial biogenesis. In C2C12 myotubes, we found that 1 h mild HS at 40°C upregulated both AMPK activity and SIRT1 expression, as well as increased the expression of several mitochondrial biogenesis regulatory genes including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and transcription factors involved in mitochondrial biogenesis. In particular, PGC-1α expression was found to be transcriptionally regulated by mild HS. Additionally, after repeated mild HS for 5 days, protein levels of PGC-1α and several mitochondrial oxidative phosphorylation subunits were also upregulated. Repeated mild HS also significantly increased mitochondrial DNA copy number. In conclusion, these data show that mild HS is sufficient to induce mitochondrial biogenesis in C2C12 myotubes. Temperature-induced mitochondrial biogenesis correlates with activation of the AMPK-SIRT1-PGC-1α pathway. Therefore, it is possible that muscle heat production during exercise plays a role in mitochondrial biogenesis.

Effect of nitric oxide synthase inhibition on mitochondrial biogenesis in rat skeletal muscle

2007 ◽  
Vol 102 (1) ◽  
pp. 314-320 ◽  
Author(s):  
G. D. Wadley ◽  
G. K. McConell
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Mitochondrial Biogenesis ◽  
Acute Exercise ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Exercise Induced ◽  
Edl Muscle ◽  
Oxide Synthase

The purpose of this study was to determine whether nitric oxide synthase (NOS) inhibition decreased basal and exercise-induced skeletal muscle mitochondrial biogenesis. Male Sprague-Dawley rats were assigned to one of four treatment groups: NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME, ingested for 2 days in drinking water, 1 mg/ml) followed by acute exercise, no l-NAME ingestion and acute exercise, rest plus l-NAME, and rest without l-NAME. The exercised rats ran on a treadmill for 53 ± 2 min and were then killed 4 h later. NOS inhibition significantly ( P < 0.05; main effect) decreased basal peroxisome proliferator-activated receptor-γ coactivator 1β (PGC-1β) mRNA levels and tended ( P = 0.08) to decrease mtTFA mRNA levels in the soleus, but not the extensor digitorum longus (EDL) muscle. This coincided with significantly reduced basal levels of cytochrome c oxidase (COX) I and COX IV mRNA, COX IV protein and COX enzyme activity following NOS inhibition in the soleus, but not the EDL muscle. NOS inhibition had no effect on citrate synthase or β-hydroxyacyl CoA dehydrogenase activity, or cytochrome c protein abundance in the soleus or EDL. NOS inhibition did not reduce the exercise-induced increase in peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) mRNA in the soleus or EDL. In conclusion, inhibition of NOS appears to decrease some aspects of the mitochondrial respiratory chain in the soleus under basal conditions, but does not attenuate exercise-induced mitochondrial biogenesis in the soleus or in the EDL.

scholarly journals The Effect of Diet on Improved Endurance in Male C57BL/6 Mice

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1101 ◽  
Author(s):  
Jin Yu ◽  
Hong Zhu ◽  
Saeid Taheri ◽  
Stephen Perry ◽  
Mark Kindy
Keyword(s):  
Mitochondrial Biogenesis ◽  
Fruits And Vegetables ◽  
Sirtuin 1 ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Respiratory Factor ◽  
Mitochondrial Transcription Factor ◽  
Exercise Endurance ◽  
The Impact

The consumption of fruits and vegetables appears to help with maintaining an adequate level of exercise and improves endurance. However, the mechanisms that are involved in this process are not well understood. In the current study, the impact of diets enriched in fruits and vegetables (GrandFusion®) on exercise endurance was examined in a mouse model. GrandFusion (GF) diets increased mitochondrial DNA and enzyme activity, while they also stimulated mitochondrial mRNA synthesis in vivo. GF diets increased both the mRNA expression of factors involved in mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (Tfam), estrogen-related receptor alpha (ERRα), nuclear respiratory factor 1 (NRF-1), cytochrome c oxidase IV (COXIV) and ATP synthase (ATPsyn). Mice treated with GF diets showed an increase in running endurance, rotarod perseverance and grip strength when compared to controls who were on a regular diet. In addition, GF diets increased the protein expression of phosphorylated AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), PGC-1α and peroxisome proliferator-activated receptor delta (PPAR-δ), which was greater than exercise-related changes. Finally, GF reduced the expression of phosphorylated ribosomal protein S6 kinase 1 (p-S6K1) and decreased autophagy. These results demonstrate that GF diets enhance exercise endurance, which is mediated via mitochondrial biogenesis and function.

scholarly journals Metabolic regulation of exercise-induced angiogenesis

2019 ◽  
Vol 1 (1) ◽  
pp. H1-H8 ◽  
Author(s):  
Tatiane Gorski ◽  
Katrien De Bock
Keyword(s):  
Skeletal Muscle ◽  
Transcriptional Activation ◽  
Metabolic Regulation ◽  
Molecular Mechanisms ◽  
Metabolic Reprogramming ◽  
Sirtuin 1 ◽  
Peroxisome Proliferator ◽  
Valuable Insight ◽  
Peroxisome Proliferator Activated Receptor ◽  
Exercise Induced

Skeletal muscle relies on an ingenious network of blood vessels, which ensures optimal oxygen and nutrient supply. An increase in muscle vascularization is an early adaptive event to exercise training, but the cellular and molecular mechanisms underlying exercise-induced blood vessel formation are not completely clear. In this review, we provide a concise overview on how exercise-induced alterations in muscle metabolism can evoke metabolic changes in endothelial cells (ECs) that drive muscle angiogenesis. In skeletal muscle, angiogenesis can occur via sprouting and splitting angiogenesis and is dependent on vascular endothelial growth factor (VEGF) signaling. In the resting muscle, VEGF levels are controlled by the estrogen-related receptor γ (ERRγ). Upon exercise, the transcriptional coactivator peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC1α) orchestrates several adaptations to endurance exercise within muscle fibers and simultaneously promotes transcriptional activation of Vegf expression and increased muscle capillary density. While ECs are highly glycolytic and change their metabolism during sprouting angiogenesis in development and disease, a similar role for EC metabolism in exercise-induced angiogenesis in skeletal muscle remains to be elucidated. Nonetheless, recent studies have illustrated the importance of endothelial hydrogen sulfide and sirtuin 1 (SIRT1) activity for exercise-induced angiogenesis, suggesting that EC metabolic reprogramming may be fundamental in this process. We hypothesize that the exercise-induced angiogenic response can also be modulated by metabolic crosstalk between muscle and the endothelium. Defining the underlying molecular mechanisms responsible for skeletal muscle angiogenesis in response to exercise will yield valuable insight into metabolic regulation as well as the determinants of exercise performance.

scholarly journals Low-Frequency Electroacupuncture Improves Insulin Sensitivity in Obese Diabetic Mice through Activation of SIRT1/PGC-1αin Skeletal Muscle

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Fengxia Liang ◽  
Rui Chen ◽  
Atsushi Nakagawa ◽  
Makoto Nishizawa ◽  
Shinichi Tsuda ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Fasting Blood Glucose ◽  
Low Frequency ◽  
Tolerance Test ◽  
Sirtuin 1 ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Obesity And Diabetes

Electroacupuncture (EA) has been observed to reduce insulin resistance in obesity and diabetes. However, the biochemical mechanism underlying this effect remains unclear. This study investigated the effects of low-frequency EA on metabolic action in genetically obese and type 2 diabetic db/db mice. Nine-week-old db/m and db/db mice were randomly divided into four groups, namely, db/m, db/m + EA, db/db, and db/db + EA. db/m + EA and db/db + EA mice received 3-Hz electroacupuncture five times weekly for eight consecutive weeks. In db/db mice, EA tempered the increase in fasting blood glucose, food intake, and body mass and maintained insulin levels. In EA-treated db/db mice, improved insulin sensitivity was established through intraperitoneal insulin tolerance test. EA was likewise observed to decrease free fatty acid levels in db/db mice; it increased protein expression in skeletal muscle Sirtuin 1 (SIRT1) and induced gene expression of peroxisome proliferator-activated receptor coactivator (PGC-), nuclear respiratory factor 1 (NRF1), and acyl-CoA oxidase (ACOX). These results indicated that EA offers a beneficial effect on insulin resistance in obese and diabetic db/db mice, at least partly, via stimulation of SIRT1/PGC-, thus resulting in improved insulin signal.

scholarly journals AMPK and PPARβ positive feedback loop regulates endurance exercise training-mediated GLUT4 expression in skeletal muscle

2019 ◽  
Vol 316 (5) ◽  
pp. E931-E939 ◽  
Author(s):  
Jin-Ho Koh ◽  
Chad R. Hancock ◽  
Dong-Ho Han ◽  
John O. Holloszy ◽  
K. Sreekumaran Nair ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glut4 Expression ◽  
Amp Activated Protein Kinase ◽  
Response To Exercise ◽  
Glucose Transporter Type 4

The objective of this study is to determine whether AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), or peroxisome proliferator-activated receptor β (PPARβ) can independently mediate the increase of glucose transporter type 4 (GLUT4) expression that occurs in response to exercise training. We found that PPARβ can regulate GLUT4 expression without PGC-1α. We also found AMPK and PPARβ are important for maintaining normal physiological levels of GLUT4 protein in the sedentary condition as well following exercise training. However, AMPK and PPARβ are not essential for the increase in GLUT4 protein expression that occurs in response to exercise training. We discovered that AMPK activation increases PPARβ via myocyte enhancer factor 2A (MEF2A), which acted as a transcription factor for PPARβ. Furthermore, exercise training increases the cooperation of AMPK and PPARβ to regulate glucose uptake. In conclusion, cooperation between AMPK and PPARβ via NRF-1/MEF2A pathway enhances the exercise training mediated adaptive increase in GLUT4 expression and subsequent glucose uptake in skeletal muscle.

scholarly journals Lactate overload inhibits myogenic activity in C2C12 myotubes

2019 ◽  
Vol 14 (1) ◽  
pp. 29-37 ◽  
Author(s):  
Sarah Se-Jung Oh ◽  
Sujin Kim ◽  
Sohee Moon ◽  
Dong-Ho Park ◽  
Ju-Hee Kang
Keyword(s):  
Muscle Atrophy ◽  
Adenosine Monophosphate ◽  
Sirtuin 1 ◽  
In Vivo Studies ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Control Myotubes ◽  
Early Effects

AbstractLactate (LA), an endogenous metabolite produced from pyruvate, can accumulate in skeletal muscle in certain conditions including major diseases, as well as during intensive exercise. Using differentiated C2C12 myotubes, we evaluated the early (1-h) and delayed (24-h) effects of LA (8 mM) on mechanisms involved in myogenesis or muscle atrophy, including 5'-adenosine monophosphate-activated protein kinase (AMPK)-mediated inhibition of protein synthesis through the mTOR/P70-S6K pathway, Akt-mediated inhibition of expression of the MAFbx atrophic factor by FOXO3a and expression of the myogenic transcription factors, MyoD, myogenin and myosin heavy chain. Although the early effects of LA overload were not significant on myogenic or atrophic mechanisms, LA treatment for 24 h significantly activated atrophic mechanisms but suppressed myogenesis in myotubes. In addition, LA overload for 24 h significantly suppressed the expression of Sirtuin 1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha. Consistent with LA-induced activation of atrophic mechanisms, the diameter of C2C12 myotubes treated with LA for 24 h, but not for 1 h, was significantly lower than in control myotubes. Thus, a sustained, but not a transient, LA overload could induce muscle atrophy through the regulation of AMPK- and Akt-mediated pathways, although further in vivo studies are needed to confirm this.

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