scholarly journals Citrus hassaku Extract Powder Increases Mitochondrial Content and Oxidative Muscle Fibers by Upregulation of PGC-1α in Skeletal Muscle

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 497
Author(s):  
Shiori Akashi ◽  
Akihito Morita ◽  
Yusuke Mochizuki ◽  
Fuka Shibuya ◽  
Yasutomi Kamei ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Control Diet ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Mitochondrial Content ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cultured Myotubes ◽  
Citrus Hassaku ◽  
Amp Activated Protein Kinase

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is expressed in skeletal muscles and regulates systemic metabolism. Thus, nutraceuticals targeting skeletal muscle PGC-1α have attracted attention to modulate systemic metabolism. As auraptene contained in citrus fruits promotes lipid metabolism and improves mitochondrial respiration, it could increase mitochondrial function through PGC-1α. Therefore, we hypothesized that PGC-1α is activated by auraptene and investigated its effect using Citrus hassaku extract powder (CHEP) containing >80% of auraptene. C2C12 myotubes were incubated with vehicle or CHEP for 24 h; C57BL/6J mice were fed a control diet or a 0.25% (w/w) CHEP-containing diet for 5 weeks. PGC-1α protein level and mitochondrial content increased following CHEP treatment in cultured myotubes and skeletal muscles. In addition, the number of oxidative fibers increased in CHEP-fed mice. These findings suggest that CHEP-mediated PGC-1α upregulation induced mitochondrial biogenesis and fiber transformation to oxidative fibers. Furthermore, as CHEP increased the expression of the protein sirtuin 3 and of phosphorylated AMP-activated protein kinase (AMPK) and the transcriptional activity of PGC-1α, these molecules might be involved in CHEP-induced effects in skeletal muscles. Collectively, our findings indicate that CHEP mediates PGC-1α expression in skeletal muscles and may serve as a dietary supplement to prevent metabolic disorders.

scholarly journals N-acetyl-L-cysteine Prevents Lactate-Mediated PGC1-alpha Expression in C2C12 Myotubes

Biology ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 44 ◽  
Author(s):  
Minas Nalbandian ◽  
Zsolt Radak ◽  
Masaki Takeda
Keyword(s):  
Lactate Production ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Oxygen Species ◽  
Lactate Metabolism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Intermittent Exposure ◽  
Physiological Adaptations ◽  
Cultured Myotubes

Background: Exercise induces many physiological adaptations. Recently, it has been proposed that some of these adaptations are induced by exercise-mediated lactate production. In this study, we aimed to investigate in vitro the effect of lactate in cultured myotubes and whether antioxidants could inhibit the effect. Methods: Differentiated myotubes were cultured at different concentrations of L-lactate (0, 10, 30, 50 mM) in the absence or presence of an antioxidant, N-acetyl-L-cysteine (Nac). The temporal effect of lactate exposure in myotubes was also explored. Results: Two hours of exposure to 50 mM L-lactate and six hours of exposure to 30 or 50 mM L-lactate caused a significant increase in PGC1-alpha (peroxisome proliferator-activated receptor γ coactivator-1α) expression in the myotubes. This up-regulation was suppressed by 2 mM Nac. Intermittent and continuous lactate exposure caused similar PGC1-alpha up-regulation. These results suggest that the increase in PGC1-alpha expression is mediated by reactive oxygen species (ROS) production from lactate metabolism and that both continuous and intermittent exposure to L-lactate can cause the up-regulation.

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 Electrical stimulation prevents doxorubicin-induced atrophy and mitochondrial loss in cultured myotubes

2019 ◽  
Vol 317 (6) ◽  
pp. C1213-C1228 ◽  
Author(s):  
Blas A. Guigni ◽  
Dennis K. Fix ◽  
Joseph J. Bivona ◽  
Bradley M. Palmer ◽  
James A. Carson ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Ring Finger ◽  
Mechanical Stretch ◽  
Skeletal Muscle Atrophy ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Ros Production ◽  
Mitochondrial Content ◽  
Peroxisome Proliferator Activated Receptor

Muscle contraction may protect against the effects of chemotherapy to cause skeletal muscle atrophy, but the mechanisms underlying these benefits are unclear. To address this question, we utilized in vitro modeling of contraction and mechanotransduction in C2C12 myotubes treated with doxorubicin (DOX; 0.2 μM for 3 days). Myotubes expressed contractile proteins and organized these into functional myofilaments, as electrical field stimulation (STIM) induced intracellular calcium (Ca2+) transients and contractions, both of which were prevented by inhibition of membrane depolarization. DOX treatment reduced myotube myosin content, protein synthesis, and Akt (S308) and forkhead box O3a (FoxO3a; S253) phosphorylation and increased muscle RING finger 1 (MuRF1) expression. STIM (1 h/day) prevented DOX-induced reductions in myotube myosin content and Akt and FoxO3a phosphorylation, as well as increases in MuRF1 expression, but did not prevent DOX-induced reductions in protein synthesis. Inhibition of myosin-actin interaction during STIM prevented contraction and the antiatrophic effects of STIM without affecting Ca2+ cycling, suggesting that the beneficial effect of STIM derives from mechanotransductive pathways. Further supporting this conclusion, mechanical stretch of myotubes recapitulated the effects of STIM to prevent DOX suppression of FoxO3a phosphorylation and upregulation of MuRF1. DOX also increased reactive oxygen species (ROS) production, which led to a decrease in mitochondrial content. Although STIM did not alter DOX-induced ROS production, peroxisome proliferator-activated receptor-γ coactivator-1α and antioxidant enzyme expression were upregulated, and mitochondrial loss was prevented. Our results suggest that the activation of mechanotransductive pathways that downregulate proteolysis and preserve mitochondrial content protects against the atrophic effects of chemotherapeutics.

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 Effects of Caffeine on Metabolism and Mitochondria Biogenesis in Rhabdomyosarcoma Cells Compared with 2,4-Dinitrophenol

2012 ◽  
Vol 5 ◽  
pp. NMI.S10233 ◽  
Author(s):  
Roger A. Vaughan ◽  
Randi Garcia-Smith ◽  
Marco Bisoffi ◽  
Kristina A. Trujillo ◽  
Carole A. Conn
Keyword(s):  
Skeletal Muscle ◽  
Consumption Rate ◽  
Control Treatment ◽  
Peroxisome Proliferator ◽  
Chain Reaction ◽  
Extracellular Acidification ◽  
Mitochondrial Content ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Biosynthesis ◽  
Polymerase Chain

Purpose This work investigated if treatment with caffeine or 2,4-dinitrophenol (DNP) induce expression of peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α) and increase both mitochondrial biosynthesis and metabolism in skeletal muscle. Methods Human rhabdomyosarcoma cells were treated with either ethanol control (0.1% final concentration) caffeine, or DNP at 250 or 500 μM for 16 or 24 hours. PGC-1α RNA levels were determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). PGC-1α protein and mitochondrial content was determined using flow cytometry and immunohistochemistry. Metabolism was determined by quantification of extracellular acidification rate and oxygen consumption rate. Results Treatment with either caffeine or DNP induced PGC-1α RNA and protein as well as mitochondrial content compared with control. Treatment with caffeine and DNP also significantly increased oxidative metabolism and total metabolic rate compared with control. Caffeine similarly increased metabolism and mitochondrial content compared with DNP. Conclusion This work identified that both caffeine and DNP significantly induce PGC-1α, and increase both metabolism and mitochondrial content in skeletal muscle.

scholarly journals Effects of short-term endurance exercise training on acute doxorubicin-induced FoxO transcription in cardiac and skeletal muscle

2014 ◽  
Vol 117 (3) ◽  
pp. 223-230 ◽  
Author(s):  
Andreas N. Kavazis ◽  
Ashley J. Smuder ◽  
Scott K. Powers
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Endurance Exercise ◽  
Skeletal Muscles ◽  
Target Genes ◽  
Ring Finger ◽  
Peroxisome Proliferator ◽  
Short Term ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Impact

Doxorubicin (DOX) is a potent antitumor agent used in cancer treatment. Unfortunately, DOX can induce myopathy in both cardiac and skeletal muscle, which limits its clinical use. Importantly, exercise training has been shown to protect against DOX-mediated cardiac and skeletal muscle myopathy. However, the mechanisms responsible for this exercise-induced muscle protection remain elusive. These experiments tested the hypothesis that short-term exercise training protects against acute DOX-induced muscle toxicity, in part, due to decreased forkhead-box O (FoxO) transcription of atrophy genes. Rats ( n = 6 per group) were assigned to sedentary or endurance exercise-trained groups and paired with either placebo or DOX treatment. Gene expression and protein abundance were measured in both cardiac and skeletal muscles to determine the impact of DOX and exercise on FoxO gene targets. Our data demonstrate that DOX administration amplified FoxO1 and FoxO3 mRNA expression and increased transcription of FoxO target genes [i.e., atrogin-1/muscle atrophy F-box (MaFbx), muscle ring finger-1 (MuRF-1), and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)] in heart and soleus muscles. Importantly, exercise training protected against DOX-induced increases of FoxO1 and MuRF-1 in cardiac muscle and also prevented the rise of FoxO3, MuRF-1, and BNIP3 in soleus muscle. Furthermore, our results indicate that exercise increased peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) in both the heart and soleus muscles. This is important because increased PGC-1α expression is known to suppress FoxO activity resulting in reduced expression of FoxO target genes. Together, these results are consistent with the hypothesis that exercise training protects against DOX-induced myopathy in both heart (FoxO1 and MuRF-1) and skeletal muscles (FoxO3, MuRF-1, and BNIP3).

scholarly journals Up-regulation of pyruvate dehydrogenase kinase isoform 4 (PDK4) protein expression in oxidative skeletal muscle does not require the obligatory participation of peroxisome-proliferator-activated receptor α (PPARα)

2002 ◽  
Vol 366 (3) ◽  
pp. 839-846 ◽  
Author(s):  
Mark J. HOLNESS ◽  
Karen BULMER ◽  
Geoffrey F. GIBBONS ◽  
Mary C. SUGDEN
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Pyruvate Dehydrogenase ◽  
Skeletal Muscles ◽  
Pyruvate Dehydrogenase Kinase ◽  
Glucose Disposal ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Anterior Tibialis

In insulin deficiency, increased lipid delivery and oxidation suppress skeletal-muscle glucose oxidation by inhibiting pyruvate dehydrogenase complex (PDC) activity via enhanced protein expression of pyruvate dehydrogenase kinase (PDK) isoform 4, which phosphorylates (and inactivates) PDC. Signalling via peroxisome-proliferator-activated receptor α (PPARα) is an important component of the mechanism enhancing hepatic and renal PDK4 protein expression. Activation of PPARα in gastrocnemius, a predominantly fast glycolytic (FG) muscle, also increases PDK4 expression, an effect that, if extended to all muscles, would be predicted to drastically restrict whole-body glucose disposal. Paradoxically, chronic activation of PPARα by WY14,643 treatment improves glucose utilization by muscles of insulin-resistant high-fat-fed rats. In the resting state, oxidative skeletal muscles are quantitatively more important for glucose disposal than FG muscles. We evaluated the participation of PPARα in regulating PDK4 protein expression in slow oxidative (SO) skeletal muscle (soleus) and fast oxidative-glycolytic (FOG) skeletal muscle (anterior tibialis) containing a high proportion of oxidative fibres. In the fed state, acute (24h) activation of PPARα by WY14,643 in vivo failed to modify PDK4 protein expression in soleus, but modestly enhanced PDK4 protein expression in anterior tibialis. Starvation enhanced PDK4 protein expression in both muscles, with the greater response in anterior tibialis. WY14,643 treatment in vivo during starvation did not further enhance upregulation of PDK4 protein expression in either muscle type. Enhanced PDK4 protein expression after starvation was retained in SO and FOG skeletal muscles of PPARα-deficient mice. Our data indicate that PDK4 protein expression in oxidative skeletal muscle is regulated by a lipid-dependent mechanism that is not obligatorily dependent on signalling via PPARα.

Effects of acute bouts of running and swimming exercise on PGC-1α protein expression in rat epitrochlearis and soleus muscle

2004 ◽  
Vol 286 (2) ◽  
pp. E208-E216 ◽  
Author(s):  
Shin Terada ◽  
Izumi Tabata
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Skeletal Muscles ◽  
Peroxisome Proliferator ◽  
Ampk Activation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Number Of Factors ◽  
Exercise Induced ◽  
Low Intensity Exercise

The purpose of this study was to elucidate the mechanisms underlying low-intensity exercise-induced peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein expression in rat skeletal muscles. Rats (5–6 wk old) swam without a load and ran on the treadmill at a speed of 13 m/min, respectively, in two 3-h sessions separated by 45 min of rest. PGC-1α content in epitrochlearis muscle (EPI) was increased by 75 and 95%, immediately and 6 h after swimming, respectively, with no increase in PGC-1α content in the soleus (SOL). After running, PGC-1α content in EPI was unchanged, whereas a 107% increase in PGC-1α content was observed in SOL 6 h after running. Furthermore, in EPI and SOL as well as other muscles (triceps, plantaris, red and white gastrocnemius), PGC-1α expression was enhanced concomitant with reduced glycogen postexercise, suggesting that expression of PGC-1α occurs in skeletal muscle recruited during exercise. PGC-1α content in EPI was increased after 18-h in vitro incubation with 0.5 mM 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and 4 mM caffeine. However, AICAR incubation did not affect PGC-1α content in the SOL, whereas caffeine incubation increased it. These results suggest that exercise-induced PGC-1α expression in skeletal muscle may be mediated by at least two exercise-induced signaling factors: AMPK activation and Ca2+ elevation. The number of factors involved (both AMPK and Ca2+, or Ca2+ only) in exercise-induced PGC-1α expression may differ among muscles.

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