AICAR stimulates mitochondrial biogenesis and BCAA catabolic enzyme expression in C2C12 myotubes

Biochimie ◽  
2021 ◽  
Author(s):  
Jason S. Hinkle ◽  
Caroline N. Rivera ◽  
Roger A. Vaughan
Keyword(s):  
Mitochondrial Biogenesis ◽  
C2c12 Myotubes ◽  
Enzyme Expression ◽  
Catabolic Enzyme

scholarly journals Pterostilbene Enhances Endurance Capacity via Promoting Skeletal Muscle Adaptations to Exercise Training in Rats

Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 186 ◽  
Author(s):  
Jiawei Zheng ◽  
Wujian Liu ◽  
Xiaohui Zhu ◽  
Li Ran ◽  
Hedong Lang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Mitochondrial Biogenesis ◽  
C2c12 Myotubes ◽  
Endurance Capacity ◽  
Muscle Adaptations ◽  
Slow Twitch ◽  
Slow Twitch Fibers ◽  
Skeletal Muscle Adaptations

It has been demonstrated that skeletal muscle adaptions, including muscle fibers transition, angiogenesis, and mitochondrial biogenesis are involved in the regular exercise-induced improvement of endurance capacity and metabolic status. Herein, we investigated the effects of pterostilbene (PST) supplementation on skeletal muscle adaptations to exercise training in rats. Six-week-old male Sprague Dawley rats were randomly divided into a sedentary control group (Sed), an exercise training group (Ex), and exercise training combined with 50 mg/kg PST (Ex + PST) treatment group. After 4 weeks of intervention, an exhaustive running test was performed, and muscle fiber type transformation, angiogenesis, and mitochondrial content in the soleus muscle were measured. Additionally, the effects of PST on muscle fiber transformation, paracrine regulation of angiogenesis, and mitochondrial function were tested in vitro using C2C12 myotubes. In vivo study showed that exercise training resulted in significant increases in time-to-exhaustion, the proportion of slow-twitch fibers, muscular angiogenesis, and mitochondrial biogenesis in rats, and these effects induced by exercise training could be augmented by PST supplementation. Moreover, the in vitro study showed that PST treatment remarkably promoted slow-twitch fibers formation, angiogenic factor expression, and mitochondrial function in C2C12 myotubes. Collectively, our results suggest that PST promotes skeletal muscle adaptations to exercise training thereby enhancing the endurance capacity.

scholarly journals Nutrients Stimulate Mitochondrial Biogenesis Via PGC-1α-targeting MiRNAs In C2C12 Myotubes.

2019 ◽  
Vol 51 (Supplement) ◽  
pp. 499-500
Author(s):  
Claudia Pérez López ◽  
Tsubasa Shibaguchi ◽  
Kazumi Masuda
Keyword(s):  
Mitochondrial Biogenesis ◽  
C2c12 Myotubes

scholarly journals Regenerative Response of Degenerate Human Nucleus Pulposus Cells to GDF6 Stimulation

2020 ◽  
Vol 21 (19) ◽  
pp. 7143
Author(s):  
Tom Hodgkinson ◽  
Hamish T. J. Gilbert ◽  
Tej Pandya ◽  
Ashish D. Diwan ◽  
Judith A. Hoyland ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Annulus Fibrosus ◽  
Therapeutic Strategies ◽  
Signalling Pathways ◽  
Signal Transduction Pathways ◽  
Enzyme Expression ◽  
Nucleus Pulposus Cells ◽  
Ivd Degeneration ◽  
Homeostatic Mechanisms ◽  
Catabolic Enzyme

Growth differentiation factor (GDF) family members have been implicated in the development and maintenance of healthy nucleus pulposus (NP) tissue, making them promising therapeutic candidates for treatment of intervertebral disc (IVD) degeneration and associated back pain. GDF6 has been shown to promote discogenic differentiation of mesenchymal stem cells, but its effect on NP cells remains largely unknown. Our aim was to investigate GDF6 signalling in adult human NP cells derived from degenerate tissue and determine the signal transduction pathways critical for GDF6-mediated phenotypic changes and tissue homeostatic mechanisms. This study demonstrates maintained expression of GDF6 receptors in human NP and annulus fibrosus (AF) cells across a range of degeneration grades at gene and protein level. We observed an anabolic response in NP cells treated with recombinant GDF6 (increased expression of matrix and NP-phenotypic markers; increased glycosaminoglycan production; no change in catabolic enzyme expression), and identified the signalling pathways involved in these responses (SMAD1/5/8 and ERK1/2 phosphorylation, validated by blocking studies). These findings suggest that GDF6 promotes a healthy disc tissue phenotype in degenerate NP cells through SMAD-dependent and -independent (ERK1/2) mechanisms, which is important for development of GDF6 therapeutic strategies for treatment of degenerate discs.

Effects of low-dose leucine supplementation on gastrocnemius muscle mitochondrial content and protein turnover in tumor-bearing mice

2019 ◽  
Vol 44 (9) ◽  
pp. 997-1004 ◽  
Author(s):  
Harold W. Lee ◽  
Ella Baker ◽  
Kevin M. Lee ◽  
Aaron M. Persinger ◽  
William Hawkins ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Mitochondrial Biogenesis ◽  
Protein Turnover ◽  
C2c12 Myotubes ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Mitochondrial Content ◽  
Leucine Supplementation ◽  
Tumor Bearing

Many forms of cancer are associated with loss of lean body mass, commonly attributed to decreased protein synthesis and stimulation of proteolytic pathways within the skeletal muscle. Leucine has been shown to improve protein synthesis, insulin signaling, and mitochondrial biogenesis, which are key signaling pathways influenced by tumor signaling. The purpose of this study was to examine the effects of leucine supplementation on mitochondrial biogenesis and protein turnover in tumor-bearing mice. Twenty male C57BL/6 mice were divided into 4 groups (n = 5): Chow, leucine (Leu), Lewis lung carcinoma (LLC) implant, and LLC+Leu. At 9–10 weeks of age, mice were inoculated and supplemented with 5% leucine (w/w) in the diet. C2C12 myotubes were treated with 2.5 mmol/L leucine and 25% LLC conditioned media to further elucidate the direct influence of the tumor and leucine on the muscle. Measures of protein synthesis, mitochondrial biogenesis, and inflammation in the gastrocnemius were assessed via Western blot analysis. Gastrocnemius mass was decreased in LLC+Leu relative to LLC (p = 0.040). Relative protein synthesis rate was decreased in LLC mice (p = 0.001). No change in protein synthesis was observed in myotubes. Phosphorylation of STAT3 was decreased in the Leu group relative to the control in both mice (p = 0.019) and myotubes (p = 0.02), but did not significantly attenuate the inflammatory effect of LLC implantation (p = 0.619). LLC decreased markers of mitochondrial content; however, PGC-1α was increased in LLC+Leu relative to LLC (p = 0.001). While leucine supplementation was unable to preserve protein synthesis or mitochondrial content associated with LLC implantation, it was able to increase mitochondrial biogenesis signaling. Novelty This study provides novel insights on the effect of leucine supplementation on mitochondrial biogenesis and protein turnover in tumor-bearing mice. Leucine increased signaling for mitochondrial biogenesis in the skeletal muscle. Leucine supplementation decreased inflammatory signaling in skeletal muscle.

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 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.

scholarly journals Leucine Modulates Mitochondrial Biogenesis and SIRT1-AMPK Signaling in C2C12 Myotubes

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Chunzi Liang ◽  
Benjamin J. Curry ◽  
Patricia L. Brown ◽  
Michael B. Zemel
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Mitochondrial Biogenesis ◽  
C2c12 Myotubes ◽  
Acid Oxidation ◽  
Ampk Signaling ◽  
Compound C ◽  
Genes Expression ◽  
Sirt1 Inhibitor ◽  
Methyl Butyrate

Previous studies from this laboratory demonstrate that dietary leucine protects against high fat diet-induced mitochondrial impairments and stimulates mitochondrial biogenesis and energy partitioning from adipocytes to muscle cells through SIRT1-mediated mechanisms. Moreover,β-hydroxy-β-methyl butyrate (HMB), a metabolite of leucine, has been reported to activate AMPK synergistically with resveratrol in C2C12 myotubes. Therefore, we hypothesize that leucine-induced activation of SIRT1 and AMPK is the central event that links the upregulated mitochondrial biogenesis and fatty acid oxidation in skeletal muscle. Thus, C2C12 myotubes were treated with leucine (0.5 mM), alanine (0.5 mM), valine (0.5 mM), EX527 (SIRT1 inhibitor, 25 μM), and Compound C (AMPK inhibitor, 25 μM) alone or in combination to determine the roles of AMPK and SIRT1 in leucine-modulation of energy metabolism. Leucine significantly increased mitochondrial content, mitochondrial biogenesis-related genes expression, fatty acid oxidation, SIRT1 activity and gene expression, and AMPK phosphorylation in C2C12 myotubes compared to the controls, while EX527 and Compound C markedly attenuated these effects. Furthermore, leucine treatment for 24 hours resulted in time-dependent increases in cellular NAD+, SIRT1 activity, and p-AMPK level, with SIRT1 activation preceding that of AMPK, indicating that leucine activation of SIRT1, rather than AMPK, is the primary event.

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