Peroxisome Proliferator-Activated Receptor (PPAR) γ and Retinoid X Receptor (RXR) agonists have complementary effects on glucose and lipid metabolism in human skeletal muscle

The root ofAtractylodes macrocephalaKoidzumi (Atractylodis Rhizoma Alba, ARA) is a Traditional Korean Medicine and has been commonly used for weight control. Mitochondrial dysfunction appears to be a key contributor to insulin resistance, and therefore mitochondrial targeting drugs represent an important potential strategy for the treatment of insulin resistance and obesity. In this study, the authors investigated the regulatory effects of ARA on mitochondrial function with respect to the stimulation of glucose and lipid metabolism in C2C12 myotubes. After differentiating C2C12 myotubes, cells were treated with or without different concentrations (0.2, 0.5, and 1.0 mg/mL) of ARA extract. ARA extract significantly increased the expression of peroxisome proliferator-activated receptor coactivator 1 alpha (PGC1α) and the downregulations of its targets, nuclear respiratory factor-1 (NRF-1), transcription factor A (TFAM), and total ATP content in C2C12 myotubes. ARA extract also increased the expressions of PGC1αactivator and of the metabolic sensors, AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase and sirtuin (SIRT) 1. Furthermore, it significantly increased glucose uptake by enhancing glucose consumption and subsequently decreased FFA contents and increased carnitine palmitoyltransferase (CPT) 1b expression. Our study indicates that ARA has a potential for stimulating mitochondrial function and energy metabolism in muscle.

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Effect of resistance exercise intensity on the expression of PGC-1α isoforms and the anabolic and catabolic signaling mediators, IGF-1 and myostatin, in human skeletal muscle

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2016-0047 ◽

2016 ◽

Vol 41 (8) ◽

pp. 856-863 ◽

Cited By ~ 14

Author(s):

Neil A. Schwarz ◽

Sarah K. McKinley-Barnard ◽

Mike B. Spillane ◽

Thomas L. Andre ◽

Joshua J. Gann ◽

...

Keyword(s):

Skeletal Muscle ◽

Resistance Exercise ◽

Mrna Expression ◽

Exercise Intensity ◽

Human Skeletal Muscle ◽

Peroxisome Proliferator ◽

Transcriptional Expression ◽

Lower Intensity ◽

Peroxisome Proliferator Activated Receptor ◽

Body Resistance

The purpose of this study was to investigate the acute messenger (mRNA) expression of the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) isoforms, insulin-like growth factor-1Ea (IGF-1Ea), and myostatin in response to 2 resistance exercise intensities. In a uniform-balanced, crossover design, 10 participants performed 2 separate testing sessions involving a lower body resistance exercise component consisting of a lower intensity (50% of 1-repetition maximum; 1RM) protocol and a higher intensity (80% of 1RM) protocol of equal volumes. Muscle samples were obtained at before exercise, 45 min, 3 h, 24 h, and 48 h postexercise. Resistance exercise did not alter total PGC-1α mRNA expression; however, distinct responses of each PGC-1α isoform were observed. The response of each isoform was consistent between sessions, suggesting no effect of resistance exercise intensity on the complex transcriptional expression of the PGC-1α gene. IGF-1Ea mRNA expression significantly increased following the higher intensity session compared with pre-exercise and the lower intensity session. Myostatin mRNA expression was significantly reduced compared with pre-exercise values at all time points with no difference between exercise intensity. Further research is needed to determine the effects of the various isoforms of PGC-1α in human skeletal muscle on the translational level as well as their relation to the expression of IGF-1 and myostatin.

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Impact of the peroxisome proliferator activated receptor-γ coactivator-1β (PGC-1β) Ala203Pro polymorphism on in vivo metabolism, PGC-1β expression and fibre type composition in human skeletal muscle

Diabetologia ◽

10.1007/s00125-007-0729-6 ◽

2007 ◽

Vol 50 (8) ◽

pp. 1615-1620 ◽

Cited By ~ 17

Author(s):

C. Ling ◽

L. Wegner ◽

G. Andersen ◽

P. Almgren ◽

T. Hansen ◽

...

Keyword(s):

Skeletal Muscle ◽

Fibre Type ◽

Human Skeletal Muscle ◽

Peroxisome Proliferator ◽

In Vivo Metabolism ◽

Peroxisome Proliferator Activated Receptor ◽

Fibre Type Composition ◽

Type Composition

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Faculty Opinions recommendation of siRNA-based gene silencing reveals specialized roles of IRS-1/Akt2 and IRS-2/Akt1 in glucose and lipid metabolism in human skeletal muscle.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1046942.496969 ◽

2006 ◽

Author(s):

Stefano Schiaffino

Keyword(s):

Skeletal Muscle ◽

Lipid Metabolism ◽

Gene Silencing ◽

Human Skeletal Muscle ◽

Glucose And Lipid Metabolism

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Fasting and exercise differentially regulate BDNF mRNA expression in human skeletal muscle

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2014-0290 ◽

2015 ◽

Vol 40 (1) ◽

pp. 96-98 ◽

Cited By ~ 14

Author(s):

Jeremy J. Walsh ◽

Brittany A. Edgett ◽

Michael E. Tschakovsky ◽

Brendon J. Gurd

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Neurotrophic Factor ◽

Human Skeletal Muscle ◽

Peroxisome Proliferator ◽

Bdnf Gene ◽

Bdnf Mrna ◽

Peroxisome Proliferator Activated Receptor ◽

Energetic Stress ◽

Future Work

Brain-derived neurotrophic factor (BDNF) gene expression was measured in human skeletal muscle following 3 intensities of exercise and a 48-h fast. No change in BDNF mRNA was observed following exercise, while fasting upregulated BDNF by ∼3.5-fold. These changes were dissociated from changes in peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) following exercise (+2- to 15-fold) and fasting (∼–25%). These results challenge our understanding of the response of BDNF to energetic stress and highlight the importance of future work in this area.

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