Sirtuin 1-mediated Effects of Exercise and Resveratrol on Mitochondrial Biogenesis

The purpose of this study was to evaluate the role of sirtuin 1 (SirT1) in exercise- and resveratrol (RSV)-induced skeletal muscle mitochondrial biogenesis. Using muscle-specific SirT1-deficient (KO) mice and a cell culture model of differentiated myotubes, we compared the treatment of resveratrol,...

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Bibliographic Details
Published in:The Journal of biological chemistry 2013-03, Vol.288 (10), p.6968-6979
Main Authors: Menzies, Keir J., Singh, Kaustabh, Saleem, Ayesha, Hood, David A.
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus - drug effects
AMP-Activated Protein Kinases - metabolism
Animals
Cell Line
Cell Nucleus - drug effects
Cell Nucleus - metabolism
Cytochrome c Oxidase Activity
Exercise
Immunoblotting
Metabolism
Mice
Mice, Knockout
Mice, Transgenic
Microscopy, Fluorescence
Mitochondria, Muscle - drug effects
Mitochondria, Muscle - metabolism
Mitochondrial Biogenesis
Mitochondrial Respiration
Muscle Contraction - drug effects
Muscle Fibers, Skeletal - drug effects
Muscle Fibers, Skeletal - metabolism
Muscle Fibers, Skeletal - physiology
Muscle, Skeletal - drug effects
Muscle, Skeletal - metabolism
Muscle, Skeletal - physiology
Nampt
p38 Mitogen-Activated Protein Kinases - metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
PGC-1α
Phosphorylation - drug effects
Physical Conditioning, Animal - physiology
Reactive Oxygen Species (ROS)
Reactive Oxygen Species - metabolism
Resveratrol
Sirt1
Sirtuin 1 - genetics
Sirtuin 1 - metabolism
Skeletal Muscle
Stilbenes - pharmacology
Trans-Activators - metabolism
Transcription Factors
Vasodilator Agents - pharmacology
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Summary:The purpose of this study was to evaluate the role of sirtuin 1 (SirT1) in exercise- and resveratrol (RSV)-induced skeletal muscle mitochondrial biogenesis. Using muscle-specific SirT1-deficient (KO) mice and a cell culture model of differentiated myotubes, we compared the treatment of resveratrol, an activator of SirT1, with that of exercise in inducing mitochondrial biogenesis. These experiments demonstrated that SirT1 plays a modest role in maintaining basal mitochondrial content and a larger role in preserving mitochondrial function. Furthermore, voluntary exercise and RSV treatment induced mitochondrial biogenesis in a SirT1-independent manner. However, when RSV and exercise were combined, a SirT1-dependent synergistic effect was evident, leading to enhanced translocation of PGC-1α and SirT1 to the nucleus and stimulation of mitochondrial biogenesis. Thus, the magnitude of the effect of RSV on muscle mitochondrial biogenesis is reliant on SirT1, as well as the cellular environment, such as that produced by repeated bouts of exercise. Background: SirT1 regulates mitochondrial biogenesis in various tissues. Results: Exercise combined with resveratrol has a SirT1-dependent synergistic effect on mitochondrial biogenesis, despite individual treatments being SirT1-independent. Conclusion: SirT1 is important for maintaining muscle mitochondrial content and function. Significance: The dependence of muscle mitochondrial biogenesis on SirT1 depends on the metabolic state of the muscle.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M112.431155