Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases / metabolism
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Active Transport, Cell Nucleus / drug effects
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Animals
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Cell Line
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Immunoblotting
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Mice
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Mice, Knockout
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Mice, Transgenic
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Microscopy, Fluorescence
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Mitochondria, Muscle / drug effects*
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Mitochondria, Muscle / metabolism
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Muscle Contraction / drug effects
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Muscle Fibers, Skeletal / drug effects
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Muscle Fibers, Skeletal / metabolism
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Muscle Fibers, Skeletal / physiology
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Muscle, Skeletal / drug effects
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Muscle, Skeletal / metabolism
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Muscle, Skeletal / physiology
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Phosphorylation / drug effects
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Physical Conditioning, Animal / physiology*
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Reactive Oxygen Species / metabolism
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Resveratrol
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Sirtuin 1 / genetics
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Sirtuin 1 / metabolism*
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Stilbenes / pharmacology*
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Trans-Activators / metabolism
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Transcription Factors
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Vasodilator Agents / pharmacology
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Ppargc1a protein, mouse
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Reactive Oxygen Species
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Stilbenes
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Trans-Activators
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Transcription Factors
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Vasodilator Agents
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p38 Mitogen-Activated Protein Kinases
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AMP-Activated Protein Kinases
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Sirtuin 1
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Resveratrol