Synergistic effects of resveratrol and exercise on muscle mitochondrial biogenesis require SirT1
Event details
| Date | 03.07.2012 |
| Hour | 10:30 › 11:30 |
| Speaker |
Keir MENZIES Muscle Health Research Center, Toronto, Canada |
| Location | |
| Category | Conferences - Seminars |
Exercise is known to induce dramatic effects on skeletal muscle mitochondrial bioenergetics and substrate utilization. Furthermore, it has been proposed that the histone deacetylase SirT1 plays a pivotal role in these adaptations by way of cellular metabolic sensing in response to energy and metabolite flux. In addition, the metabolic benefits that occur with resveratrol (RSV) treatment for the prevention or amelioration of obesity, diabetes and cardiovascular disease are also proposed to be SirT1-dependent. Hence, to examine the role of SirT1 on exercise- or RSV-induced mitochondrial biogenesis in skeletal muscle, we trained WT and muscle-specific SirT1-deficient (KO) mice on voluntary running wheels, or fed them a 1g/Kg RSV diet for a period of 9 weeks. Here we show that deficits in COX activity, state 3 and state 4 mitochondrial respiration and elevated ROS levels in KO mice were improved with RSV treatment and rescued to WT values with training. Interestingly, the combination of training with RSV feeding resulted in a synergistic increase in COX activity, mitochondrial mass and Nampt expression in WT animals, but not in the KO animals. This SirT1-dependent synergistic increase in mitochondrial content was confirmed in differentiated C2C12 myotubes treated with chronic contractile activity (CCA), a cell culture model of exercise, in combination with RSV. The combined treatment in myotubes elevated both SirT1 and PGC-1α expression and nuclear translocation, along with COX activity, mitochondrial mass and cytochrome c expression. These data uniquely suggest that SirT1 is partially responsible for the maintenance of mitochondria and fatigue resistance in muscle, while also attenuating mitochondrial ROS generation. In addition, SirT1 is important for the synergistic effect of RSV on exercise-induced mitochondrial biogenesis indicating that the therapeutic potential of RSV may rely on a cellular environment that experiences repeated energy demands.
Practical information
- General public
- Free
Organizer
- Kristina Schoonjans et Johan Auwerx
Contact
- Johan Auwerx