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SUMMARY:Synergistic effects of resveratrol and exercise on muscle mitochon
 drial biogenesis require SirT1
DTSTART:20120703T103000
DTEND:20120703T113000
DTSTAMP:20260427T200818Z
UID:5c09f3e54a15e36ac377a5d6fb438367004d7465dc24363b638ccbde
CATEGORIES:Conferences - Seminars
DESCRIPTION:Keir MENZIES\nMuscle Health Research Center\, Toronto\, Canada
 \nExercise is known to induce dramatic effects on skeletal muscle mitochon
 drial bioenergetics and substrate utilization. Furthermore\, it has been p
 roposed that the histone deacetylase SirT1 plays a pivotal role in these a
 daptations by way of cellular metabolic sensing in response to energy and 
 metabolite flux. In addition\, the metabolic benefits that occur with resv
 eratrol (RSV) treatment for the prevention or amelioration of obesity\, di
 abetes and cardiovascular disease are also proposed to be SirT1-dependent.
  Hence\, to examine the role of SirT1 on exercise- or RSV-induced mitochon
 drial biogenesis in skeletal muscle\, we trained WT and muscle-specific Si
 rT1-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 acti
 vity\, state 3 and state 4 mitochondrial respiration and elevated ROS leve
 ls in KO mice were improved with RSV treatment and rescued to WT values wi
 th training. Interestingly\, the combination of training with RSV feeding 
 resulted in a synergistic increase in COX activity\, mitochondrial mass an
 d Nampt expression in WT animals\, but not in the KO animals. This SirT1-d
 ependent synergistic increase in mitochondrial content was confirmed in di
 fferentiated C2C12 myotubes treated with chronic contractile activity (CCA
 )\, a cell culture model of exercise\, in combination with RSV. The combin
 ed treatment in myotubes elevated both SirT1 and PGC-1α expression and nu
 clear translocation\, along with COX activity\, mitochondrial mass and cyt
 ochrome 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 deman
 ds.
LOCATION:AI 1153 https://plan.epfl.ch/?room==AI%201153
STATUS:CONFIRMED
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