Effects of PGC-1αoverexpression on the myogenic response during skeletal muscle regeneration

The ability of skeletal muscle to regenerate from injury is crucial for locomotion,metabolic health,and quality of life.Peroxisome proliferator-activated receptor-γcoactivator-1α(PGC1A)is a transcriptional coactivator required for mitochondrial biogenesis.Increased mitochondrial biogenesis is associated with improved muscle cell differentiation,however PGC1A's role in skeletal muscle regeneration following damage requires further investigation.The purpose of this study was to investigate the role of skeletal muscle-specific PGC1A overexpression during regeneration following damage.22 C57BL/6J(WT)and 26 PGC1A muscle transgenic(A1)mice were injected with either phosphate-buffered saline(PBS,uninjured control)or Bupivacaine(MAR,injured)into their tibialis anterior(TA)muscle to induce skeletal muscle damage.TA muscles were extracted 3-or 28-days postinjury and analyzed for markers of regenerative myogenesis and protein turnover.Pgc1a mRNA was~10–20 fold greater in A1 mice.Markers of protein synthesis,AKT and 4EBP1,displayed decreases in A1 mice compared to WT at both timepoints indicating a decreased protein synthetic response.Myod mRNA was~75%lower compared to WT 3 days post-injection.WT mice exhibited decreased cross-sectional area of the TA muscle at 28 days post-injection with bupivacaine compared to all other groups.PGC1A overexpression modifies the myogenic response during regeneration.

Neither autophagy nor exercise training mode affect exercise-induced beneficial adaptations in high fat-fed mice

Exercise mitigates obesity-associated pathologies;however,there is controversy regarding optimal exercise interventions.Autophagy,is known to decrease during obesity and is an important moderator for exercise adaptations.Purpose:To investigate individual and combined effects of different exercise interventions and autophagy inhibition on exercise adaptations during obesity.Methods:C57BL/6J mice initiated 45%high fat diet at 8 weeks of age.After 6 weeks of diet,animals were divided into moderate(MOD)or high intensity interval training interventions(HIIT),animals were further divided into autophagy inhibition or vehicle conditions(n=10/group).Animals exercised and autophagy was inhibited 3X/week by NSC185058 injections,thereby blocking autophagosome formation.Interventions continued for 4 weeks.Results:High fat diet impaired glucose handling~17%;exercise interventions normalized glucoregulation to prehigh fat diet levels,without differences between any interventions.High fat diet induced~25%decrease in aerobic capacity,which returned to baseline after exercise interventions,with no differences between any interventions.No effects of autophagy inhibition were noted.Conclusions:HIIT and MOD training confer similar health-related adaptations.