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.

The effect of diet-induced obesity on extracellular matrix remodeling during skeletal muscle regeneration

Diet-induced obesity has previously been shown to occur with the concomitant rise in the expression of proin-flammatory cytokines and increases in collagen deposition.While it has been known that the regenerative process of skeletal muscle is altered in obese mice following an acute muscle injury,we sought to examine differences in the expression of various markers of extracellular matrix remodeling and repair.Our laboratory has previously reported an impaired inflammatory and protein synthetic signaling in these mice that may contribute negatively to the muscle regenerative process.To expand upon this previous investigation,tissues from these animals un-derwent further analysis to determine the extent of changes to the regenerative response within the extracellular matrix,including transcriptional changes in CollagenⅠ,CollagenⅢ,and Fibronectin.Here,we show that the expression of CollagenⅢ:Ⅰis significantly increased at 3-days post-injury in obese injured animals compared to lean injured animals(p=0.0338),and by 28-days the obese injured animals exhibit a significantly lower CollagenⅢ:Ⅰthan their lean injured counterparts(p=0.0035).We demonstrate an impaired response to an acute muscle injury in obese mice when compared with lean counterparts.However,further studies are required to elucidate translational consequences of these changes,as well as to determine any causative mechanisms that may be driving this effect.