Protein expression following 6 weeks of PGC-1α over-expression.

<p>Slow genes are shown in black (utrophin – A, slow myosin heavy chain – B) oxidative genes are shown in gray (cytochrome C – C, uncoupling protein-1 – D, complex IV subunit IV – E, myoglobin – F, Hsp 60 – G), pathway genes are shown in white (Sirt-1 – H, nuclear respiratory factor -1 – I, p38 – J, phospho-p38 – K), and controls have diagonal lines (Actin – L, Troponin – M, Spectrin – N). Relative change compared to control limbs (n = 6/group) (O). * indicates p<0.05 compared to control limbs.</p

Muscle and body mass following eight weeks of 100 mg/kg resveratrol feeding.

<p>*indicates significantly different from control. N = 8/group. EDL - extensor digitorum longus, Rel – relative, TA – tibialis anterior, Gastroc – gastrocnemius.</p

PGC-1α induced changes in muscle function.

<p>Following four (n = 7) or six (sol n = 6; EDL n = 13) weeks of PGC-1α over-expression muscle function in the soleus and EDL was altered.</p><p>*indicates significantly different from corresponding control. Wk – week, sol – soleus, EDL – extensor digitorum longus, CSA – cross sectional area.</p

PGC-1α over-expression reduces disease-related muscle injury.

<p>10× micrographs of six week old soleus muscles following H and E staining (A and B). (C) The total areas of necrotic, H&E negative, or regenerating cells were quantified and is expressed as a percent of the total soleus area. In addition, laminin was detected with a fluorescently labeled antibody (not shown) in order to determine central nucleation. (D) PGC-1α caused a reduction in central nucleation. N = 5/group; * indicates p<0.05.</p

Resveratrol supplementation increased fatigue resistance in dystrophic skeletal muscle.

<p>One month old mdx mice were fed a diet containing 100 mg/kg/day resveratrol or control diet for eight weeks. Resveratrol feeding increased fatigue resistance in the soleus (A) and force generated during the final contraction (B ) was higher in treated animals when compared to control. n = 8 Con; n = 6 Res; * indicates p<0.05.</p

Virally-mediated gene transfer.

<p>Six weeks following PGC-1α gene delivery total (PGC-1α) and viral (V-PGC-1α) expression was increased in treated limbs compared to untreated limbs (n = 6/group). * indicates p<0.05.</p

PGC-1α protects against muscle fatigue.

<p>Muscle fatigue curves in the soleus (n = 6/group) and EDL (n = 7/group) (A) during 10 minutes of a fatigue protocol where muscles are contracted every second for 10 minutes. Force of the final contraction (B) was significantly higher in the soleus and EDL muscles over-expressing PGC-1α when compared to control muscle. * indicates p<0.05.</p

PGC-1α induced changes in muscle mass.

<p>Following four (n = 7) or six (n = 13) weeks of PGC-1α over-expression in mdx mice muscle mass was generally reduced.</p><p>*indicates significantly different from corresponding control. EDL – extensor digitorum longus, Gastroc – gastrocnemius, TA – tibialis anterior.</p

Resveratrol supplementation did not improve resistance to contraction induced injury.

<p>Feeding a diet containing 100 mg/kg/day resveratrol for eight weeks did not improve resistance to contraction induced injury in (A) the EDL (n = 8 Con; n = 6 Res) or (B) the soleus (n = 8/group) when compared to control.</p

PGC-1α partially maintains diaphragmatic function six months following gene transfer.

<p>Neonatal mdx mice were injected in the sub-xyphiod region in order to cause diaphragmatic infection and sacrificed 6 mo later. Diaphragms over-expressing PGC-1α were more resistant to contraction induced injury (n = 4 Con; n = 7 PGC-1α) (A; Contraction 4 – p = 0.08), however, fatigue resistance was similar between groups (n = 7/group) (B). * indicates p<0.05.</p