Fig. 5: Lithium (Li) treatment improves muscle function and insulin sensitivity in D2 mdx mice subjected to voluntary wheel running (VWR).

a–d Twitch and tetanic specific force production in isolated soleus and EDL muscles is improved in the mdx-VWRLi group (soleus, WT n = 8, mdx-sedentary [SED] n = 9, mdx-VWR n = 10, mdx-VWRLi n = 11; EDL WT n = 8, mdx-SED n = 8, mdx-VWR n = 9, mdx-VWRLi n = 8). e, f Soleus fatigue resistance is enhanced in the mdx-VWR and mdx-VWRLi groups, while in the EDL, fatigue resistance is worse in the mdx-VWR group and restored with lithium supplementation (soleus, mdx-SED n = 9, mdx-VWR n = 10, mdx-VWRLi n = 10; EDL mdx-SED n = 9, mdx-VWR n = 10, mdx-VWRLi n = 10). g, h Muscle histological analysis with H&E staining shows a significant reduction in % necrosis in soleus and EDL muscles obtained from 12-week old mdx-VWRLi mice vs. mdx-SED mice. A significant main effect of muscle type also indicates that EDL muscles have greater % necrosis vs. soleus muscles (soleus, mdx-SED n = 6, mdx-VWR n = 6, mdx-VWRLi n = 5; EDL mdx-SED n = 5, mdx-VWR n = 5, mdx-VWRLi n = 6). i Utrophin expression is higher in in quadricep muscles from mdx-VWR and mdx-VWRLi groups when compared with mdx-SED mice (mdx-SED n = 9, mdx-VWR n = 11, mdx-VWRLi n = 11). j Respiratory exchange ratio (RER) is lowest in the mdx-VWRLi mice when compared to all other mdx groups (n = 10 per group). k–n Insulin tolerance tests and corresponding area-under-the-curve (AUC) analysis, baseline glucose levels and % decline in blood glucose in 12-week old WT, mdx-SED, mdx-VWR, and mdx-VWRLi mice (n = 11 per group; mdx-SED vs. WT = *, mdx-SED vs. mdx-VWR = †; mdx-VWR vs. WT = $; mdx-SED vs. mdx-VWRLi = #). Glucose traces are displayed relative to baseline glucose levels. AUC were obtained from the normalized traces. There were no differences in baseline glucose levels. o, p Average daily and total distance traveled with a cagewheel was lower in mdx-VWRLi mice vs. mdx-VWR mice (n = 11 per group). For (a–d, i, l and n), a Welch’s one-way ANOVA with a Dunnett’s T3 post-hoc test was used. For (e, f), a two-way ANOVA was used to assess main effects of force and time. For (h, j), a two-way ANOVA with a Tukey’s post-hoc test was used; and significant main effects and interactions denoted in the text above. For (k), a two-way repeated ANOVA was used with a Tukey’s post-hoc test. For (m), a one-way ANOVA was used. Significant main effects are denoted in the text above. For (o, p), a a two-tailed Student’s t test was used. All values are mean ± SEM. *p < 0.05, **p < 0.01, and ***p < 0.001. † p< 0.05, †† p < 0.01. # p < 0.05, ## p < 0.01, ### p < 0.0001. $ p < 0.05.