Fig. 1

The metabolome of dystrophin-deficient muscle acutely responds to eccentric challenge. a Principal component analysis of the global metabolic profiles of MDX gastrocnemius muscles before and after eccentric contractions. Unchallenged WT muscles were included as a negative control. Arrows indicate the early chronological progression of injured groups and ellipses indicate 95% confidence intervals. b Heat map of metabolites with significantly different ion abundances in MDX muscle compared to WT (left) and sequential post-injury time points in MDX mice compared to uninjured controls (right). c Volcano plot of biochemical pathways significantly altered in MDX muscle at baseline. Significantly altered metabolites were used to calculate pathway impact and highly affected pathways are indicated. d Fold change of pathway impact scores during the acute (2 h) injury stage of MDX muscle compared to MDX baseline. e Volcano plot of metabolites significantly altered in MDX muscle at baseline. Example components of the NAD metabolome (red), glycolytic intermediates (blue), and polyamine pathway intermediates (green) are indicated. Dashed line indicates the significance threshold of non-adjusted p < 0.05. f Time course box and whisker plots of selected components of the NAD metabolome, glycolytic intermediates (g), and polyamine pathway (h) over 14 days post-challenge. N = 6 mice per time genotype and time point. Whiskers represent minimum and maximum values. Significance was determined by one-way ANOVA with Tukey’s post hoc test (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; ns, not significant; all p values non-adjusted) versus unchallenged WT (red) or MDX (blue) samples