Extended Data Fig. 8: Glucose utilisation in cachectic skeletal and cardiac muscle.
(a-h) Tracing experiment using isotopically labelled glucose ([13C6]-glucose) in healthy controls (Ctrl), non-cachectic (Non-cax), pre-cachectic (Pre-cax) and cachectic (Cax) mice with tumours. n = 4 animals per group. See also Fig. 1a for experimental setup and Fig. 6. (a, b, c) Incorporation of labelled carbons from [13C6]-glucose into metabolites of the TCA cycle in GC muscles (a), soleus (b) and hearts (c). Unlabelled metabolites are referred as M + 0, isotopically labelled metabolites as M + X, where X represent the number of labelled carbon atoms. Data are presented as MS signal intensity (arbitrary units A.U.). (d, e, f) Percentage of labelled metabolites (sum of M + X) out of total metabolites (sum of M + 0 and M + X) detected in GC muscles (d), soleus (e) and hearts (f). Data are mean ± s.e.m. Statistical analysis: unpaired two-way ANOVA with Dunnett’s post-hoc tests vs. Cax. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 compared to Cax (a, b, c), Ctrl or Non-cax (d, e, f). (g-h) Modelling of the fluxes of glucose feeding the TCA cycle in GC muscles Ctrl (grey lines) and Cax mice (statistically significant red lines). For clarity, flux values are plotted separately. Significantly different fluxes are highlighted in red. (h) Flux relative to citrate synthase are presented as interval plots (means and 95% confidence intervals) for Ctrl (grey), Pre-cax (light red) and Cax (dark red) mice. For mathematical modelling and numerical values: please refer to Methods and Supplemental Data Table 2.
