Extended Data Fig. 4: Multi-tissue metabolomics comparison.
See also Fig. 1a for experimental setup. Ctrl: healthy controls, no tumour; Non-cax: non-cachectic tumour mice; Pre-cax: pre-cachectic tumour mice; Cax: cachectic tumour mice. n = 4 animals per group. (a-h) Number of metabolites significantly up- or down-regulated in the different tissues of Non-Cax, Pre-Cax and Cax mice compared to Ctrl, organised by class. Metabolites altered in a similar manner between different groups are depicted as follows: Non-Cax/Ctrl vs. Cax/Ctrl (Non x Cax), Pre-cax/Ctrl vs. Cax/Ctrl (Pre x Cax). (i-j) Tables showing the number of metabolites which are altered in a similar manner between the different tissues of Cax mice analysed: up-regulated metabolites (i), down-regulated metabolites (j). Comparison of Cax/Ctrl for cachexia-target tissues and Cax/Non-Cax for tumours. (k-l) Number of metabolites that are commonly up- or down-regulated in at least 2 cachexia target tissues (plasma, liver, adipose tissue, cardiac and skeletal muscles) of Cax mice compared to Ctrl (k) and Non-cax (l), excluding tumour tissues, and organised by class. Statistical analysis (a-l): one way ANOVA following post-hoc correction based on Tukey’s honesty significant difference procedure. See also Supplemental Data Table 1 for log-transformed imputed data, log2 fold change and p values for each tissue. (m-o) Bar graphs showing relative levels of substrates and products of one-carbon metabolism and related pathways in tumour groups vs. Ctrl. From top to bottom: iWAT (m), soleus (n) and tumour (o). Metabolites are similar to the list presented in Fig. 3b. (p) SAH/SAM ratio in cachexia-target tissues and tumour. (q) THF/5-methyl-THF ratio in liver. Data are mean ± s.e.m. Statistical analysis (m-o) based on raw data (MS signal intensities, arbitrary units A.U.). (m-q) One-way ANOVA with Dunnett’s post-hoc tests or Kruskal-Wallis with Dunn’s post-hoc tests vs. Ctrl (cachexia-target tissues) or Non-cax (tumours). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 compared to Ctrl group.
