Extended Data Fig. 10: One-carbon metabolism activation in the humanised SW480 model.
(a-h) Tracing experiment using isotopically labelled glucose ([13C6]-glucose) in healthy controls (Ctrl, grey, n = 4 animals) or cachectic SW480 tumour mice (human colon carcinoma, Cax, dark orange, n = 5 animals). See also Fig. 8c for experimental setup. (a) Initial body weight. (b) Final body, lean and fat mass. (c) Body weight loss expressed as percentage of initial body weight. (d) Final tissue weights (GC muscle, eWAT, iWAT). (e) Final tumour weight. (f) Relative mRNA expression level of key enzymes of one-carbon metabolism and related pathways in eWAT from Ctrl and Cax mice. Data expressed as fold change of Ctrl. (g-i) Metabolite levels of one-carbon metabolism and related pathways in heart (g), soleus (h) and iWAT (i). Metabolites are similar to the list presented in Fig. 3b. Statistical analysis on raw data (2−ΔCt values and MS signal intensities, arbitrary units A.U.). (j-k) Incorporation of labelled carbons from [13C6]-glucose into metabolites of the TCA cycle in soleus muscles (j) and heart (k). Unlabelled metabolites are referred as M + 0, isotopically labelled metabolites as M + X, where X represents the number of labelled carbon atoms. Data are presented as % of total metabolite levels. Data are mean ± s.e.m. Statistical analysis: two-tailed, non-adjusted, Student’s t test or Mann and Whitney’s test (a-i). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.
