Fig. 5

Plasma metabolic alterations induced by ketogenic diets are reflected in the tumor metabolome. A–D Principal component analysis (PCA) of polar metabolite profiling data obtained from A A375, B WM47, C WM331, and D WM3000 melanoma xenografts treated with CTRL, LCT, or LCT-MCT diet. n = 7–13. E, F Identification of significant differential metabolites in tumors between both KDs and CTRL for each xenograft model by one-way ANOVA and Fisher’s LSD post hoc test. Tumor metabolites were filtered based on an FDR-adjusted p value < 0.05 for both KDs vs. CTRL. The Venn diagrams represent the intersections among the 4 xenograft models (A375, WM47, WM3311, WM3000) for significantly E upregulated and F downregulated tumor metabolites (see also Table S9). G–J Overview of metabolic pathway analysis (MetPA) using tumor metabolites of G A375, H WM47, I WM3311, and J WM3000 melanoma-bearing mice. Pathways consistently altered by KDs throughout the melanoma models are highlighted in the MetPA results overview, indicating matched pathways arranged by p values from pathway enrichment analysis (Y-axis) and pathway impact values from pathway topology analysis (X-axis). Node color and radius are based on the p value and pathway impact value, respectively. n = 9–13 in CTRL groups and n = 14–24 in KD groups. Alpha-AAA: alpha-aminoadipic acid, BABA: beta-aminobutyric acid, Cit: Citrulline, HArg, homoarginine, ↑: increased, ↓: decreased