Fig. 7

Ketogenic diets increase the levels of hydroxylated sphingomyelins and acylcarnitines in melanoma xenografts. A Identification of significant differential lipids and lipid-like metabolites in tumors obtained from melanoma-bearing mice treated with CTRL, LCT, or LCT-MCT diet between both KDs and CTRL for each xenograft model by one-way ANOVA and Fisher´s LSD post hoc test. Tumor lipids and lipid-like metabolites were filtered based on an FDR-adjusted p value < 0.05 for both KDs vs. CTRL. The Venn diagram represents the intersections among the 4 xenograft models (A375, WM47, WM3311, WM3000) for significantly upregulated lipids and lipid-like metabolites in tumors (see also Table S16). B–I Principal component analysis (PCA) of B–E sphingomyelins and F-I acylcarnitines quantified in tumor samples of B/F A375, C/G WM47, D/H WM3311, and E/I WM3000 xenograft-bearing mice treated with CTRL, LCT, or LCT-MCT. n = 7–13. J–Q Effect of KDs on sphingomyelin and acylcarnitine pools in tumor tissues. Sum concentration of total J sphingomyelins and N acylcarnitines, K hydroxylated sphingomyelins and O hydroxylated acylcarnitines, L non-hydroxylated sphingomyelins and P non-hydroxylated acylcarnitines, and ratio of hydroxylated to non-hydroxylated fraction of M sphingomyelins and Q acylcarnitines quantified in melanoma xenografts treated with CTRL, LCT, or LCT-MCT. Individual data points ± SD; n = 7–13; p values were determined by a one-way ANOVA with Dunnett’s multiple comparisons test comparing CTRL with each KD group for every xenograft model, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. AC: acylcarnitine, -Non-OH: non-hydroxylated, -OH: hydroxylated, SM: sphingomyelin, ↑: increased