Fig. 6

Ketogenic diets alter sphingomyelin levels in plasma of melanoma xenograft-bearing mice. A Heatmap representing all lipids and lipid-like metabolites quantified in plasma of xenograft-bearing mice treated with CTRL, LCT, or LCT-MCT diet. Lipids and lipid-like metabolites were grouped by compound class. n = 7–13. B Identification of significant differential lipids and lipid-like metabolites in plasma between both KDs and CTRL for each xenograft model by one-way ANOVA and Fisher´s LSD post hoc test. Plasma 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 plasma (see also Table S13). Ninety-five lipids and lipid-like metabolites were consistently upregulated by KDs in melanoma xenografts. The box below the Venn diagram indicates how many lipids and lipid-like metabolites per compound class were included in those 95. The percentage indicates the amount of respective lipids and lipid-like metabolites relative to the total number of quantified lipids and lipid-like metabolites per compound class. C–F Principal component analysis (PCA) of sphingomyelins quantified in plasma samples of C A375, D WM47, E WM3311, and F WM3000 xenograft-bearing mice treated with CTRL, LCT, or LCT-MCT. n = 7–13. G–J Effect of KDs on the total sphingomyelin pool in plasma and on metabolic indicators for sphingomyelin synthesis. Sum concentration of G total sphingomyelins (hydroxylated and non-hydroxylated sphingomyelins), H ratio of sphingomyelins to ceramides, I ratio of sphingomyelins to phosphatidylcholines, and J ratio of glycosyl-ceramides to ceramides quantified in plasma melanoma-bearing mice 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, CE: cholesteryl ester, Cer: ceramide, DG: diglyceride, DH-Cer: dihydroceramide, FA: fatty acid, Glycosyl-Cer: glycosylceramide, LPC: lyso-phosphatidylcholine, PC: phosphatidylcholine, SM: sphingomyelin, TG: triglyceride, ↑: increased