Figure 4.

Metabolite profiling in Ehhadh KO male kidneys. (A) Pathway enrichmentanalysis using significantly altered Human Metabolome Database metabolites. Scatterplot represents unadj P values from integrated enrichment analysis and impact values from pathway topology analysis. The node color is on the basis of the P values and the node radius represents the pathway impact values. The only significantly altered KEGG pathway using Fisher’s exact t test (adj P<0.05) was “Sphingolipid metabolism”. (B) Glucosyl- and lactosyl-ceramides levels in WT (n=7) and Ehhadh KO (n=5) male mice. The scaled imputed data (Scaled Imp Data) represent the normalized raw area counts of each metabolite rescaled to set the median equal to 1. Any missing values are imputed with the minimum value. (C) Immunoblots of SPTLC2 and the loading control citrate synthase in WT (n=3 per sex) and Ehhadh KO (n=4 per sex) mice, and the corresponding quantification. Data are presented as mean±SD with individual values plotted (B) and (C). Statistical significance was tested using unpaired t test with Welch’s correction (B) or two-way ANOVA with “Genotype” and “Sex” as the two factors, followed by Tukey's multiple comparisons test (C). *P<0.05; **P<0.01; ***P<0.001.