Fig. 4.

Perturbation of hepatic cholesterol homeostasis in Ehhadh KO mice. A Venn diagram comparing the number of DEG detected by both DESeq2 and limma technologies. All gene names are provided, and those belonging to the cholesterol biosynthesis pathway are highlighted. B Enrichment plot for the HALLMARK CHOLESTEROL HOMEOSTASIS gene set in the molecular signature database (M5892). The graph shows the profile of the running Enrichment Score (ES) and the positions of gene set members on the fold-change rank-ordered list. Overall the NES was 2.338538 with an FDR q-value of 0. C Immunoblots for HMGCR, MVK, PMVK and the loading control citrate synthase (CS) in WT and Ehhadh KO mice (n = 4 per genotype, male mice), and the corresponding quantification. D Cholesterol synthesis was calculated from the incorporation of deuterium isotopes (²H) into cholesterol in the liver. E Hepatic cholesterol content (mg/g tissue) was measured by mass spectrometry. Data are represented individually with the mean ± SD. Statistical significance was tested using unpaired t-test with Welch’s correction (C) or two-way ANOVA with “Genotype” and “Sex” as the two factors followed by Tukey's multiple comparisons test (D, E). *P < 0.05; **P < 0.01; ***P < 0.001