Extended Data Fig. 6: The liver response to four weeks of high-fat diet.

a, Plasma (mg/dl) and liver (ug/mg protein) cholesterol measurements in male and female APOE cKO and female D374Y mice together with their respective littermate controls 4 weeks after Tamoxifen administration and maintained on a HFD. Plasma: n = 7 APOE cKO and n = 3 littermate control mice; n = 10 D374Y and n = 12 littermate control mice. Liver: n = 8 APOE cKO and n = 7 littermate control mice; n = 5 D374Y and n = 6 littermate control mice. All plots are ± SEM. Statistical analysis was performed with two-sided t-test. b Hematoxylin and eosin staining of paraffin sections of the liver from D374Y and littermate control mice 4 weeks after Tamoxifen administration and maintained on a HFD (scale bar =100 μm, n = 2 vs 2 in each group, where n represents a different mouse). c, Volcano plot of differentially expressed genes after 4 weeks of high-fat diet following tamoxifen-induction in APOE cKO or D374Y mice versus respective littermate controls as determined by mRNA-seq (p value from DESeq2 two-sided Wald test). d, Expression in liver cells of the differentially expressed genes conserved in both strains. e, Expression in 76 human single cell types of the 27 conserved genes from APOE cKO and D374Y alleles 4 weeks after Tamoxifen administration and maintained on a HFD. f, Reactome pathways of genes differentially regulated only in littermate control mice after 4 weeks of HFD. g, expression pattern of HFD-only induced genes in the liver cells.