Figure 4.

Effect of long-term high-fat diet feeding on liver toxicity, non-alcoholic fatty liver, and circadian rhythm gene expression in the liver of wild-type and G6PD^S188Frats.A, G6PD activity decreased in the liver of G6PD^S188F rats as compared to wild-type (WT) rats fed with normal chow (NC) and high-fat diet (HFD). B and C, PCA plot and sample correlation heat map demonstrating differential metabolism in the liver of WT and G6PD^S188F fed with NC and HFD. D, KEGG enrichment pathway analysis identified the top 25 pathways in response to G6PD mutation. E, IPA Tox Analysis result based on the Liver HFD metabolic dataset shows that liver steatosis is significantly (activation z-score = −1.88) inhibited in response to G6PD mutation. F, G6PD can regulate eight out of 14 compounds that affect hepatic steatosis as an upstream regulator. Prediction legends showing various symbols and arrows for interpretation of the IPA analysis are from Figure 2. Two-way ANOVA with post hoc Tukey’s multiple comparison tests was used to compare multiple groups. ∗∗p < 0.01 and ∗∗∗∗p < 0.001.