Figure 8. Coupling of Acox1^Lampe1 mutation with obesogenic diet stress accelerates hepatic injury and expression of genes associated with HCC development.

Eight-week-old Acox1^Lampe1 mice and WT littermate controls were fed a HFHCD or chow diet for 4 weeks (young) and compared with Acox1^Lampe1 were fed chow diet for 59 weeks (old). (A–E) Hepatic mRNA expression of genes associated with HCC development; H19, Afp, Igfbp1, Fabp5, and Spp1. (F) Upper panel: Representative liver histology (H&E staining; 20×) of the temporal evolution (8, 12, 16, 23, and 59 weeks of age) and histopathological changes in chow-fed Acox1^Lampe1 mice. Acox1^Lampe1 mice display steatosis, increasing inflammation, and liver cell injury over time with development of hepatocellular tumors at 59 weeks of age. Lower panel: Representative liver histology (H&E staining; 20×) of 12-week-old (young) Acox1^Lampe1 and WT mice fed a HFHCD. Acox1^Lampe1 mice display steatosis, inflammation, and liver cell injury after 4 weeks of HFHCD feeding. PT depicts portal tract; arrowhead depicts mitotic hepatocytes. Data represent mean ± SEM. One-way ANOVA with Tukey’s correction; *P < 0.05, **P < 0.01, ***P < 0.001. White bars denote WT mice fed chow diet; gray bars denote old Acox1^Lampe1 mice fed chow diet; black bars denote young Acox1^Lampe1 mice fed HFHCD. A single experiment, n = 3/condition.