Charaterization of potential roles and mechanisms of ACBP/DBI in NASH/MASH-dirven HCC mouse models

We demonstrated that ACBP/DBI inhibition impaired hepatocarcinogenesis in NASH/MASH-driven HCC models. To further investigate its potential mechanisms at transcriptional level in NASH/MASH-driven HCC models, we performed Bulk RNA-seq analyses with liver tissues from the following three models, namely, (i) WD/CCl4 with tamoxifen inducible ACBP/DBI knout mice (Dbi-/- mice, Dbi+/+ mice as control) for in total 27 weeks; (ii) WD/CCl4 with KLH/KLH-ACBP immunized mice for in total 34 weeks; and (iii) HFD/DEN with KLH/KLH-ACBP immunized miceI for a total of 36 weeks. Overall design: (i) WD+CCl4 with Dbi+/+ and Dbi-/- mice, tamoxifen was i.p.injected with a dose of 75 mg/kg/day, for 5 consecutive days. After 3 days, mice received a western diet, high-sugar water (23.1 g/L D-fructose plus 18.9 g/L D-glucose), and weekly i.p. injections of carbon tetrachloride (CCl4) for 26 weeks; (ii)WD/CCl4 with KLH/KLH-ACBP immunized mice, the 5-week old mice were i.p. vaccinated with the mixture of KLH/Montanide or KLH-ACBP/Montanide on days 0 (30 µg), 7 (30 µg), 14 (30 µg), and 21 (10 µg of KLH-ACBP) to induce anti-ACBP autoantibodies, then mice received a western diet, high-sugar water (23.1 g/L D-fructose plus 18.9 g/L D-glucose), and weekly i.p. injections of carbon tetrachloride (CCl4) for 30 weeks; (iii)HFD/DEN with KLH/KLH-ACBP immunized mice, mice (15 dpp) were treated with a single dose of diethylnitrosamin (DEN) dissolved in saline at a dose of 25 mg/kg body weight by i.p. injectionthe, after 2 weeks, mice started the KLH/KLH-ACBP vaccination plus HFD for 34 weeks. All mice in the above mouse models are male, C57BL/6 background. Four to five samples are incuded in each treatment group.