Fig. 2.

Liver-specific loss of p53 accelerates diet-induced MASH.

(A) Representative liver H&E images and staining for p21, lipid content (ORO), lipid peroxidation (MDA), fibrosis (PSR), and macrophages (F4/80) in male Albumin-Cre+; Trp53 WT (Trp53^WT) and Albumin-Cre+; Trp53^FL/FL (Trp53^livΔ) mice after 1 year on control chow diet or obesogenic HFHS diet. ORO images are representative of n = 4 Trp53^WT chow-fed mice, n = 3 Trp53^livΔ chow-fed mice and n = 3 HFHS-fed mice per genotype; scale bars 40 μm. For the remainder, representative of n = 9 Trp53^WT chow-fed mice, n = 8 Trp53^livΔ chow-fed mice and n = 13 HFHS-fed mice per genotype. Scale bars 20 μm. Arrows denote p21-positive hepatocytes or F4/80-positive macrophage-engulfed hepatocytes (lipogranulomas). (B-E) Quantification of p21-positive hepatocytes per field (B), ORO stain area (C), MDA-positive stain area (D), PSR stain area (E), and F4/80-positive lipogranulomas per field (F) in mice from (A). WT: Trp53^WT, FL: Trp53^livΔ. N-numbers as in (A). Data presented as mean +/- SEM and analysed using two-way ANOVA with Holm-Sidak’s multiple comparisons test and multiplicity-adjusted p values. n.s., not significant, ∗p <0.05, ∗∗p <0.01, ∗∗∗p <0.001, ∗∗∗∗p <0.0001. HFHS, high-fat and high-sugar; MDA, malondialdehyde; ORO, Oil red O; PSR, Picrosirius red; ROS, reactive oxygen species; WT, wild-type.