Fig. 3.

Loss of liver p53 is lethal in leptin-deficient (Lep^ob/ob) obese mice. (A) Representative liver H&E images and staining for MDA, PSR, and F4/80 in Albumin-Cre+; Lep^ob/ob; Trp53 WT (ob/ob; Trp53^WT) (n = 14 total: n = 8 male and n = 6 female) and Albumin-Cre+; Lep^ob/ob; Trp53^FL/FL (ob/ob; Trp53^livΔ) (n = 10 total: n = 4 male and n = 6 female) mice. ob/ob; Trp53^livΔ mice were sampled when reaching endpoint due to clinical signs of moderate severity. Of these, n = 5/10 had liver tumours that were confirmed by histology and n = 5/10 had small tumours or lacked macroscopic tumour burden, as reflected in downstream analyses. ob/ob; Trp53^WT mice were all healthy at endpoint and sampled at timepoints consistent with the observed survival of ob/ob; Trp53^FL/FL mice, in a time range from 269-323 days of age. Macrophage-engulfed steatotic hepatocytes (lipogranulomas) depicted by arrows. Scale bars 20 μm. (B-E) Quantification of liver images from (A), including MDA-positive stain area (B), PSR stain area (C), F4/80-positive lipogranulomas per field (D), and total F4/80-positive staining (E) in mice from (A). WT: ob/ob; Trp53^WT, FL: ob/ob; Trp53^livΔ. N-numbers as in (A). Data presented as mean +/- SEM and analysed using an ordinary one-way ANOVA and 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. Liv, liver; MDA, malondialdehyde; PSR, Picrosirius red; Tum, tumour; WT, wild-type.