Extended Data Fig. 4: Hepatotoxicity of a dominant negative LXRα mutation in mice fed a low fat diet.
8-week-old LXRα+/+ (Wt, N = 13), LXRα+/W441R (Het, N = 15) and LXRαW441R/W441R (Hom, N = 11) mice were placed on a low fat (12% by Kcal), high-sucrose (34.1% by weight) diet for 8 weeks when mice were euthanised and blood and tissues were collected for downstream analyses. A: Body weight curves (mean and 95% confidence intervals). B-C: Lean and fat mass determined by Echo MRI at 16 weeks of age. D-G: Serum biochemistry from terminal bleeds, in (G) Total cholesterol is separated into HDL and non-HDL fractions, ****P < 0.0001, HDL cholesterol, **P = 0.001 non-HDL cholesterol. H:Tissue weights, I-K: lipid measurements in liver lysate normalized to liver weight. L-O: Immunohistochemical staining for indicated markers was performed and quantified using HALO image analysis platform (Indica labs). Representative images of H&E staining are shown in (P). Livers were stained for collagen using picrosirius red (PSR) stain and quantified by HALO (Q). Representative images of PSR staining are shown in (R). A: Body weight curves were compared by mixed-effects model was used with post hoc Holm-Šídak test. B-O, Q: Analysis was performed using Kruskal–Wallis test with Dunn’s multiple comparison test or ordinary one-way ANOVA with Holm-Šídak multiple comparison, based on the distribution of the data. Comparisons were made between Wt and Het and Wt and Hom, only P < 0.05 are detailed. All reported P values are two-sided. All data are presented as mean ± SD, except Panel G, where mean ± SEM is represented.
