Fig. 5: Obese Lyz-IFNγR2^−/− mice are protected from liver fibrosis but not steatosis after the GAN diet.

Noninvasive ultrasound imaging and histological analyses were performed to assess MASH phenotypes in male Lyz-IFNγR2^−/− and WT mice during 20 weeks of the Gubra Amylin NASH (GAN) diet starting at 6 months of age (n = 7 per genotype). A Body weight changes during 20 weeks of the GAN diet. B Liver steatosis as shown in brightness during 20 weeks of the GAN diet. C Liver fibrosis as stiffness using Young’s Modulus during 20 weeks of the GAN diet (n = 6 WT and 7 Lyz-IFNγR2^−/− mice). D Representative SWE images showing shear wave elasticity in regions of high and low intensity in GAN diet-fed mice. E Liver samples collected after 20 weeks of the GAN diet were processed for hematoxylin & eosin (H&E) and Masson’s Trichrome stain, and histology slides were evaluated by a board-certified pathologist (Applied Pathology Systems). MASLD activity score (MAS) was calculated for individual Lyz-IFNγR2^−/− and WT mice (n = 3 per genotype) by combining the histology scoring for lobular inflammation, macro-vesicular steatosis, and ballooning. F Representative histology images showing lobular and portal inflammation, and pericellular, bridging, and cirrhotic nodular fibrosis in WT2 mouse. Histology images showing lobular inflammation and pericentral fibrosis in KO1 mouse. Data are presented as mean ± SEM values. The statistical significance of the difference in mean values between Lyz-IFNγR2^−/− mice versus WT mice at each time point (weeks of GAN diet) was determined using a two-tailed Student’s t-test. The statistical significance of the difference in mean values between 8, 12, 16, and 20 weeks of GAN diet versus 4 weeks was determined using a one-way analysis of variance (ANOVA) with Tukey’s multiple comparison test for post-hoc analysis.