Figure 1.

Megamitochondria are formed in mouse MCD diet model and human patients with NASH

(A) Liver sections from the indicated NASH mouse models were analyzed by Oil Red O staining for steatosis, H&E (H&E) staining for lobular inflammation, and Sirius Red staining for fibrosis. Boxed regions are enlarged.

(B–D) Quantification of steatosis in (B), lobular inflammation in (C), and fibrosis in (D) are shown. Bars are average ± SD (n = three to four mice).

(E) Heatmap summary of histopathology and mitochondrial size.

(F) Cryosections of livers from the indicated NASH mouse models were subjected to laser confocal immunofluorescence microscopy using antibodies to a mitochondrial protein, pyruvate dehydrogenase (PDH). Boxed regions are enlarged.

(G) Quantification of mitochondrial size. Bars are average ± SD for n = 500–600 mitochondria for each experimental group.

(H) Histological scoring of liver sections from human patients using the NASH Clinical Research Network scoring system (Kleiner et al., 2005).

(I) Mitochondria were visualized by immunofluorescence microscopy with anti-PDH antibodies in the same set of human patients with NASH described in (H). Boxed regions are enlarged.

(J) Quantification of mitochondrial size. Bars are average ± SD (n = 203 for control subject 1, 215 for control subject 2, 178 for NASH subject 1, 170 for NASH subject 2). Statistical analysis was performed using Student’s t test in (B, C, D, and G; Std 6w and MCD 6w) and one-way ANOVA with post-hoc Dunnett’s test in (B, C, D, and G; Std 24w and other diets 24w): ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.