Figure legends
Figure 1. (a) Study design. (b) Body
weight development over the intervention period. (c)
Food intake over the course of the study. ***p<0.001 vs
DIO-NASH vehicle control.
Figure 2. Systemic safety and metabolic parameters.
(a) Plasma ALT, (b) plasma AST
activities. (c) Plasma total cholesterol,
(d) plasma triglycerides, (e) 4-hour
fasting blood glucose and (f) plasma insulin levels.
(a) -(d) were measured at study
termination, (e) and (f) on study day
39. *p<0.05, **p<0.01, ***p<0.001 vs
DIO-NASH vehicle control.
Figure 3. Liver weight, hepatic lipid, collagen and
α-smooth muscle actin (α-SMA) content at study termination.
(a) Wet liver weight, (b) hepatic
triglycerides, (c) hepatic total cholesterol.
(d) Total liver lipid content, (e)
hepatic collagen 1a1 and (f) liver α-SMA determined by
histology and quantitative image analysis. **p<0.01,
***p<0.001 vs. DIO-NASH vehicle control.
Figure 4. (a) Representative images of liver
morphology at termination of the study. H&E staining (20x, scale bar =
100 µm), (b) Picrosirius Red staining (20x, scale bar =
100 µm). (c) Change in NAFLD activity score (pre- vs.
post-treatment) for individual animals in the different treatment
groups: Lean control mice (grey), DIO-NASH vehicle controls (black) and
DIO-NASH mice treated with resmetirom (orange), (d)
Change in fibrosis stage as above. N=10-11 per group, **p<0.01
vs DIO-NASH vehicle group (One-sided Fisher’s exact test with Bonferroni
correction).
Figure 5. Hepatic gene expression assessed by RNA
sequencing with subsequent Ingenuity pathway analysis:
(a) principal component analysis over all 53431 measured
transcripts displaying the first two main components, PC1 and PC2.
(b) Visualization of upstream factor analysis performed
with Ingenuity, which predicts THR-ß as one important factor activated
in the resmetirom treated group. (c-e) Expression of
selected genes in normalized counts (FKPM) and shown as box-whisker
blots with median (line) and mean (+) and confidence intervals of 5% to
95%. *p<0.05, **p<0.01, *p<0.001 vs
DIO-NASH vehicle group (false-discovery rate adjusted for multiplicity
by Benjamini-Hochberg correction).