Figure 2.

Insig1 ablation improved the lipidome and reduced cellular damage, inflammation, and extracellular matrix deposition in a Western diet supplemented with sugar water. (A) Relative Insig1 mRNA expression measured by RTqPCR. (B) NGS showing upregulation of key enzymes in lipid/cholesterol synthesis, remodelling, and oxidation. (C) Relative Fasn mRNA expression measured by RTqPCR. DNL-like triglycerides (D) and phosphatidylcholine (E) as measured by LC-MS. (F) Relative Scd1 mRNA expression as measured by RTqPCR. Monounsaturated fatty acid-containing triglycerides (G) and phosphatidylcholines (H). (I) Prediction of canonical pathways significantly enriched and predicted as activated (orange) or inhibited (green) according to IPA; data are shown as a heat map matrix format representing the prediction of activation (Z score). HALO imaging software analysis on scanned slides of whole tissue of: (J) caspase 3 IHC, (K) F4/80 IHC, (L) CD45R IHC, (M) CD3 IHC, and (N) Picrosirius Red. Representative tissues are shown. (O) Gene expression of selected genes involved in apoptosis, autophagy, compensatory hepatocyte proliferation, inflammation, hepatic stellate cell (HSC) activation and fibrosis, and epithelial–mesenchymal transition (EMT) as profiled by NGS. Data were analysed by ANOVA (p values < 0.05 are considered significant) with Tukey's post hoc test (a, reference group; groups with different letters are statistically different per post hoc comparison; differences between groups with the same letter are statistically not significant per post hoc comparison). NGS data were analysed with the Wald test (#p < 0.05 and ∗p_BH < 0.05). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)