Fig. 6
Dietary intervention improves markers of hepatic mitochondrial function in GAN DIO-NASH mice. A Maximal liver mitochondrial respiratory capacity assessed via high-resolution respirometry (O2 flux/mg tissue/second). Maximal respiration after the addition of substrates stimulating complex I of the electron transport system (ETS; Respiration-Complex I). Maximal respiration after the addition of substrates stimulating both complex I and II of the electron transport chain (Respiration-Complex I + II). Maximal uncoupled respiration after the addition of uncoupling agent FCCP (Respiration-ETS). B Spectrophotometrically determined mitochondrial enzyme activity (µmol/g tissue/minute) of enzymes Beta-hydroxyacyl-CoA dehydrogenase (β-HAD) and citrate synthase. Mean ± SEM. **p < 0.01 compared to Chow vehicle; #p < 0.05, ##p < 0.01, ###p < 0.001 compared to corresponding vehicle-dosed GAN DIO-NASH mouse group. Dunnett’s test one-factor linear model. C-D RNA sequencing analysis. C Heatmap illustrating changes in expression of genes related to mitochondrial fatty acid oxidation after 8-24 weeks in vehicle-dosed GAN DIO-NASH mice receiving chow reversal as compared to chow controls. D Heatmap illustrating changes in expression of genes related to mitochondrial fatty acid oxidation after 8-24 weeks of chow reversal as compared to corresponding GAN DIO-NASH vehicle control group. Color gradients in heatmaps indicate significantly upregulated (red color) or downregulated (blue color) gene expression (log2-fold change, false discovery rate p < 0.05). Unregulated genes are indicated without color fill (white color)