A high-energy diet increases hepatic mitochondrial proteins and transcripts related to fatty acid oxidation and ketogenesis, and training partially mitigates this effect. A–C: Significantly different proteins in the liver mitochondrial proteome when comparing (A) sedentary HED-fed and sedentary control-fed mice (HED_SED/CON_SED), (B) trained HED-fed and trained control-fed mice (HED_TRAIN/CON_TRAIN), and (C) trained and sedentary HED-fed mice. Data points were colored based on enriched categories of STRING pathways and are plotted by p-values (according to Student's t-test, no correction for multiple testing) versus fold changes between groups. Green = fatty acid oxidation, red = peroxisome, orange = respiratory chain, purple = pyruvate metabolism, light gray = endoplasmic reticulum and ribosomes, and blue = ketogenesis. (A, B: only proteins with fold change <0.85 or >1.15 were colored). See also Table S2. STRING: Search Tool for the Retrieval of Interacting Genes/Proteins. D, E: Significantly different proteins (according to Student's t-test, no correction for multiple testing) related to fatty acid oxidation and ketogenesis in trained or sedentary HED- or control-fed mice. Values were centered to the mean of the respective protein and scaled to unit variance. White color shows values close to the mean and red- and blue-colored values are higher and lower, respectively than the mean. Each column represents one animal; n = 8 per group. ns: not significant. F, G: Transcripts encoding proteins of fatty acid oxidation or ketogenic enzymes increased with HED in mouse liver tissues. CON = control diet, HED = high-energy diet, SED = sedentary, TRAIN = treadmill training. n = 6–8, mean ± SD. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001 for diet, training or interaction by 2-way ANOVA as indicated. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001 for diet by Tukey HSD multiple comparisons test.