Hepatic inflammation, fibrosis, and oxidative stress in Ts65Dn male mice fed a high-fat diet. A) Liver weight of male mice (% of body weight). B) Representative H&E stained liver sections of male Ts65Dn and euploid mice. The quantifications of lipid area in male (Euploid, n = 14; Ts65Dn, n = 8) are indicated by the bar graph. C) Liver weight of female mice (% of body weight). D) Representative H&E stained liver sections of female Ts65Dn and euploid mice. The quantifications of lipid area in female (Euploid, n = 11; Ts65Dn, n = 8) mice are indicated by the bar graph. E) Volcano plot of the liver RNA-seq data. The dotted y-axis line shows the adjusted p-value cut-off for significance (adj. p-value = 0.05). The two dotted x-axis lines represent a Log2(FC) of −0.5 or 0.5. A total of 336 out of 20,680 genes (1.62% of the liver transcriptome) are differentially expressed in male Ts65Dn mice relative to euploid controls, with 175 genes upregulated and 161 genes downregulated. PCG, protein coding genes; NPCG, non-protein coding genes. F) The table shows the top 20 up- and down-regulated genes. G) The top 20 most significant Gene Ontology (GO) and KEGG categories based on differentially expressed genes (DEGs) seen in the liver of Ts65Dn. The stalk color represents the category the title belongs to (KEGG pathway, MF = molecular function, BP = biological process, CC = cell component). The size of the circle represents how many genes (or counts) are altered in the group. The color of the circle represents the direction of change, and the magnitude of the gene ratio. A high gene ratio means more genes in that gene family are affected in this group. H) Heat maps of genes associated with inflammation and fibrosis. The size of the box indicates statistical significance in trisomic gene expression between male Ts65Dn mice relative to euploid controls. Full-size box denotes significantly different expression (adjusted p-value ≤0.05), medium size box denotes significantly different expression (non-adjusted p-value ≤0.05), and small box size denotes non-significant expression between genotypes (p-value >0.05). The color gradient indicates Log2(FC) of each gene in Ts65Dn relative to euploid controls, with upregulated genes in the red and downregulated genes in the blue color spectrum. Tissue sample size for liver RNA sequencing (Euploid, n = 6; Ts65Dn, n = 6).