Figure 1

High-fat diet and calorie restriction alter body mass and induce extensive hepatic transcriptional changes. (A) HFD and CR feeding increase and decrease overall mouse body mass, respectively, compared to CD (n = 12, 10, and 12 for CD, HFD, and CR, ***p < 5e-5, two-sided t-tests). (B–D) HFD induces insulin resistance and alters glycemic regulation as assessed by (B) glucose tolerance test (GTT), (C) insulin tolerance test (ITT), and (D) pyruvate tolerance test (PTT) (p-values from t-tests of area under the curve measurements, n = 30, 25, and 23 for CD and n = 37, 27, and 23 for HFD). (E) Venn diagrams show numbers of genes differentially expressed between CD and HFD livers (red circle) as well as CD and CR livers (blue circle). The overlap region shows 695 genes that are differentially expressed in both CR and HFD compared to CD. The clustergram shows these 695 overlapping genes that are up-regulated by both HFD and CR (255 genes), down-regulated by both CR and HFD (183 genes), up-regulated in HFD and down-regulated by CR (186 genes), and up-regulated in CR but down-regulated in HFD (71 genes), along with gene ontology and pathway enrichment terms. The numbers indicate how many genes in each group that are annotated to each term. Values are log₂ fold-changes for individual replicate expression levels (in FPKM) versus the mean CD expression level. (F) 3,901 genes are differentially expressed between CR and HFD livers (green circle). The clustergram shows individual replicate gene expression levels as log₂ fold-change compared to the mean expression level for the opposite condition (CR or HFD). The numbers indicate how many genes in each group that are annotated to each term.