Figure 6

Global decreases in mitochondrial gene expression in PPARα-null mice after heat shock are prevented by WY pretreatment. A. Down-regulation of genes regulated by the co-activator PGC-1. Gene Set Enrichment Analysis (GSEA) was used to identify gene sets that exhibited significant overlaps with those gene differences between control and HS in PPARα-null mice. Left, enrichment plot for genes regulated by PGC-1. Black bars illustrate the position of probe sets belonging to the PGC-1 gene set in the context of all probes on the U74Av2 array. The running enrichment score (RES) plotted as a function of the position within the ranked list of array probes is shown as a green line. The ranked list metric shown in gray illustrates the correlation between the signal to noise values of all individually ranked genes according to the class labels (experimental conditions). Right, individual expression profiles for leading edge probe sets contributing to the normalized enrichment score are shown. Signal intensities are illustrated by varying shades of red (up-regulation) and blue (down-regulation). B. Prevention of down-regulation of electron transporter gene expression by pretreatment with WY. Left, enrichment plot for genes with electron transporter activity as described in A. Right, individual expression profiles for probe sets contributing to the normalized enrichment score are shown. C. Increased expression of PGC1β and regulated genes involved in lipid homeostasis by WY in PPARα-null mice. GSEA-derived heat map of the top 100 differentially expressed probe sets enriched in the control or WY-treated groups from PPARα-null mice. Location of PGC1β (Ppargc1b) and regulated genes are indicated. D. Increased expression of genes involved in fatty acid metabolism after exposure to WY for 5 days in PPARα-null mice. Genes significantly altered in the GSEA set "fatty acid metabolism" are shown. These include a number that overlap with those that are involved in mitochondrial fatty acid metabolism regulated by PGC-1.