The Sense Of CASK

In particular, fatty acid metabolism, androgen and estrogen metabolism, biosynthesis of steroids, pyruvate metabolism, and PPAR signaling pathway were significantly deregulated in the liver of Rap1-deficient females. In gonadal white fat, Rap1-deficient mice showed an enrichment of inflammation/immunity and cell adhesion/cell-cell interaction networks ( Figure?S3B; VX-809 solubility dmso Table S3). Similarly, metabolic pathways, such as OXPHOS and PPAR signaling pathways, also showed an enriched signature in wild-type gonadal fat ( Figure?S3B; Table S3). In contrast, GSEA of muscle did not render any significantly deregulated pathway, suggesting that the RAP1-mediated metabolic phenotype does not stem from transcriptional deregulation in muscle (data not shown). In agreement with this notion, we did not find differences in the abundance of type I (high oxidative potential) and type II (low oxidative potential) fibers in the gastrocnemius muscle CASK ( Lin et?al., 2002). We also found a similar succinate dehydrogenase (SDH) staining in the gastrocnemius of young females (8?weeks old) from both genotypes ( Figures S2D and S2E), thus indicating that metabolic phenotypes associated with Rap1 deficiency are not mediated by the muscle. We further confirmed deregulation of key metabolic pathways in older females at the onset of obesity by using both transcriptome and proteome analyses (Experimental Procedures). In particular, we studied wild-type and Rap1-deficient females at 34?weeks of age, with mean body weights of 24 and 36 g, respectively. Differential gene expression analysis revealed that 671 probes deregulated, corresponding to 618 genes (false discovery rate [FDR] this website in Rap1-deficient livers ( Table S5). In addition, GSEA of Rap1-deficient livers showed alteration of many metabolic pathways, including the branched chain amino acid degradation, the PPAR signaling pathway, glycerolipids, and fatty acid metabolism, which showed a highly significant enrichment in Rap1-deficient livers (FDR