| First Author | Sanderson LM | Year | 2010 |
| Journal | Physiol Genomics | Volume | 41 |
| Issue | 1 | Pages | 42-52 |
| PubMed ID | 20009009 | Mgi Jnum | J:157961 |
| Mgi Id | MGI:4437399 | Doi | 10.1152/physiolgenomics.00127.2009 |
| Citation | Sanderson LM, et al. (2010) Transcriptional profiling reveals divergent roles of PPARalpha and PPARbeta/delta in regulation of gene expression in mouse liver. Physiol Genomics 41(1):42-52 |
| abstractText | Little is known about the role of the transcription factor peroxisome proliferator-activated receptor (PPAR) beta/delta in liver. Here we set out to better elucidate the function of PPARbeta/delta in liver by comparing the effect of PPARalpha and PPARbeta/delta deletion using whole genome transcriptional profiling and analysis of plasma and liver metabolites. In fed state, the number of genes altered by PPARalpha and PPARbeta/delta deletion was similar, whereas in fasted state the effect of PPARalpha deletion was much more pronounced, consistent with the pattern of gene expression of PPARalpha and PPARbeta/delta. Minor overlap was found between PPARalpha- and PPARbeta/delta-dependent gene regulation in liver. Pathways upregulated by PPARbeta/delta deletion were connected to innate immunity and inflammation. Pathways downregulated by PPARbeta/delta deletion included lipoprotein metabolism and various pathways related to glucose utilization, which correlated with elevated plasma glucose and triglycerides and reduced plasma cholesterol in PPARbeta/delta-/- mice. Downregulated genes that may underlie these metabolic alterations included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent novel PPARbeta/delta target genes. In contrast to PPARalpha-/- mice, no changes in plasma free fatty acid, plasma beta-hydroxybutyrate, liver triglycerides, and liver glycogen were observed in PPARbeta/delta-/- mice. Our data indicate that PPARbeta/delta governs glucose utilization and lipoprotein metabolism and has an important anti-inflammatory role in liver. Overall, our analysis reveals divergent roles of PPARalpha and PPARbeta/delta in regulation of gene expression in mouse liver. |
