mRNA profiling reveals divergent roles of PPARa and PPARß/d in regulating mouse liver gene expression (PPARa samples)



Little is known about the role of the transcription factor PPARß/d in liver. Here we set out to better elucidate the function of PPARß/d in liver by comparing the effect of PPARa and PPARß/d deletion using whole genome transcriptional profiling and analysis of plasma and liver metabolites. In fed state, the number of genes altered by PPARa and PPARß/d deletion was similar, whereas in fasted state the effect of PPARa deletion was much more pronounced, consistent with the pattern of gene expression of PPARa and PPARß/d. Minor overlap was found between PPARa- and PPARß/d-dependent gene regulation in liver. Pathways upregulated by PPARß/d deletion were connected to innate immunity. Pathways downregulated by PPARß/d deletion included lipoprotein metabolism and various pathways related to glucose utilization, which correlated with elevated plasma glucose and triglycerides and reduced plasma cholesterol in PPARß/d-/- mice. Downregulated genes that may underlie these metabolic alterations included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent novel PPARß/d target genes. In contrast to PPARa-/- mice, no changes in plasma FFA, plasma ß-hydroxybutyrate, liver triglycerides and liver glycogen were observed in PPARß/d-/- mice. Our data indicate a role for PPARß/d in hepatic glucose utilization and lipoprotein metabolism but not in the adaptive response to fasting.
Date made available12 Oct 2009
PublisherWageningen University

Research Output

Peroxisome Proliferator-Activated Receptor ß/ (PPARß/) but Not PPAR Serves as a Plasma Free Fatty Acid Sensor in Liver

Sanderson, L., Degerhardt, T., Desvergne, B., Koppen, A., Kalkhoven, E., Müller, M. R. & Kersten, A. H., 2009, In : Molecular and Cellular Biology. 29, 23, p. 6257-6267

Research output: Contribution to journalArticleAcademicpeer-review

Open Access
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    Sanderson-Kjellberg, L. M. (Creator), Boekschoten, M. (Creator), Desvergne, B. (Creator), Muller, M. (Creator), Kersten, S. (Creator) (12 Oct 2009). mRNA profiling reveals divergent roles of PPARa and PPARß/d in regulating mouse liver gene expression (PPARa samples). Wageningen University.