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

Dataset

Description

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 available29 Dec 2009
PublisherWageningen University

Research Output

Transcriptional profiling reveals divergent roles of PPARa and PPARß/d in regulation of gene expression in mouse liver

Sanderson, L., Boekschoten, M. V., Desvergne, B., Müller, M. R. & Kersten, A. H., 2010, In : Physiological genomics. 41, 1, p. 42-52

Research output: Contribution to journalArticleAcademicpeer-review

  • 80 Citations (Scopus)

    Cite this

    Sanderson-Kjellberg, L. M. (Creator), Boekschoten, M. (Creator), Desvergne, B. (Creator), Muller, M. (Creator), Kersten, S. (Creator) (29 Dec 2009). mRNA profiling reveals divergent roles of PPARa and PPARß/d in regulating mouse liver gene expression (PPARb/d samples). Wageningen University.