Unknown,Transcriptomics,Genomics,Proteomics

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MRNA profiling reveals divergent roles of PPARa and PPARÃ?/d in regulating mouse liver gene expression (PPARa samples)


ABSTRACT: Little is known about the role of the transcription factor PPAR�/d in liver. Here we set out to better elucidate the function of PPAR�/d in liver by comparing the effect of PPARa and PPAR�/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 PPAR�/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 PPAR�/d. Minor overlap was found between PPARa- and PPAR�/d-dependent gene regulation in liver. Pathways upregulated by PPAR�/d deletion were connected to innate immunity. Pathways downregulated by PPAR�/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 PPAR�/d-/- mice. Downregulated genes that may underlie these metabolic alterations included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent novel PPAR�/d target genes. In contrast to PPARa-/- mice, no changes in plasma FFA, plasma �-hydroxybutyrate, liver triglycerides and liver glycogen were observed in PPAR�/d-/- mice. Our data indicate a role for PPAR�/d in hepatic glucose utilization and lipoprotein metabolism but not in the adaptive response to fasting. Keywords: Analysis of target gene regulation by using microarrays Pure-bred Sv129 PPARα -/- mice and corresponding wildtype mice were used. Male mice (n=4-5 per group) were either fed or fasted for 24 hours. At the end of the experiment, mice were anaesthetized with a mixture of isofluorane (1.5%), nitrous oxide (70%) and oxygen (30%). Blood was collected by orbital puncture, after which the mice were sacrificed by cervical dislocation. Livers were dissected, snap frozen in liquid nitrogen and kept at -80ºC until further analysis. For RNA analyses, tissue from the same part of the liver lobe was used.

ORGANISM(S): Mus musculus

SUBMITTER: Guido Hooiveld 

PROVIDER: E-GEOD-17863 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) but not PPARalpha serves as a plasma free fatty acid sensor in liver.

Sanderson Linda M LM   Degenhardt Tatjana T   Koppen Arjen A   Kalkhoven Eric E   Desvergne Beatrice B   Müller Michael M   Kersten Sander S  

Molecular and cellular biology 20091005 23


Peroxisome proliferator-activated receptor alpha (PPARalpha) is an important transcription factor in liver that can be activated physiologically by fasting or pharmacologically by using high-affinity synthetic agonists. Here we initially set out to elucidate the similarities in gene induction between Wy14643 and fasting. Numerous genes were commonly regulated in liver between the two treatments, including many classical PPARalpha target genes, such as Aldh3a2 and Cpt2. Remarkably, several genes  ...[more]

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