Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Global hepatic gene expression data from PPARa liver KO, PPARa liver WT, PPARaKO and WT male mice fed ad libitum, fasted for 24 hours and re-fed

ABSTRACT: If the function of the nuclear receptor PPARa is well-known during a prolongated fasting, its hepatic biological function during feeding and refeeding conditions still needs to be investigated. Moreover, in vivo data collected so far on PPARa function during fasting were obtained using the total Ppara KO transgenic mouse model. To identify genes whose expression is under the strict dependence of hepatic PPARa activity, we generated a new mouse strain of PPARa-specific deletion in hepatocyte (albumin-Cre+/- Pparaflox/flox or LKO) and we compared them to total Ppara KO (KO), wild-type (WT) and liver WT (albumin-Cre-/- Pparaflox/flox or LWT) mice under three nutritional challenges. We used microarrays to detail the global programme of gene expression in liver of Ppara LKO, LWT, Ppara KO and WT male mice fed ad libitum, fasted for 24 hours and refed. There are 52 liver samples, each from an individual mouse. The samples are from Ppara liver KO (LKO), Ppara KO (KO), wild-type (WT) and liver WT (LWT) male mice of 8 week-old from the same genetic background (C57Bl/6J) fed ad libitum, fasted for 24 hours, fasted for 24 hours and then refed 24 hours more with glucose added in water (200g/l). In fed condition (Fed), n= 3 mice for LKO, LWT genotypes, n= 5 for KO and n= 4 fot WT; in fasting condition (Fas), n=5 for LKO, LWT and WT genotypes and n= 3 for KO; in refeeding condition (Ref), n= 5 for LKO, KO and WT genotypes and n= 4 for LWT. All mice were sacrified at ZT14.

ORGANISM(S): Mus musculus

SUBMITTER: Alexandra Montagner

PROVIDER: E-GEOD-73299 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD.

Montagner Alexandra A Polizzi Arnaud A Fouché Edwin E Ducheix Simon S Lippi Yannick Y Lasserre Frédéric F Barquissau Valentin V Régnier Marion M Lukowicz Céline C Benhamed Fadila F Iroz Alison A Bertrand-Michel Justine J Al Saati Talal T Cano Patricia P Mselli-Lakhal Laila L Mithieux Gilles G Rajas Fabienne F Lagarrigue Sandrine S Pineau Thierry T Loiseau Nicolas N Postic Catherine C Langin Dominique D Wahli Walter W Guillou Hervé H

Gut 20160201 7

<h4>Objective</h4>Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor expressed in tissues with high oxidative activity that plays a central role in metabolism. In this work, we investigated the effect of hepatocyte PPARα on non-alcoholic fatty liver disease (NAFLD).<h4>Design</h4>We constructed a novel hepatocyte-specific PPARα knockout (Pparα(hep-/-)) mouse model. Using this novel model, we performed transcriptomic analysis following fenofibrate treatment. Next, we inves ...[more]

PMID: 26838599

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Project description:Little is known about the role of the transcription factor PPARÃ?/d in liver. Here we set out to better elucidate the function of PPARÃ?/d in liver by comparing the effect of PPARa and PPARÃ?/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 PPARÃ?/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 PPARÃ?/d. Minor overlap was found between PPARa- and PPARÃ?/d-dependent gene regulation in liver. Pathways upregulated by PPARÃ?/d deletion were connected to innate immunity. Pathways downregulated by PPARÃ?/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 PPARÃ?/d-/- mice. Downregulated genes that may underlie these metabolic alterations included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent novel PPARÃ?/d target genes. In contrast to PPARa-/- mice, no changes in plasma FFA, plasma Ã?-hydroxybutyrate, liver triglycerides and liver glycogen were observed in PPARÃ?/d-/- mice. Our data indicate a role for PPARÃ?/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 PPARÎ± -/- 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 -80ÂºC until further analysis. For RNA analyses, tissue from the same part of the liver lobe was used.

Dataset Information

Global hepatic gene expression data from PPARa liver KO, PPARa liver WT, PPARaKO and WT male mice fed ad libitum, fasted for 24 hours and re-fed

Publications

Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD.

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