Transcriptional profiling reveals divergent roles of PPARa and PPARß/d in regulation of gene expression in mouse liver
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ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE17865
PROVIDER: PRJNA120111 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description: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.
2010-06-21 | E-GEOD-17863 | biostudies-arrayexpress
Project 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. Keywords: Analysis of target gene regulation by using microarrays
2009-10-12 | GSE17863 | GEO
Project 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. Keywords: Analysis of target gene regulation by using microarrays
2009-12-29 | GSE17864 | GEO
Project description:Fenofibrate is a specific agonist of the nuclear receptor PPARa. To identify the gene expression 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. We used microarrays to detail the global programme of gene expression in liver of Ppara LKO, LWT, Ppara KO and WT male mice. There are 36 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 14 week-old from the same genetic background (C57Bl/6J) treated with Fenofibrate (100 mg/kg/day) or vehicle (aqueous solution of gum Arabic 3%) by daily gavage for 10 days. n= 4 mice for LKO, LWT and WT genotypes treated with vehicle; n=3 for KO mice treated with vehicle; n=5 mice for LWT, LKO and KO genotypes treated with fenofibrate; n=4 WT mice treated with fenofibrate. All mice were sacrified at ZT14.
2016-02-20 | E-GEOD-73298 | biostudies-arrayexpress
Project description:Fenofibrate is a specific agonist of the nuclear receptor PPARa. To identify the gene expression 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. We used microarrays to detail the global programme of gene expression in liver of Ppara LKO, LWT, Ppara KO and WT male mice.
2016-02-20 | GSE73298 | GEO
Project description:To clarify the mechanism underlying the proliferation of hepatocytes induced by PPARA agonists, expression profiling in liver of wild type and Ppara-null mice treated with PPARA agonist was investigated.
2022-04-05 | GSE154275 | GEO
Project description: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.
2016-02-20 | E-GEOD-73299 | biostudies-arrayexpress
Project description: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.
2016-02-20 | GSE73299 | GEO
Project description:Expression data from Ppara (peroxisome proliferator activated receptor alpha) KO mice injected with TFEB specifically in liver. In order to identify the effects of TFEB overexpression together with Ppara absence on the liver transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the injected mice For the analysis on the injected Ppara-KO mice overexpressing TFEB, total RNA was extracted from the liver of three mice; RNA extracted from the liver of not-injected mice was used as control.
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Project description:To identify genes whose expression is under the strict dependence of hepatocyte PPARa activity, we used a mouse strain of PPARa-specific deletion in hepatocyte (albumin-Cre+/- Pparaflox/flox or LKO) and we compared them to their liver WT littermates (albumin-Cre-/- Pparaflox/flox or LWT) fed ad libitum or fasted for 24 hours.
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