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GSE17864
Mus musculus
16 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
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.
Publication Title
Transcriptional profiling reveals divergent roles of PPARalpha and PPARbeta/delta in regulation of gene expression in mouse liver.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 92 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Dietary fatty acids have myriads of effects on human health and disease. Many of these effects are likely achieved by altering expression of genes. Several transcription factors have been shown to be responsive to fatty acids, including SREBP-1c, NF-kB, RXRs, LXRs, FXR, HNF4, and PPARs. However, the relative importance of these transcription factors in regulation of gene expression by dietary fatty acids remains unclear. Here, we take advantage of a unique experimental design using synthetic triglycerides composed of one single fatty acid in combination with gene expression profiling to examine the acute effects of individual dietary fatty acids on hepatic gene expression in mice. The dietary interventions were performed in parallel in wild-type and PPAR-/- mice, enabling the determination of the specific contribution of PPAR. Depending on chain length and degree of saturation, dietary fatty acids caused a statistically significant change in expression of over 400 genes. Surprisingly, the far majority of genes regulated by dietary fatty acids in wild-type mice were unaltered in mice lacking PPAR, indicating PPAR-dependent regulation. We conclude that the effects of dietary fatty acids on hepatic gene expression are almost entirely mediated by PPAR, indicating that PPAR dominates fatty acid-dependent gene regulation in liver.
Publication Title
Effect of synthetic dietary triglycerides: a novel research paradigm for nutrigenomics.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) but not PPARalpha serves as a plasma free fatty acid sensor in liver.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
The present study was designed to test the hypothesis that limited growth of the fetal liver in the model of maternal fasting is independent of well-characterized signaling mechanisms that are known to regulate somatic growth in adult animals.
Publication Title
Regulation of fetal liver growth in a model of diet restriction in the pregnant rat.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus, Homo sapiens, Rattus norvegicus
- 46 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Expression 430A Array (moe430a)
Description
PPARalpha is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARalpha in hepatic lipid metabolism, many PPARalpha-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPARalpha-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPARalpha target genes, livers from several animal studies in which PPARalpha was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPARalpha-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPARalpha-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip), electron-transferring-flavoprotein beta polypeptide (Etfb), electron-transferring-flavoprotein dehydrogenase (Etfdh), phosphatidylcholine transfer protein (Pctp), endothelial lipase (EL, Lipg), adipose triglyceride lipase (Pnpla2), hormone-sensitive lipase (HSL, Lipe), and monoglyceride lipase (Mgll). Using an in silico screening approach, one or more PPAR response elements (PPREs) were identified in each of these genes. Regulation of Pnpla2, Lipe, and Mgll, which are involved in triglyceride hydrolysis, was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPARalpha agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPARalpha. Our study illustrates the power of transcriptional profiling to uncover novel PPARalpha-regulated genes and pathways in liver.
Publication Title
Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Expression 430A Array (moe430a)
Description
PPAR is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPAR in hepatic lipid metabolism, many PPAR-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPAR-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPAR target genes, livers from several animal studies in which PPAR was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPAR-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPAR-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip), electron-transferring-flavoprotein polypeptide (Etfb), electron-transferring-flavoprotein dehydrogenase (Etfdh), phosphatidylcholine transfer protein (Pctp), endothelial lipase (EL, Lipg), adipose triglyceride lipase (Pnpla2), hormone-sensitive lipase (Lipe), and monoglyceride lipase (Mgll). Using an in silico screening approach, one or more PPAR response elements (PPREs) were identified in each of these genes. Since Pnpla2, Lipe, and Mgll contribute to hepatic triglyceride hydrolysis, gene regulation was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPAR agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPAR. Our study illustrates the power of transcriptional profiling to uncover novel PPAR-regulated genes and pathways in liver.
Publication Title
Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
PPAR is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPAR in hepatic lipid metabolism, many PPAR-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPAR-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPAR target genes, livers from several animal studies in which PPAR was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPAR-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPAR-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip), electron-transferring-flavoprotein polypeptide (Etfb), electron-transferring-flavoprotein dehydrogenase (Etfdh), phosphatidylcholine transfer protein (Pctp), endothelial lipase (EL, Lipg), adipose triglyceride lipase (Pnpla2), hormone-sensitive lipase (Lipe), and monoglyceride lipase (Mgll). Using an in silico screening approach, one or more PPAR response elements (PPREs) were identified in each of these genes. Since Pnpla2, Lipe, and Mgll contribute to hepatic triglyceride hydrolysis, gene regulation was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPAR agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPAR. Our study illustrates the power of transcriptional profiling to uncover novel PPAR-regulated genes and pathways in liver.
Publication Title
Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Approximately 60-70% of patients with pulmonary sarcoidosis have a good outcome, with disease that resolves spontaneously. It is unclear why some patients progress to fibrotic disease, and there is currently no marker that differentiates these patients from those with self-limiting lung disease.
Publication Title
Gene set analysis of lung samples provides insight into pathogenesis of progressive, fibrotic pulmonary sarcoidosis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus, Homo sapiens, Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
PPAR is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPAR in hepatic lipid metabolism, many PPAR-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPAR-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPAR target genes, livers from several animal studies in which PPAR was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPAR-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPAR-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip), electron-transferring-flavoprotein polypeptide (Etfb), electron-transferring-flavoprotein dehydrogenase (Etfdh), phosphatidylcholine transfer protein (Pctp), endothelial lipase (EL, Lipg), adipose triglyceride lipase (Pnpla2), hormone-sensitive lipase (Lipe), and monoglyceride lipase (Mgll). Using an in silico screening approach, one or more PPAR response elements (PPREs) were identified in each of these genes. Since Pnpla2, Lipe, and Mgll contribute to hepatic triglyceride hydrolysis, gene regulation was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPAR agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPAR. Our study illustrates the power of transcriptional profiling to uncover novel PPAR-regulated genes and pathways in liver.
Publication Title
Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
PPAR is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPAR in hepatic lipid metabolism, many PPAR-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPAR-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPAR target genes, livers from several animal studies in which PPAR was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPAR-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPAR-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip), electron-transferring-flavoprotein polypeptide (Etfb), electron-transferring-flavoprotein dehydrogenase (Etfdh), phosphatidylcholine transfer protein (Pctp), endothelial lipase (EL, Lipg), adipose triglyceride lipase (Pnpla2), hormone-sensitive lipase (Lipe), and monoglyceride lipase (Mgll). Using an in silico screening approach, one or more PPAR response elements (PPREs) were identified in each of these genes. Since Pnpla2, Lipe, and Mgll contribute to hepatic triglyceride hydrolysis, gene regulation was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPAR agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPAR. Our study illustrates the power of transcriptional profiling to uncover novel PPAR-regulated genes and pathways in liver.
Publication Title
Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling.
Sample Metadata Fields
Sex, Specimen part
View Samples