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Series GSE5475 Query DataSets for GSE5475
Status Public on Jun 28, 2007
Title Genome-wide analysis of PPARα activation in murine small intestine
Organism Mus musculus
Experiment type Expression profiling by array
Summary The peroxisome proliferator-activated receptor alpha (PPARα) is a fatty acid-activated transcription factor that governs a variety of biological processes. Little is known about the role of PPARα in the small intestine. Since this organ is frequently exposed to high levels of PPARα ligands via the diet, we set out to characterize the function of PPARα in small intestine using functional genomics experiments and bioinformatics tools. PPARα was expressed at high levels in both human and murine small intestine. Detailed analyses showed that PPARα was expressed highest in villus cells of proximal jejunum. Microarray analyses of total tissue samples revealed, that in addition to genes involved in fatty acid and triacylglycerol metabolism, transcription factors and enzymes connected to sterol and bile acid metabolism, including FXR and SREBP1, were specifically induced. In contrast, genes involved in cell cycle and differentiation, apoptosis, and host defense were repressed by PPARα activation. Additional analyses showed that intestinal PPARα dependent gene regulation occurred in villus cells. Functional implications of array results were corroborated by morphometric data. The repression of genes involved in proliferation and apoptosis was accompanied by a 22% increase in villus height, and a 34% increase in villus area of wild-type animals treated with WY14643. This is the first report providing a comprehensive overview of processes under control of PPARα in the small intestine. We show that PPARα is an important transcriptional regulator in small intestine, which may be of importance for the development of novel foods and therapies for obesity and inflammatory bowel diseases.
Keywords: identification of target genes
Overall design Pure bred wild-type (129S1/SvImJ) and PPARα-null (129S4/SvJae) mice were treated with the synthetic PPARα ligand WY14,643 (0.1% w/w) for 5 days. The complete intestines were then removed and total RNA was isolated.
In total 4 experimental groups were present: wild type mice fed the control diet (AIN93M), wild type mice fed the control diet supplemented with 0.1% w/w WY14,643 for 5 days, PPARα knockout mice fed the control diet, PPARα knockout mice fed the control diet supplemented with 0.1% w/wWY14,643 for 5 days.
RNA of 3 biological replicates was hybridized to Affymetrix 430A arrays.
Five microgram total RNA was labelled according to the ENZO-protocol, fragmented and hybridized according to Affymetrix's protocols.
Contributor(s) Bunger M, van den Bosch HM, van der Meijde J, Kersten S, Hooiveld GJ, Muller M
Citation(s) 17426115
Submission date Aug 08, 2006
Last update date Jan 08, 2019
Contact name Guido Hooiveld
Organization name Wageningen University
Department Div. Human Nutrition & Health
Lab Nutrition, Metabolism & Genomics Group
Street address HELIX, Stippeneng 4
City Wageningen
ZIP/Postal code NL-6708WE
Country Netherlands
Platforms (1)
GPL339 [MOE430A] Affymetrix Mouse Expression 430A Array
Samples (12)
GSM124308 intestine_wildtype_control_rep1
GSM124309 intestine_wildtype_control_rep2
GSM124310 intestine_wildtype_control_rep3
BioProject PRJNA95989

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Supplementary file Size Download File type/resource
GSE5475_RAW.tar 26.7 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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