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Series GSE17254 Query DataSets for GSE17254
Status Public on Sep 04, 2009
Title Comparative analysis of gene regulation by the transcription factor PPARα between mouse and human
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by array
Summary Studies in mice have shown that PPARα is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPARα in human liver. Here we set out to compare the function of PPARα in mouse and human hepatocytes via analysis of target gene regulation. Primary hepatocytes from 6 human and 6 mouse donors were treated with PPARα agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPARα expression was similar in human and mouse hepatocytes. Depending on species and time of exposure, Wy14643 significantly induced the expression of 362-672 genes. Surprisingly minor overlap was observed between the Wy14643-regulated genes from mouse and human, although more substantial overlap was observed at the pathway level. Xenobiotics metabolism and apolipoprotein synthesis were specifically regulated by PPARα in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPARα targets, including CPT1A, HMGCS2, FABP, ACSL, and ADFP. Several genes were identified that were specifically induced by PPARα in human (MBL2, ALAS1, CYP1A1, TSKU) or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4). Furthermore, several putative novel PPARα targets were identified that were commonly regulated in both species, including CREB3L3, KLF10, KLF11 and MAP3K8. Our results suggest that PPARα activation has a major impact on gene regulation in human hepatocytes. Importantly, the role of PPARα as master regulator of hepatic lipid metabolism is generally well-conserved between mouse and human. Overall, however, PPARα regulates a mostly divergent set of genes in mouse and human hepatocytes.

This SuperSeries is composed of the SubSeries listed below.
 
Overall design Refer to individual Series
 
Contributor(s) Rakhshandehroo M, Hooiveld G, Müller M, Kersten S
Citation(s) 19710929, 22215653
Submission date Jul 22, 2009
Last update date Feb 11, 2019
Contact name Guido Hooiveld
E-mail guido.hooiveld@wur.nl
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 (2)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (48)
GSM432115 NMRI_6h_Wy
GSM432116 NMRI_6h_DMSO
GSM432117 NMRI_24h_Wy
This SuperSeries is composed of the following SubSeries:
GSE17250 Comparative analysis of gene regulation by the transcription factor PPARα_mouse
GSE17251 Comparative analysis of gene regulation by the transcription factor PPARα_human
Relations
BioProject PRJNA118935

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE17254_RAW.tar 194.7 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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