comparative analysis of gene regulation by the transcription factor pparα between mouse and human比较分析基因调控的转录因子pparα老鼠和人类之间.pdfVIP

Comparative Analysis of Gene Regulation by the Transcription Factor PPARa between Mouse and Human 1,2 1,2 ¨ 1,2 1,2 Maryam Rakhshandehroo , Guido Hooiveld , Michael Muller , Sander Kersten * 1 Nutrigenomics Consortium, Top Institute (TI) Food and Nutrition, Wageningen, the Netherlands, 2 Nutrition, Metabolism and Genomics group, Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands Abstract Background: Studies in mice have shown that PPARa is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPARa in human liver. Here we set out to compare the function of PPARa in mouse and human hepatocytes via analysis of target gene regulation. Methodology/Principal Findings: Primary hepatocytes from 6 human and 6 mouse donors were treated with PPARa agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPARa 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 PPARa in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were invo