Comparative analysis of gene regulation by the transcription factor PPARα_mouse

Dataset

Description

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.
Date made available21 Sep 2009
PublisherWageningen University

Research Output

Plasma mannose-binding lectin is stimulated by PPARa in humans

Rakhshandehroo, M., Stienstra, R., de Wit, N. J. W., Bragt, M. C. E., Haluzik, M., Mensink, R. P., Muller, M. R. & Kersten, A. H., 2012, In : American Journal of Physiology. Endocrinology and Metabolism. 302, 5, p. E595-E602 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • 15 Citations (Scopus)

    Comparative Analysis of Gene Regulation by the Transcription Factor PPARa between Mouse and Human

    Rakhshandehroo, M., Hooiveld, G. J. E. J., Müller, M. R. & Kersten, A. H., 2009, In : PLoS ONE. 4, 8, 13 p., e6796.

    Research output: Contribution to journalArticleAcademicpeer-review

    Open Access
  • 176 Citations (Scopus)

    Datasets

    Comparative analysis of gene regulation by the transcription factor PPARα_human

    Rakhshandehroo, M. (Creator), Hooiveld, G. (Creator), Muller, M. (Creator) & Kersten, S. (Creator), Wageningen University, 21 Sep 2009

    Dataset

    Cite this

    Rakhshandehroo, M. (Creator), Hooiveld, G. (Creator), Muller, M. (Creator), Kersten, S. (Creator) (21 Sep 2009). Comparative analysis of gene regulation by the transcription factor PPARα_mouse. Wageningen University.