Comprehensive analysis of PPARa-dependent regulation of hepatic lipid metabolism by expression profiling

  • Maryam Rakhshandehroo (Creator)
  • L.M. Sanderson-Kjellberg (Creator)
  • Merja Matilainen (Creator)
  • Rinke Stienstra (Creator)
  • Carsten Carlberg (Creator)
  • Philip de Groot (Creator)
  • Michael Muller (Creator)
  • Sander Kersten (Creator)

Dataset

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.
Date made available24 Jul 2007
PublisherWageningen University

Research Output

Comprehensive Analysis of PPARa-Dependent Regulation of Hepatic Lipid Metabolism by Expression Profiling

Rakhshandehroo, M., Sanderson-Kjellberg, L. M., Matilainen, M., Stienstra, R., Carlberg, C., de Groot, P. J., Müller, M. R. & Kersten, A. H., 2007, In : PPAR Research. 2007, 13 p., 26839.

Research output: Contribution to journalArticleAcademicpeer-review

Open Access
  • 147 Citations (Scopus)

    Datasets

    Comprehensive analysis of PPARα-dependent regulation of hepatic lipid metabolism by expression profiling - 5

    Rakhshandehroo, M. (Creator), Sanderson-Kjellberg, L. M. (Creator), Matilainen, M. (Creator), Stienstra, R. (Creator), Carlberg, C. (Creator), de Groot, P. (Creator), Muller, M. (Creator) & Kersten, S. (Creator), Wageningen University, 24 Jul 2007

    Dataset

    Comprehensive analysis of PPARα-dependent regulation of hepatic lipid metabolism by expression profiling - 2

    Rakhshandehroo, M. (Creator), Sanderson-Kjellberg, L. M. (Creator), Matilainen, M. (Creator), Stienstra, R. (Creator), Carlberg, C. (Creator), de Groot, P. (Creator), Muller, M. (Creator) & Kersten, S. (Creator), Wageningen University, 24 Jul 2007

    Dataset

    Comprehensive analysis of PPARα-dependent regulation of hepatic lipid metabolism by expression profiling - 4

    Rakhshandehroo, M. (Creator), Sanderson-Kjellberg, L. M. (Creator), Matilainen, M. (Creator), Stienstra, R. (Creator), Carlberg, C. (Creator), de Groot, P. (Creator), Muller, M. (Creator) & Kersten, S. (Creator), Wageningen University, 24 Jul 2007

    Dataset

    Cite this

    Rakhshandehroo, M. (Creator), Sanderson-Kjellberg, L. M. (Creator), Matilainen, M. (Creator), Stienstra, R. (Creator), Carlberg, C. (Creator), de Groot, P. (Creator), Muller, M. (Creator), Kersten, S. (Creator) (24 Jul 2007). Comprehensive analysis of PPARa-dependent regulation of hepatic lipid metabolism by expression profiling. Wageningen University.