About this Journal Submit a Manuscript Table of Contents
PPAR Research
Volume 2007 (2007), Article ID 26839, 13 pages
http://dx.doi.org/10.1155/2007/26839
Research Article

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

1Nutrigenomics Consortium, Wageningen Centre for Food Sciences, P.O. BOX 557, Wageningen 6700 AN, The Netherlands
2Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, P.O. BOX 8129, Wageningen 6700 EV, The Netherlands
3Life Sciences Research Unit, University of Luxembourg, 162A Avenue de la Faïencerie, Luxembourg 1511, Luxembourg

Received 17 May 2007; Accepted 25 July 2007

Academic Editor: Michael L. Cunningham

Copyright © 2007 Maryam Rakhshandehroo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

PPARα is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARα in hepatic lipid metabolism, many PPARα-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPARα-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPARα target genes, livers from several animal studies in which PPARα was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPARα-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPARα-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip), electron-transferring-flavoprotein β 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 PPARα 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 PPARα. Our study illustrates the power of transcriptional profiling to uncover novel PPARα-regulated genes and pathways in liver.