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Physiol. Genomics 30: 192-204, 2007. First published April 10, 2007; doi:10.1152/physiolgenomics.00198.2006
1094-8341/07 $8.00
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Received 11 September 2006; accepted in final form 3 April 2007.
Physiological Genomics 30:192-204 (2007)
1094-8341/07 $8.00 © 2007 American Physiological Society

Genome-wide analysis of PPAR{alpha} activation in murine small intestine

Meike Bünger1,2, Heleen M. van den Bosch1,2, Jolanda van der Meijde1, Sander Kersten1,2, Guido J. E. J. Hooiveld1,2 and Michael Müller1,2

1 Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University
2 Nutrigenomics Consortium, Wageningen Centre for Food Sciences, Wageningen, the Netherlands

The peroxisome proliferator-activated receptor alpha (PPAR{alpha}) is a fatty acid-activated transcription factor that governs a variety of biological processes. Little is known about the role of PPAR{alpha} in the small intestine. Since this organ is frequently exposed to high levels of PPAR{alpha} ligands via the diet, we set out to characterize the function of PPAR{alpha} in small intestine using functional genomics experiments and bioinformatics tools. PPAR{alpha} was expressed at high levels in both human and murine small intestine. Detailed analyses showed that PPAR{alpha} was expressed most highly in villus cells of proximal jejunum. Microarray analyses of total tissue samples revealed, that in addition to genes involved in fatty acid and triacylglycerol metabolism, transcription factors and enzymes connected to sterol and bile acid metabolism, including FXR and SREBP1, were specifically induced. In contrast, genes involved in cell cycle and differentiation, apoptosis, and host defense were repressed by PPAR{alpha} activation. Additional analyses showed that intestinal PPAR{alpha}-dependent gene regulation occurred in villus cells. Functional implications of array results were corroborated by morphometric data. The repression of genes involved in proliferation and apoptosis was accompanied by a 22% increase in villus height and a 34% increase in villus area of wild-type animals treated with WY14643. This is the first report providing a comprehensive overview of processes under control of PPAR{alpha} in the small intestine. We show that PPAR{alpha} is an important transcriptional regulator in small intestine, which may be of importance for the development of novel foods and therapies for obesity and inflammatory bowel diseases.

microarray; peroxisome proliferator-activated receptor alpha; gene expression; crypt-villus axis; lipid absorption; proximal-distal axis




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