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Bünger, Meike, van den Bosch, Heleen M, van der Meijde, Jolanda, Kersten, Sander, Hooiveld, Guido J E J and Müller, Michael 
ORCID: https://orcid.org/0000-0002-5930-9905
(2007)
Genome-wide analysis of PPARalpha activation in murine small intestine.
Physiological Genomics, 30 (2).
pp. 192-204.
ISSN 1094-8341
Abstract
The peroxisome proliferator-activated receptor alpha (PPARalpha) is a fatty acid-activated transcription factor that governs a variety of biological processes. Little is known about the role of PPARalpha in the small intestine. Since this organ is frequently exposed to high levels of PPARalpha ligands via the diet, we set out to characterize the function of PPARalpha in small intestine using functional genomics experiments and bioinformatics tools. PPARalpha was expressed at high levels in both human and murine small intestine. Detailed analyses showed that PPARalpha 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 PPARalpha activation. Additional analyses showed that intestinal PPARalpha-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 PPARalpha in the small intestine. We show that PPARalpha 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | animals,fenofibrate,gene expression profiling,genome,humans,intestine, small,mice,mice, knockout,nucleic acid hybridization,oligonucleotide array sequence analysis,ppar alpha,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Depositing User: | Pure Connector |
| Date Deposited: | 07 Jul 2014 12:02 |
| Last Modified: | 06 Jun 2024 14:47 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/47722 |
| DOI: | 10.1152/physiolgenomics.00198.2006 |
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