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Metabolic Phenotyping of the Crohn's Disease-like IBD Etiopathology in the TNFΔARE/WT Mouse Model

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Chair for Biofunctionality, ZIEL−Research Center for Nutrition and Food Science, CDD - Center for Diet and Disease, Technische Universität München, Gregor-Mendel-Strasse 2, 85350 Freising-Weihenstephan, Germany
Nestlé Research Center, P.O. Box 44, Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland
§ Chair for Molecular Nutritional Medicine, Else-Kröner Fresenius Center, Technische Universität München, Gregor-Mendel-Strasse 2, 85350 Freising-Weihenstephan, Germany
Institute of Immunology, Alexander Fleming Biomedical Sciences Research Center, 34 Al. Fleming Street, Vari, Greece
Dirk Haller, Ph.D., Professor, Biofunctionality, Technische Universität München, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany. E-mail: [email protected]. Phone +49-8161-71-2026. Fax +49-8161-71-2824*Francois-Pierre Martin, Ph.D., Nestlé Research Center, BioAnalytical Sciences, P. O. Box 44, Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland. Email: [email protected]. Phone +41-21-785-8771.
Cite this: J. Proteome Res. 2011, 10, 12, 5523–5535
Publication Date (Web):October 26, 2011
Copyright © 2011 American Chemical Society

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    The underlying biochemical consequences of inflammatory bowel disease (IBD) on the systemic and gastrointestinal metabolism have not yet been fully elucidated but could help to better understand the disease pathogenesis and to identify tissue-specific markers associated with the different disease stages. Here, we applied a metabonomic approach to monitor metabolic events associated with the gradual development of Crohn's disease (CD)-like ileitis in the TNFΔARE/WT mouse model. Metabolic profiles of different intestinal compartments from the age of 4 up to 24 weeks were generated by combining proton nuclear magnetic resonance (1H NMR) spectroscopy and liquid chromatography–mass spectrometry (LC–MS). From 8 weeks onward, mice developed CD similar to the immune and tissue-related phenotype of human CD with ileal involvement, including ileal histological abnormalities, reduced fat mass and body weight, as well as hallmarks of malabsorption with higher energy wasting. The metabonomic approach highlighted shifts in the intestinal lipid metabolism concomitant to the histological onset of inflammation. Moreover, the advanced disease status was characterized by a significantly altered metabolism of cholesterol, triglycerides, phospholipids, plasmalogens, and sphingomyelins in the inflamed tissue (ileum) and the adjacent intestinal parts (proximal colon). These results describe different biological processes associated with the disease onset, including modifications of the general cell membrane composition, alteration of energy homeostasis, and finally the generation of inflammatory lipid mediators. Taken together, this provides novel insights into IBD-related alterations of specific lipid-dependant processes during inflammatory states.

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