Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 497829
Title Maternal high-fat diet accelerates development of Crohn's disease-like ileitis in TNF ΔaRE/WT offspring
Author(s) Gruber, Lisa; Hemmerling, Jana; Schüppel, Valentina; Müller, Michael; Boekschoten, M.V.; Haller, Dirk
Source Inflammatory Bowel Diseases 21 (2015)9. - ISSN 1078-0998 - p. 2016 - 2025.
DOI https://doi.org/10.1097/MIB.0000000000000465
Department(s) Human Nutrition (HNE)
Chair Nutrition Metabolism and Genomics
VLAG
Publication type Refereed Article in a scientific journal
Publication year 2015
Keyword(s) High-fat diet - Inflammatory bowel diseases - Maternal imprinting - Obesity - Transcriptomics
Abstract

Background: Maternal high-fat diet (HFD) and obesity increases the risk of the offspring to develop inflammatory processes in various organs including the gut. We hypothesized that maternal diet-induced obesity programs the fetal gut towards inflammation in a mouse model of genetically-driven Crohn's disease (CD)-like ileitis. Methods: TNF WT/WT (WT) and TNF ΔARE/WT (ARE) dams were fed an experimental control diet (CTRLD; 13 kJ% fat) or HFD (48 kJ%). Offspring mice were fed CTRLD or HFD at 4 weeks of age. Metabolic characteristics and severity of CD-like ileitis was assessed in 8-and 12-week old WT and ARE offspring measuring tissue histopathology and markers of inflammation in the distal ileum as well as plasma cytokine and LPS levels. To study prenatal effects, we laser microdissected fetal intestinal epithelial cells at 17.5 days postconception and performed microarray-based global gene expression analysis. Results: Maternal HFD significantly accelerated the severity of CD-like ileitis in HFD-fed ARE mice at early life stages associated with increased mucosal neutrophil infiltration, Il12p40 expression, and portal vein LPS levels. In contrast to WT mice, metabolic characteristics of ARE offspring were not affected by maternal HFD. Gene expression patterns in fetal intestinal epithelial cells of ARE mice remained largely unchanged under conditions of maternal diet-induced obesity suggesting that the positive association of intestinal inflammation, portal vein endotoxemia, and plasma TNF levels is independent of prenatal conditioning of the gut epithelium. Conclusions: Maternal HFD promotes the early onset of severe CD-like ileitis in genetically susceptible offspring independent of metabolic alterations.

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