Accepted manuscript
Maternal Obesity Induces Sustained Inflammation in Both Fetal and Offspring Large Intestine of Sheep
Inflammatory bowel diseases, Vol.17(7), pp.1513-1522
07/2011
Handle:
https://hdl.handle.net/2376/106073
PMCID: PMC3116110
PMID: 21674707
Abstract
Background: Both maternal obesity and inflammatory bowel diseases (IBDs) are increasing. It was hypothesized that maternal obesity induces an inflammatory response in the fetal large intestine, predisposing offspring to IBDs.
Methods: Nonpregnant ewes were assigned to a control (Con, 100% of National Research Council [NRC] recommendations) or obesogenic (OB, 150% of NRC) diet from 60 days before conception. The large intestine was sampled from fetuses at 135 clays (term 150 clays) after conception and from offspring lambs at 22.5 +/- 0.5 months of age.
Results: Maternal obesity enhanced mRNA expression tumor necrosis factor (TNF)alpha, interleukin (IL)1 alpha, IL1 beta, IL6, IL8, and monocyte/macrophage chemotactic protein-1 (MCP1), as well as macrophage markers, CD11b, CD14, and CD68 in fetal gut. mRNA expression of Toll-like receptor (TLR) 2 and TLR4 was increased in OB versus Con fetuses; correspondingly, inflammatory NF-kappa B and JNK signaling pathways were also upregulated. Both mRNA expression and protein content of transforming growth factor (TGF) beta was increased. The IL-17A mRNA expression and protein content was higher in OB compared to Con samples, which was associated with fibrosis in the large intestine of OB fetuses. Similar inflammatory responses and enhanced fibrosis were detected in OB compared to Con offspring.
Conclusions: Maternal obesity induced inflammation and enhanced expression of proinflammatory cytokines in fetal and offspring large intestine, which correlated with increased TGF beta and IL 17 expression. These data show that maternal obesity may predispose offspring gut to IBDs.
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Details
- Title
- Maternal Obesity Induces Sustained Inflammation in Both Fetal and Offspring Large Intestine of Sheep
- Creators
- Xu Yan - Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WyomingYan Huang - Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WyomingHui Wang - Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WyomingMin Du - Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WyomingBret W Hess - Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WyomingStephen P Ford - Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WyomingPeter W Nathanielsz - Center for Pregnancy and Newborn Research, University of Texas Health Sciences Center, San Antonio, TexasMei-Jun Zhu - Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, Wyoming
- Publication Details
- Inflammatory bowel diseases, Vol.17(7), pp.1513-1522
- Academic Unit
- Department of Animal Sciences
- Publisher
- Oxford Univ Press
- Number of pages
- 10
- Grant note
- P20RR016474 / NIH INBRE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 2008-35203-19084 / USDA-NRI; United States Department of Agriculture (USDA)
- Identifiers
- 99900546822901842
- Language
- English
- Resource Type
- Accepted manuscript