Maternal obesity induces sustained inflammation in both fetal and offspring large intestine of sheep

Xu Yan, Yan Huang, Hui Wang, Min Du, Bret W. Hess, Stephen P. Ford, Peter W. Nathanielsz, Mei Jun Zhu

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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 days (term 150 days) after conception and from offspring lambs at 22.5 ± 0.5 months of age. Results: Maternal obesity enhanced mRNA expression tumor necrosis factor (TNF)α, interleukin (IL)1α, IL1β, 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-κB and JNK signaling pathways were also upregulated. Both mRNA expression and protein content of transforming growth factor (TGF) β 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 TGFβ and IL17 expression. These data show that maternal obesity may predispose offspring gut to IBDs.

Original languageEnglish (US)
Pages (from-to)1513-1522
Number of pages10
JournalInflammatory Bowel Diseases
Volume17
Issue number7
DOIs
StatePublished - Jul 2011

Keywords

  • fetus
  • gut
  • inflammation
  • inflammatory bowel disease
  • obesity
  • offspring
  • sheep

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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