PMID- 21674707 OWN - NLM STAT- MEDLINE DCOM- 20111028 LR - 20211020 IS - 1536-4844 (Electronic) IS - 1078-0998 (Print) IS - 1078-0998 (Linking) VI - 17 IP - 7 DP - 2011 Jul TI - Maternal obesity induces sustained inflammation in both fetal and offspring large intestine of sheep. PG - 1513-22 LID - 10.1002/ibd.21539 [doi] AB - 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)alpha, interleukin (IL)1alpha, IL1beta, 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-kappaB 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 TGFbeta and IL17 expression. These data show that maternal obesity may predispose offspring gut to IBDs. CI - Copyright (c) 2010 Crohn's & Colitis Foundation of America, Inc. FAU - Yan, Xu AU - Yan X AD - Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, Wyoming, USA. FAU - Huang, Yan AU - Huang Y FAU - Wang, Hui AU - Wang H FAU - Du, Min AU - Du M FAU - Hess, Bret W AU - Hess BW FAU - Ford, Stephen P AU - Ford SP FAU - Nathanielsz, Peter W AU - Nathanielsz PW FAU - Zhu, Mei-Jun AU - Zhu MJ LA - eng GR - P20 RR016474/RR/NCRR NIH HHS/United States GR - P20 RR016474-10/RR/NCRR NIH HHS/United States GR - P20RR016474/RR/NCRR NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. DEP - 20101128 PL - England TA - Inflamm Bowel Dis JT - Inflammatory bowel diseases JID - 9508162 RN - 0 (Cytokines) RN - 0 (Interleukin-17) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta) SB - IM MH - Animals MH - Animals, Newborn/*immunology MH - Blotting, Western MH - Cytokines/genetics/metabolism MH - Female MH - Fetus/immunology/*pathology MH - Fibrosis/*etiology/pathology MH - Inflammation/*etiology/pathology MH - Interleukin-17/genetics/metabolism MH - Intestine, Large/*immunology/metabolism/pathology MH - Maternal Nutritional Physiological Phenomena MH - NF-kappa B/genetics/metabolism MH - Obesity/*complications MH - RNA, Messenger/genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Sheep MH - Transforming Growth Factor beta/genetics/metabolism PMC - PMC3116110 MID - NIHMS240498 EDAT- 2011/06/16 06:00 MHDA- 2011/10/29 06:00 PMCR- 2012/07/01 CRDT- 2011/06/16 06:00 PHST- 2010/09/17 00:00 [received] PHST- 2010/09/23 00:00 [accepted] PHST- 2011/06/16 06:00 [entrez] PHST- 2011/06/16 06:00 [pubmed] PHST- 2011/10/29 06:00 [medline] PHST- 2012/07/01 00:00 [pmc-release] AID - 10.1002/ibd.21539 [doi] PST - ppublish SO - Inflamm Bowel Dis. 2011 Jul;17(7):1513-22. doi: 10.1002/ibd.21539. Epub 2010 Nov 28.