title: Maternal obesity induces sustained inflammation in both fetal and offspring large intestine of sheep.
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.
authors.affiliation: Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, Wyoming, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Yan
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Du
authors.forename: Bret W
authors.initials: BW
authors.lastname: Hess
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Ford
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nathanielsz
authors.forename: Mei-Jun
authors.initials: MJ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D015153:Blotting, Western; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000276:immunology / Q000473:pathology*; D005355:Fibrosis / Q000209:etiology* / Q000473:pathology; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D007420:Intestine, Large / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D039382:Maternal Nutritional Physiological Phenomena; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000150:complications*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D016328:NF-kappa B; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta