G.H. Gershner1,2, K.B. Snyder1,2, C.M. Dalton1,2, H.C. Grubbs1,2, D.N. Reuter3, J.F. Papin4, S. Gurung5, K.R. Jonscher6, D.A. Myers5, C.J. Hunter1,2 1University Of Oklahoma College Of Medicine, Pediatric Surgery, Oklahoma City, OK, USA 2University Of Oklahoma College Of Medicine, Surgery, Oklahoma City, OK, USA 3University Of Oklahoma College Of Medicine, Comparative Medicine, Oklahoma City, OK, USA 4University Of Oklahoma College Of Medicine, Pathology, Oklahoma City, OK, USA 5University Of Oklahoma College Of Medicine, Obstetrics And Gynecology, Oklahoma City, OK, USA 6University Of Oklahoma College Of Medicine, Biochemistry And Physiology, Oklahoma City, OK, USA
Introduction: Obesity and consumption of a “Western” diet (WD) have been linked to pathologies including cancers and metabolic diseases. This is partly due to a chronic inflammatory response associated with excess adiposity and weight gain, insulin spikes, and excess cholesterol exposure. The effects of this hyperinflammatory state are currently understudied in fetuses. Using a novel nonhuman primate model of maternal obesity, we hypothesize that WD exposure in baboon dams will lead to a hyperinflammatory state, resulting in decreased intestinal barrier function in fetuses.
Methods: Intestinal tissue was harvested from twenty Papio anubis baboon fetuses. RNA was extracted from the tissue and qPCR used to measure relative gene expression. Enteroids were also generated, plated onto a TransWellTM plate and Transepithelial electrical resistance (TEER) measurements were taken. The maximum TEER measured in each well represented maximal barrier function. TEER measurements and gene expression were compared between maternal control diet (CD) and WD groups.
Results: We found elevations in mRNA expression levels of IL-1β, IL-8, IL-10, IFNγ, TNFα, and TLR4. While there was a positive trend, most were not significantly elevated (IL-1β p=0.4496, IL-8 p=0.4290, IL-10 p=0.0878, TNFα p=0.4201, TLR4 p=0.1449). IL-6 and IFNγ were significantly elevated (p<0.0001 and p=0.0021respectively). There was a significant reduction in the maximum TEER achieved in the WD (353.45 ± 122.93) compared to the CD (575.1 ± 108.19; p=0.0117).
Conclusion: Exposure to maternal WD resulted in significantly increased expression of IL-6 and IFNγ, as well as other markers of intestinal inflammation. The inflammatory state was associated with a statistically significant decrease in WD barrier function when compared to CD counterparts. The combination of a hyperinflammatory state and decreased barrier function may increase neonatal risk for conditions like necrotizing enterocolitis.