Duodenal Peyer's Patch Gene Expression Altered Following Rodent Vertical Sleeve Gastrectomy

Abstract

Bariatric surgery as a method of long term surgical associated weight loss continues to grow in popularity due to the positive metabolic health benefits reported; however, the mechanisms that produce surgical weight loss are not yet fully understood. In previous studies using our rodent model of vertical sleeve gastrectomy (VSG), it was reported that VSG results in uninhibited gastric emptying resulting in remodeling of the duodenum and various other structural changes within the intestine. We anticipate that the remodeling of the intestine would drive changes in the immune milieu of the gut. The objective of this study is to investigate the effect VSG has on the gene expression of the Peyer's patches, a component of gut‐associated lymphoid tissue that lie beneath the mucosal layer and monitor intestinal bacteria population to prevent the growth of pathogenic bacteria in the intestines. We evaluated male Long Evans rats (N=13) having received Sham‐Surgery or VSG and fed a standard chow diet post‐operatively. VSG animals lost significant amounts of body mass and fat mass and ate less in comparison to sham males during the first 5 post‐operative weeks. During post‐operative week 16, animals were euthanized and intestinal Peyer's patches were harvested for gene expression studies. RNAseq coupled with further data analysis using Illumina Software coupled with Ingenuity Pathway Analysis Software (IPA) was performed on duodenal Peyer's patches from Sham and VSG. The top Canonical Pathways having differentially‐expressed genes include LPS/IL‐1 Family, FXR Activation and Fatty Acid Activation Canonical Pathways. After determining relevant genes of interest, rtPCR was performed to validate the RNAseq data. We reported a significant decrease in tight junction‐associated claudin (CLDN8, P < 0.05) as well as increases in the facilitated glucose transporter (SLC2A4, P < 0.05), fatty acid signaling molecule (APOE, P < 0.05), and macrophage marker (CD68, P < 0.05). We have further preliminary evidence that there is elevated lipopolysaccharide binding protein (LBP) in circulation of VSG in comparison to Sham. Taken together, these data suggested a reduced intestinal barrier that leads to compromised intestinal integrity and reorganized PP architecture.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.