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GRK 1482 Jahrbuch 2011-2014

Abstract BE and EAC appear to be occurring in parallel to the rapidly increasing obesity epidemic that is currently burdening the western world at a rate of 4-10% annually in western countries [3]. Using a novel mouse model of IL-1Beta overexpres-sion which subsequently develops BE and EAC, we will metabolically phenotype and asses the effects of high fat feeding in relation to the development of obesity. In parallel, we will also assess the microbiome of this novel mouse model, with the goal of further understanding the mechanisms linking obesity with EAC. Introduction The increasing incidence of gastroesophageal re- flux diseases (GERD) such as Barrett Esophagus (BE) and Esophageal Adenocarcinoma (EAC) ap- pears to be occurring in parallel to the obesity epi- demic that is currently burdening the western world. It has been well established that being overweight or obese is a precursor for type II diabetes mellitus, hypertension, glucose intolerance, cardiovascular disease (CVD), and several forms of cancer. A high body mass index (BMI) is associated with GERD and frequent reflux strongly correlates with EAC. Mechanisms by which obesity may be responsib- le for GERD related disorders include the mecha- nical pathogenesis caused by increase abdominal obesity resulting in an increase in intragastric pres- sure, and the hypothesis that the hormonal, endo- crine and paracrine activity of the adipose tissue itself might lead to contribute to the pathogenesis of GERD. The main risk factor for EAC is BE, which is strongly associated with GERD. BE is a premali- gnant [1] condition of the distal esophagus where the normal squamous epithelium in the esopha- gus is replaced by columnar epithelium, typically with intestinal metaplasia [2]. BE is the initial step in the histopathological progression that can lead to low-grade dysplasia, high-grade dysplasia and ultimately esophageal adenocarcinoma. Our observations and studies are based on a novel mouse model of IL-1Beta overexpression. This mouse model subsequently develops BE and EAC over time. Our intention is to study the effects of high fat feeding (HFF) on the development of BE and EAC in this model in order to better understand the underlying mechanisms that link obesity with EAC. Based on preliminary observations of the mo- del at Columbia University, New York, we had origi- nally hypothesized, that HFF would accelerate the onset of obesity, thereby accelerating the develop- ment of BE and EAC. The most recent observations on the model, housed in Freising, shows that high fat feeding does infact accelerate the development of BE and EAC, however there does not appear to be a dramatic increase in weight gain as expected. PhD FELLOWS Page 48 | GRK Progress Report 2011-2014 Natasha Stephens (M.Sc.) Klinikum rechts der Isar | Internal Medicine II PhD 9/2 Role and function of IL-1β and IL-6 in a distinct mouse model of gut epithelial IL-1β over-expression