Lay Summary

Proposal No. IBD-0286
Principal Investigator: Iordanis Karagiannidis, Ph.D. 
Applicant Organization: University of California, Los Angeles (U.S.A.)
Project Title: Effects of obesity in colitis-associated changes in the intestine and mesenteric adipose tissue 
Period of Award:  November 1, 2009 – February 29, 2012

During Crohn’s disease, a mass of abdominal fat tissue, termed “creeping” fat, expands and envelops the inflamed area of the patient’s colon. The size of this fat mass is often used by surgeons to describe the extent of inflammation and damage in the colon. However, the role of this fat depot in the overall course of the disease has not been evaluated. The emergence of data that portray fat depots as immune organs and link obesity with increased inflammatory infiltrate within fat tissue, leads to the speculation that, changes in the physiological condition of fat during obesity as well as fat expansion and wrapping of the bowel in Crohn’s, may represent contributing factors to the development and progression of inflammatory bowel disease (IBD). Despite the increasing evidence implicating fat (and especially obesity) as a significant contributor in the development of several serious diseases, its potential contribution to the development of IBD has not been studied. In this proposal we will investigate whether pre-existing obesity affects the development of IBD through its effects on the inflammatory status of fat depots that are located close to the colon within the abdominal cavity. For this we will use a mouse model that combines obesity and intestinal inflammation that resembles the Crohn’s disease pathological outcome. We will collect information that describes the state of inflammation of abdominal fat depots of obese versus non-obese mice and these differences translate in the extent of intestinal inflammation. In addition, we will use human fat cells that are isolated from IBD patient’s fat tissue that is close or far from the inflamed colon, and also will compare their inflammatory state to cells from non-IBD patient fat depots. The information will provide insight on the effects of obesity on the outcome of intestinal inflammation as well as a comparison between fat cells residing in expanding fat masses during obesity and Crohn’s disease. Investigating the involvement of fat tissue in the pathogenesis of IBD adds a different dimension in the effort to understand its pathophysiology and may lead to the development of prevention strategies and more efficient clinical approaches.