Scientific Abstract
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
Recent clinical studies have demonstrated that obesity is associated with the development of active inflammatory bowel disease (IBD) and requirement for hospitalization, and significantly decreased the time span between diagnosis and surgery. In addition, studies with animal models of colitis showed obesity-dependent effects on the T-cell populations involved in the development of intestinal inflammation. If changes in the inflammatory milieu of mesenteric fat depots can influence intestinal responses, increases in adiposity are also likely to influence the progression of inflammatory changes in IBD. Our study aims to investigate the importance of adipose tissue in the development of inflammatory responses within the intestine.
We will use a mouse model that combines increased adiposity with chronic (TNBS, Crohn’s-reminiscent) or spontaneous (genetic, IL-10-/- model) colitis. For this we will feed C57BL/6 mice with a high fat content diet that causes obesity and then we will use weekly intracolonic injections of TNBS to induce colitis. For the IL-10-/- mice, the rate of spontaneous colitis development will be observed between obese and control mice. Mesenteric fat depots as well as intestinal tissue will then be used for analysis of inflammatory responses both at the molecular and the histological levels. Mesenteric preadipocytes and adipocytes from these tissues will also be used in cell culture to examine their proinflammatory potential on RAW.1 macrophages. Similar analyses will also be performed on human mesenteric preadipocytes derived from mesenteric “creeping” fat of Crohn’s disease patients.
Such data may identify novel cellular and whole tissue targets for investigation on the causes of IBD and expose obesity as a risk factor for exacerbation of the outcome of such diseases.