9th Annual BMRP Investigator Meeting - Abstract
Effects of Diet Induced Obesity in the Outcome of Experimental Colitis (TNBS) in C57BL/6 Mice
Iordanis Karagiannidisa, Dimitris Stavrakis, Collin Bowe, Hon-Wai Koon and Charalabos Pothoulakis
Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles (Los Angeles, California, U.S.A.)
Obesity has long been considered a “low grade inflammatory state” and a major contributor in the development of several diseases with an inflammatory component. Several studies demonstrated that adipose tissue is the source of a number of hormones and proinflammatory factors. Recent clinical studies have demonstrated that obesity in associated with the development of active disease 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. Our goal in this study is to investigate whether high fat diet-induced obesity alters the course of chemically-induced intestinal inflammation and evaluate the extent of mesenteric fat depot involvement. Male C57BL/6 mice were either fed high fat diet or chow and were then treated with TNBS to induce colitis or ethanol for controls. Protein and RNA were isolated from mesenteric fat depots and intestine. Light microscopic analysis showed higher levels of inflammatory cell infiltrate in the intestine and adipose tissue of obese mice when compared to all other groups. These animals also had increased histological damage in the intestine. MPO assay analysis showed increased enzyme activity in fat from TNBS treated animals under both dietary conditions but especially in the tissues isolated from high fat-fed animals. Furthermore, obesity also increased the expression of numerous proinflammatory cytokines, and reversed the TNBS-induced increases in IL-2 and IFNg (two cytokines involved in T-cell maturation processes) in both adipose and intestinal tissues. Adiponectin mRNA expression decreased with obesity in both TNBS groups in intestine and mesenteric fat. Our data suggest an association between preexisting obesity and the exacerbation of TNBS-induced intestinal inflammation. In addition the inflammatory changes observed in fat tissue may reflect changes in metabolic responses associated with proper adipocyte function. Overall, our results may reflect conditions that are important for future approaches in the treatment of human diseases with a similar pathophysiologic basis such as inflammatory bowel disease (IBD).
a Principal Investigator