P022 Development of a novel experimental model for studying creeping fat in Crohn's Disease

Abstract Background A characteristic feature of Crohn's disease (CD) is the transformation of mesenteric adipose tissue into creeping fat (CrF), which becomes inflamed and surrounds the transmural lesion. The occurrence of this condition has been associated with the severity of inflammation and post-surgical recurrence. In this study, we present a promising model of CD induced by 2,4,6-trinitro-benzene sulfonic acid (TNBS) that exhibits experimental CrF. This model provides an innovative tool for the development of surgical techniques as well as the implementation of new therapeutic strategies, as it more accurately depicts the nature of the pathology. Methods Acute colitis was induced by intrarectal instillation of TNBS under conventional conditions. Five days after the administration, acute colitis developed (Fig. A). The variation in the percentage of weight compared to the initial weight was analyzed. Clinical activity was assessed through colonoscopy on the third and fifth days based on parameters such as hyperemia, the extension of ulcers, and presence of stenosis. Further, the weight-to-length ratio of the colon, as well as the area of the lesions, was also collected. All obtained data were analyzed in order to identify any possible differences between the sexes or between the groups that presented CrF or not. Results The frequency of CrF occurrence was approximately 50% in both sexes. Even though, females had smaller volume of CrF and a greater presence of fistulas. As compared to controls, the weight of the animals with CrF decreased (Fig. B) and their clinical activity index increased (Fig. C). Moreover, the area of the lesion was significantly increased in the group with CrF as compared with the group without CrF (Fig. D). The CrF group also demonstrated a significant increase in the weight-to-length ratio of the colon. There were no significant differences between the sexes in the aspects mentioned above. Conclusion The group presenting CrF showed a significant increase in all parameters of disease severity analyzed. We would like to emphasize that animals exhibiting severe symptoms by the fifth day were precisely those that manifested the development of CrF. Importantly, it is noteworthy that monitoring the disease through colonoscopy avoids the necessity for the sacrifice of animals, thereby facilitating a reduction in sample size.