Characterization of mesocolic adipose hyperplasia in a rat 2,4,6-trinitrobenzenesulfonic acid colitis model and comparison to creeping fat in Crohn disease.

Abstract

BACKGROUND: Creeping fat (CrF) has emerged as a key pathological feature of Crohn disease (CD). Available data suggest that microbial translocation in CD may trigger CrF development, potentially exacerbating intestinal inflammation and disrupting homeostasis. However, the role of CrF in disease progression remains poorly understood, raising the need for experimental models. METHODS: Colitis was induced using 2,4,6-trinitrobenzenesulfonic acid (TNBS) in Sprague-Dawley rats kept in conventional housing conditions. Colonoscopy and weight follow-up observations were performed 3 and 5 days after colitis induction. Samples were collected at day 5 for histopathological staining and cytokine gene expression analyses. RESULTS: Mesocolic adipose hyperplasia resembling CrF-like mesentery was present in both male and female TNBS-treated rats, with no significant sex-related variation in prevalence. Endoscopic evaluation revealed that only TNBS-treated rats with a colonoscopic score greater than 7 (out of 9) exhibited a significant presence of a CrF-like mesentery. Furthermore, a strong correlation was observed between the severity of colonic inflammation and the presence of CrF-like mesentery, including hyperplastic adipocytes, increased immune cell infiltration, and fibrosis. Molecular characterization showed an upregulation of key inflammatory cytokines-interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α-and the pathogen-recognition receptors-Toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2)-in the CrF-like mesocolon, as observed in human CrF. Finally, animals exhibiting CrF-like mesocolon showed a translocation of Gram-positive cocci in the subserosal layer. CONCLUSIONS: Mesocolic hyperplasia, closely replicating the key histopathological and molecular features of CD-related CrF, developed in half of the rats in this model. This model provides a cost-effective platform for studying the interplay between intestinal inflammation and mesenteric adipose tissue remodeling.