Is Crohn's Creeping Fat an Adipose Tissue?

Background: In human pathology, the creeping fat (CF) of the mesentery is unique to Crohn's disease (CD). CF is usually referred to as an ectopic extension of mesenteric adipose tissue (MAT). However, since no animal model developing CF has ever been established, very little is known about this type of fat-depot expansion and its role in the development of the disease. Methods: We developed and standardized an experimental protocol in mice that reproducibly induces CF development when a severe colonic inflammation is obtained by intracolonic instillation of DNBS. Results: Macro-microscopic observations revealed a fatty appearance of CF. Yet when compared to MAT from the same animals, CF contains very little triglycerides, few adipocytes, and we observed a very low expression and protein levels of both adipose markers (hormone-sensitive lipase, perilipin) and adipocytokines (leptin, adiponectin). The decreased expression of perilipin in CF was also observed by immunohistochemistry. Conversely, the expression of proinflammatory and fibrous markers (Pref-1) was much higher in CF than in MAT. These observations were fully consistent with those made on CF recovered from five CD patients and compared with subcutaneous and mesenteric fat from the same patients. Conclusions: Altogether, this work reports an original experimental mice model of CF. In this model we establish for the first time that CF only occurs in severe colonic inflammation and shows an inflammatory, fibrous but not an adipose pattern.