Mesenteric Fat in Crohn’s Disease
Florian Rieder, MD, Cleveland Clinic, OH, USA
Accumulating evidence suggests a connection between changes in the mesenteric fat and inflammatory intestinal diseases including IBD, in particular Crohn’s disease 1-4. Anatomically the mesenteric fat is directly connected with the intestinal serosa and muscularis propria and is continuous along the axis of most of the small and large bowel 5, 6. Mesenteric fat wrapping around the circumference of the intestine, so called “creeping fat,” is pathognomonic of CD 1, 7. It sometimes covers more than 50% of the bowel. Recently, the mesenteric and creeping fat in Crohn’s disease has been implicated in its pathogenesis. It contains not only fat cells and their precursors, but also immune cells and non-immune cells, such as endothelial cells and fibroblasts8. These cell types are activated and creeping fat is now known to be an active participant in inflammation and immunity15.
Clinically there is an overlap between intestinal and mesenteric changes on a histopathologic and radiologic level. Mucosal, transmural, serosal and mesenteric alterations are coupled and in the transition zone from normal to abnormal segments all tissue layers change in parallel. This could explain in part the typical transmural nature of the disease 9. Furthermore, creeping fat is associated with muscularis propria hyperplasia and stricturing disease10.
Currently, no mesenteric fat targeted therapies exist, but accumulating evidence suggests that modulation of mesenteric fat mass may influence disease. In a small retrospective study increased visceral fat area was associated with attenuated mucosal healing after anti-TNF therapy in biologically naïve Crohn’s disease patients11. Visceral adiposity as measured by visceral adipose tissue volume may influence the natural history of disease as shown by an association of increased fat with an increased risk of penetrating disease and surgery in CD12. Mesenteric fat may influence the perioperative setting as well. Fat subtype and distribution (subcutaneous-to-visceral fat volume ratio) were found to be predictive of postoperative infectious complications after bowel resection for CD13. Visceral adiposity on cross sectional imaging was found to be an independent risk factor for endoscopic recurrence in post-operative Crohn’s disease14.
The questions remains, does the modulation of mesenteric fat affect outcome? In an excellent study by Coffey et al. surgical recurrence rates after ileocolonic resection for Crohn’s disease were evaluated. In patients with more extensive excision of the mesentery compared to patients with conventional ileocolic resection with limited mesenteric resection the cumulative reoperation rates were 2.9% and 40% respectively. Advanced mesenteric disease predicted increased surgical recurrence15. Interestingly, once present, creeping fat does not seem to change with anti-inflammatory therapy, at least in the short term. Despite endoscopic or transmural healing on MRE, creeping fat was unchanged pre- and post-treatment with anti-TNF therapy or autologous hematopoietic stem-cell transplantation16.
While compelling data is accumulating, at this time it is premature to include radiologic or surgical findings of mesenteric changes as a factor into clinical decision making. Future studies should focus on specific features of CD that are strongly associated with changes in the mesentery 17. Special emphasis should be put on further evaluation of the impact of mesenteric and creeping fat on the response to therapy and natural history of disease, and ultimately its relevance will need to be tested in prospective intervention studies.
References
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