BACKGROUND & AIMS: Abnormalities of fat in the mesentery including adipose tissue hypertrophy and fat wrapping have been long recognized on surgical specimens as characteristic features of Crohn's disease. However, the importance, origin, and significance of the mesenteric fat hypertrophy in this chronic inflammatory disease are unknown. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a crucial factor involved in the homeostasis of adipose tissue, a major source of biologically active mediators. METHODS: Intra-abdominal fat accumulation was quantified using a magnetic resonance imaging method in patients with Crohn's disease and controls. PPARgamma and inflammatory cytokines synthesized by mesenteric adipose tissues were assessed by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. RESULTS: In vivo, patients with Crohn's disease have an important accumulation of intra-abdominal fat. This mesenteric obesity, present from the onset of the disease, is associated with overexpression of PPARgamma and tumor necrosis factor (TNF)-alpha, synthesized, at least in part, by adipocytes. CONCLUSIONS: These results suggest that confined increased PPARgamma mesenteric concentrations could lead to the mesenteric fat hypertrophy, which could actively participate through the synthesis of TNF-alpha in the inflammatory response.