Mesenteric Adipocyte Dysfunction in Crohn's Disease is Associated with Hypoxia

Background: Abnormalities in mesenteric adipose tissue (MAT) have long been recognized; however, the functional changes in the mesenteric adipocytes as well as the underlying mechanisms are not entirely clear. The aim of this study was to analyze the function and morphology of the MAT in patients with Crohn's disease (CD) and the underlying mechanism. Methods: The MAT specimens were obtained from areas adjacent to the intestinal wall in patients with CD (n = 33) and without CD (control, n = 23) who underwent intestinal resection. For patients with CD, paired samples were obtained from the macroscopically hypertrophic mesenteric adipose tissue (htMAT), adjacent to the involved ileum, and the macroscopically normal mesenteric adipose tissue (nMAT), contiguous with the healthy segment of the ileum. Morphological and molecular techniques were used to detect the characteristics of the MAT of CD and compare them with the characteristics of the control tissues. Hypoxia was confirmed by a high expression of hypoxia-inducible factor 1 alpha. Results: The function and morphology of the nMAT in patients with CD were similar to those of the control tissues. htMAT of CD was dysfunctional based on the evidence that htMAT exhibited decreased lipid store, fatty acid synthase, and adipose triglyceride lipase, but increased levels of glucose transporter 1, aldolase C, and lactate when compared with those from nMAT and control tissues (P < 0.01). In addition, the structure of htMAT was found to be disorganized and characterized by higher levels of collagen content, interleukin 1 beta, interleukin 6, tumor necrosis factor a, and MCP-1 when compared with nMAT and control tissues (P < 0.01). htMAT was in a hypoxic condition, based on the findings that htMAT had a higher level of hypoxia-inducible factor 1 alpha and alpha decreased number of vessels per adipocyte compared with those of nMAT and the control tissues (P < 0.01). The transforming growth factor beta/Smad and nuclear factor-kappa B signaling pathways were found to be activated in htMAT, which may be associated with hypoxia. Conclusions: The disorganized structure and dysfunction of mesenteric adipocyte tissue in CD was confirmed, and these alterations may be associated with hypoxia. It is possible that amelioration of mesenteric adipocyte hypoxia may help attenuate CD with underlying MAT inflammation.