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 1α.


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 1β, interleukin 6, tumor necrosis factor α, 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 1α and a decreased number of vessels per adipocyte compared with those of nMAT and the control tissues (P < 0.01). The transforming growth factor β/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.
*Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China; and †Department of Gastroenterology/Hepatology, the Cleveland Clinic Foundation, Cleveland, Ohio.
Lugen
L
Zuo
Yi
Y
Li
Weiming
W
Zhu
Bo
B
Shen
Jianfeng
J
Gong
Zhen
Z
Guo
Wei
W
Zhang
Rong
R
Wu
Lili
L
Gu
Ning
N
Li
Jieshou
J
Li
D017667:Adipocytes / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D015153:Blotting, Western; D016022:Case-Control Studies; D003424:Crohn Disease / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006801:Humans; D000860:Hypoxia / Q000209:etiology* / Q000473:pathology; D007124:Immunoenzyme Techniques; D008297:Male; D008643:Mesentery / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D012333:RNA, Messenger