Adipose tissue inflammation during acute colitis.

<p>(A) Colons and adipose tissue [mesenteric (MAT), epididymal (EAT), and subcutaneous (SAT)] from mice sacrificed at Day 0 and Day 7 (<i>n</i> = 4 per timepoint) were analyzed for relative mRNA expression of TNF-α, IL-1β, and IL-6. Target gene expression was normalized to HPRT gene expression; fold change was calculated relative to mean SAT expression at Day 0. Data represent mean ± SD. ***<i>P</i><0.001, **<i>P</i><0.01, *<i>P</i><0.05 vs. Day 0 of the same tissue; †††<i>P</i><0.001, ††<i>P</i><0.01 vs. EAT and SAT at Day 7; ###<i>P</i><0.001 vs. MAT at Day 7. (B) H&E stained sections of formalin-fixed MAT, EAT, and SAT from Day 0 and Day 7 of experimental colitis were compared (<i>n</i> = 5 per time point). Representative images are shown (original magnification × 400; arrowhead  =  mononuclear infiltrates; thick arrow  =  fibrotic connective tissue; thin arrow  =  adipocytes).</p

Development and progression of experimental colitis.

<p>Male, 6 month-old C57BL/6 mice (<i>n</i> = 20) were exposed to 2% DSS in drinking water for up to 5 days. Mice were sacrificed at Day 0, 3, 7, and 14 of the experimental period (<i>n</i> = 5 per time point). (A) Daily body weight of mice sacrificed at Day 14; mice sacrificed at earlier time points followed a similar pattern. <i>*P</i><0.05 compared to initial body weight on Day 0. (B) Disease Activity Index (DAI) was calculated at the time of sacrifice based on weight loss, stool blood, and stool consistency. (C) Colons were excised and measured lengthwise. (D) H&E stained sections were graded for Histologic Severity Score. (E) Representative images of colon histology on Day 0, 3, 7, and 14 (original magnification × 100; arrowhead  =  mononuclear infiltrates, thick arrow  =  mucosal ulceration, thin arrow  =  epithelial hyperplasia). Data represent mean ± SD, <i>***P</i><0.001, <i>*P</i><0.05 vs. Day 0.</p

Inflammatory Cytokine Gene Expression in Mesenteric Adipose Tissue during Acute Experimental Colitis

BACKGROUND: Production of inflammatory cytokines by mesenteric adipose tissue (MAT) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Animal models of colitis have demonstrated inflammatory changes within MAT, but it is unclear if these changes occur in isolation or as part of a systemic adipose tissue response. It is also unknown what cell types are responsible for cytokine production within MAT. The present study was designed to determine whether cytokine production by MAT during experimental colitis is depot-specific, and also to identify the source of cytokine production within MAT. METHODS: Experimental colitis was induced in 6-month-old C57BL/6 mice by administration of dextran sulfate sodium (2% in drinking water) for up to 5 days. The induction of cytokine mRNA within various adipose tissues, including mesenteric, epididymal, and subcutaneous, was analyzed by qRT-PCR. These adipose tissues were also examined for histological evidence of inflammation. The level of cytokine mRNA during acute colitis was compared between mature mesenteric adipocytes, mesenteric stromal vascular fraction (SVF), and mesenteric lymph nodes. RESULTS: During acute colitis, MAT exhibited an increased presence of infiltrating mononuclear cells and fibrotic structures, as well as decreased adipocyte size. The mRNA levels of TNF-α, IL-1β, and IL-6 were significantly increased in MAT but not other adipose tissue depots. Within the MAT, induction of these cytokines was observed mainly in the SVF. CONCLUSIONS: Acute experimental colitis causes a strong site-specific inflammatory response within MAT, which is mediated by cells of the SVF, rather than mature adipocytes or mesenteric lymph nodes