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Adipose tissue has been shown to produce a number of inflammatory cytokines and may play a role in the development and progression of several inflammatory diseases. Accumulation of intra-abdominal fat correlates more strongly with inflammatory disease states than does total body fat, suggesting depot-specific differences in the inflammatory potential of adipose tissue. In inflammatory bowel disease specifically, recent clinical studies suggest that patients with increased intra-abdominal fat may suffer a more aggressive clinical course.

Objective: The purpose of the present study was to evaluate the significance of inflammatory cytokine production by various adipose tissue depots during acute experimental colitis.

Methods: Colitis was induced in C57BL mice by addition of 2% dextran sulfate sodium (DSS) to drinking water for 5 days. Mice were sacrificed at Day 3, 7, 14, and 21 following initiation of DSS treatment. Control mice were sacrificed prior to initiation of treatment. Plasma cytokine levels at time of sacrifice were analyzed by multiplex assays. Colonic tissue damage was evaluated histologically by H&E staining. Tissue levels of cytokine mRNA were compared between the colon, 3 adipose tissue depots (mesenteric, epididymal, and subcutaneous), kidney, and liver by qRT-PCR.

Results: Histologic evidence of colitis and significantly increased plasma IL-6 levels were evident by Day 7 and peaked at Day 14. Changes in cytokine expression within the colon occurred earlier, with significant increases in TNF-a, IL-1b, and IL-6 mRNA all evident by Day 3 (P=0.016). Of the cytokines analyzed, IL-6 in the colon exhibited the most profound increase with colitis, with levels at Day 7 increased 230-fold from baseline (P=0.002). Analysis of adipose tissues from this time point revealed that while IL-6 mRNA expression in mesenteric and epididymal adipose tissue was significantly increased compared to controls, 8.6-fold (P=0.016) and 3.8-fold (P=0.004) respectively, no increase in subcutaneous adipose tissue IL-6 mRNA was observed. Multi-tissue analysis at this time point revealed that mesenteric and epididymal adipose tissue expressed significantly more IL-6 mRNA than the kidney or the liver, whose levels of IL-6 did not increase significantly from baseline.

Conclusions: This study demonstrates that intra-abdominal adipose tissue is a major source of IL-6 during acute experimental colitis. The time course analysis suggests that intra-abdominal fat may have a significant impact on plasma IL-6 levels. Unlike the mesentery, the epididymal fat pad is not contiguous with the inflamed bowel and does not contain the venous or lymphatic drainage of the affected bowel. This suggests a tissue-specific response by the intra-abdominal adipose tissue, rather than merely a local lymphoid reaction to tissue damage in the colon.