Abstract
Thiazolidinediones exert their antidiabetic effect in part by ameliorating chronic inflammation in adipose tissue. However, the precise mechanism of this anti-inflammatory action has remained unclear. We here investigated the effects of the TZD pioglitazone on the lipid mediator profile of adipose tissue in obese diabetic KKAy mice by metabololipidomics analysis based on liquid chromatography and tandem mass spectrometry. Pioglitazone treatment increased the amounts of pro-resolving lipid mediators including lipoxin B4 (LXB4), resolvin E2, and eicosapentaenoic acid as well as reduced those of prostaglandin E2 and 4-hydroxydocosahexaenoic acid in epididymal adipose tissue of KKAy mice. These effects were accompanied by increased expression of genes for the anti-inflammatory proteins arginase 1, interleukin (IL)–13, and IL-10 in this tissue. Pioglitazone also increased LXB4 production in cultured 3T3-L1 adipocytes. Finally, LXB4 increased IL-10 gene expression in adipose tissue explants from KKAy mice. Together, our results suggest that up-regulation of LXB4 may contribute to the anti-inflammatory effect of pioglitazone in obese adipose tissue.
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