Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe, Hyogo, 650-0017, Japan.
Division of Epidemiology, Department of Community Medicine and Social Healthcare Science, Kobe, Hyogo, 650-0017, Japan; The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, Kobe, Hyogo, 650-0017, Japan.
Biochem Biophys Res Commun. 2018 Oct 20;505(1):29-35. doi: 10.1016/j.bbrc.2018.09.081. Epub 2018 Sep 17.
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 B (LXB), resolvin E2, and eicosapentaenoic acid as well as reduced those of prostaglandin E 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 LXB production in cultured 3T3-L1 adipocytes. Finally, LXB increased IL-10 gene expression in adipose tissue explants from KKAy mice. Together, our results suggest that up-regulation of LXB may contribute to the anti-inflammatory effect of pioglitazone in obese adipose tissue.
噻唑烷二酮类药物通过改善脂肪组织的慢性炎症发挥其抗糖尿病作用。然而，这种抗炎作用的确切机制仍不清楚。我们通过基于液相色谱和串联质谱的代谢脂质组学分析，研究了 TZD 吡格列酮对肥胖型糖尿病 KKAy 小鼠脂肪组织中脂质介质谱的影响。吡格列酮治疗增加了包括脂氧素 B（LXB）、解析素 E2 和二十碳五烯酸在内的促解决脂质介质的含量，同时降低了前列腺素 E 和 4-羟基二十二碳六烯酸在 KKAy 小鼠附睾脂肪组织中的含量。这些作用伴随着该组织中抗炎蛋白精氨酸酶 1、白细胞介素（IL）-13 和 IL-10 的基因表达增加。吡格列酮还增加了培养的 3T3-L1 脂肪细胞中的 LXB 产生。最后，LXB 增加了来自 KKAy 小鼠脂肪组织外植体的 IL-10 基因表达。总之，我们的结果表明，LXB 的上调可能有助于吡格列酮在肥胖脂肪组织中的抗炎作用。
