The ATP-P2X7 signaling axis is dispensable for obesity-associated inflammasome activation in adipose tissue.
The ATP-P2X7 signaling axis is dispensable for obesity-associated inflammasome activation in adipose tissue.
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作者：
Sun S;Xia S;Ji Y;Kersten S;Qi L
脂肪组织中的炎性小体活化与肥胖相关的胰岛素抵抗和2型糖尿病有关。然而，炎性体在脂肪组织中的激活时间和方式仍是推测性的。在这里，我们验证了一个假设，即细胞外ATP，一种通过嘌呤能受体P2X，配体门控离子通道7 （P2X7）对巨噬细胞内炎性小体的有效刺激，可能在肥胖脂肪组织中的炎性小体激活中发挥作用。我们的数据显示，在饲喂60%高脂饲料（HFD） 8周后，脂肪组织中的炎性体被激活，与高血糖和高胰岛素血症的发生以及脂肪组织中P2X7的诱导一致。出乎意料的是，与野生型对照相比，HFD中的p2x7缺陷动物在代谢表型、炎症反应或炎性体激活方面没有表现出变化。在骨髓移植产生的造血细胞特异性p2x7缺陷动物中也获得了类似的观察结果。因此，我们得出结论，肥胖患者脂肪组织中的炎性体激活与高血糖和高胰岛素血症的发病相吻合，但出乎意料的是，它不是由ATP-P2X7信号轴介导的。肥胖患者脂肪组织中炎症小体激活危险信号的性质仍有待研究。
Inflammasome activation in adipose tissue has been implicated in obesity-associated insulin resistance and type 2 diabetes. However, when and how inflammasome is activated in adipose tissue remains speculative. Here we test the hypothesis that extracellular ATP, a potent stimulus of inflammasome in macrophages via purinergic receptor P2X, ligand-gated ion channel, 7 (P2X7), may play a role in inflammasome activation in adipose tissue in obesity. Our data show that inflammasome is activated in adipose tissue upon 8-week feeding of 60% high-fat diet (HFD), coinciding with the onset of hyperglycemia and hyperinsulinemia as well as the induction of P2X7 in adipose tissue. Unexpectedly, P2X7-deficient animals on HFD exhibit no changes in metabolic phenotypes, inflammatory responses, or inflammasome activation when compared with the wild-type controls. Similar observations have been obtained in hematopoietic cell–specific P2X7-deficient animals generated by bone marrow transplantation. Thus, we conclude that inflammasome activation in adipose tissue in obesity coincides with the onset of hyperglycemia and hyperinsulinemia but, unexpectedly, is not mediated by the ATP-P2X7 signaling axis. The nature of the inflammasome-activating danger signal(s) in adipose tissue in obesity remains to be characterized.
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影响因子：
29
作者：
Lichtenstein L;Mattijssen F;de Wit NJ;Georgiadi A;Hooiveld GJ;van der Meer R;He Y;Qi L;Köster A;Tamsma JT;Tan NS;Müller M;Kersten S
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Enjyoji, Keiichi;Kotani, Ko;Thukral, Chandrashekar;Blumel, Benjamin;Sun, Xiaofeng;Wu, Yan;Imai, Masato;Friedman, David;Csizmadia, Eva;Bleibel, Wissam;Kahn, Barbara B.;Robson, Simon C.
通讯作者：
Robson, Simon C.
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影响因子：
56.9
作者：
HOTAMISLIGIL, GS;SHARGILL, NS;SPIEGELMAN, BM
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SPIEGELMAN, BM