The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance.
The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance.
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作者：
在没有明显感染或自身免疫过程的情况下，肥胖期间出现慢性“无菌”炎症是一个令人困惑的现象。Nod样受体（NLR）家族的先天免疫细胞传感器如Nlrp 3炎性体涉及识别某些非微生物来源的“信号”，导致半胱天冬酶-1活化和随后的IL-1β和IL-18分泌。我们发现，脂肪组织中Nlrp 3表达的减少与肥胖2型糖尿病患者炎症的减少和胰岛素敏感性的改善有关。Nlrp 3炎性小体感知脂毒性相关的神经酰胺以诱导巨噬细胞和脂肪组织中的半胱天冬酶-1裂解。Nlrp 3的消融阻止了脂肪库和肝脏中肥胖诱导的炎性小体活化以及增强的胰岛素信号传导。此外，肥胖症中Nlrp 3的消除降低了IL-18和脂肪组织IFNγ沿着幼稚脂肪组织T细胞的增加和效应脂肪组织T细胞的减少。总的来说，这些数据确定Nlrp 3炎性小体感知肥胖相关的“肥胖信号”，并有助于肥胖诱导的炎症和胰岛素抵抗。
Emergence of chronic ‘sterile’ inflammation during obesity in absence of overt infection or autoimmune process is a puzzling phenomenon. The Nod Like Receptor (NLR) family of innate immune cell sensors like the Nlrp3 inflammasome are implicated in recognizing certain non-microbial origin ‘danger–signals’ leading to caspase-1 activation and subsequent IL-1β and IL-18 secretion. We show that reduction in adipose tissue expression of Nlrp3 is coupled with decreased inflammation and improved insulin–sensitivity in obese type-2 diabetic patients. The Nlrp3 inflammasome senses the lipotoxicity–associated ceramide to induce caspase-1 cleavage in macrophages and adipose tissue. Ablation of Nlrp3 prevented the obesity–induced inflammasome activation in fat depots and liver together with enhanced insulin–signalling. Furthermore, elimination of Nlrp3 in obesity reduced IL-18 and adipose tissue IFNγ along with an increase in naïve and reduction in effector adipose tissue T cells. Collectively, these data establish that Nlrp3 inflammasome senses obesity–associated ‘danger–signals’ and contributes to obesity–induced inflammation and insulin–resistance.
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影响因子：
82.9
作者：
Arkan, MC;Hevener, AL;Karin, M
通讯作者：
Karin, M
影响因子：
5.5
作者：
Dixit, Vishwa Deep
通讯作者：
Dixit, Vishwa Deep
影响因子：
30.5
作者：
通讯作者：
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DOI：
10.1038/nri2587
发表时间：
2009-08
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.2
作者：
Kummer, J. Alain;Broekhuizen, Roel;Tschopp, Juerg
通讯作者：
Tschopp, Juerg