IL-37 protects against obesity-induced inflammation and insulin resistance
IL-37 protects against obesity-induced inflammation and insulin resistance
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DOI：
10.1038/ncomms5711
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发表时间：
2014-09-01
影响因子：
16.6
通讯作者：
Stienstra, Rinke
中科院分区：
文献类型：
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作者：
Ballak, Dov B.;van Diepen, Janna A.;Stienstra, Rinke
白细胞介素 - 1（IL - 1）家族的细胞因子是肥胖诱导的炎症以及全身性胰岛素抵抗发展的重要调节因子。在此我们表明，IL - 1家族成员IL - 37，近期被鉴定为一种抗炎细胞因子，可改善肥胖诱导的炎症和胰岛素抵抗。转有人IL - 37基因的小鼠（IL - 37tg）在高脂饮食（HFD）16周后，脂肪组织巨噬细胞数量减少，脂联素循环水平升高，并且糖耐量和胰岛素敏感性得以保留。用重组IL - 37对脂肪细胞进行体外处理可减少脂肪生成并激活腺苷酸活化蛋白激酶（AMPK）信号通路。在人类中，稳态IL - 37脂肪组织mRNA水平升高与胰岛素敏感性以及脂肪组织较低的炎症状态呈正相关。这些发现揭示了IL - 37在小鼠和人类肥胖诱导的炎症及胰岛素抵抗过程中是一种重要的抗炎调节因子，并表明IL - 37是治疗肥胖诱导的胰岛素抵抗和2型糖尿病的一个潜在靶点。
Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here we show that IL-1 family member IL-37, recently characterized as an anti-inflammatory cytokine, ameliorates obesity-induced inflammation and insulin resistance. Mice transgenic for human IL-37 (IL-37tg) exhibit reduced numbers of adipose tissue macrophages, increased circulating levels of adiponectin and preserved glucose tolerance and insulin sensitivity after 16 weeks of HFD. In vitro treatment of adipocytes with recombinant IL-37 reduces adipogenesis and activates AMPK signalling. In humans, elevated steady-state IL-37 adipose tissue mRNA levels are positively correlated with insulin sensitivity and a lower inflammatory status of the adipose tissue. These findings reveal IL-37 as an important anti-inflammatory modulator during obesity-induced inflammation and insulin resistance in both mice and humans, and suggest that IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes.