Department of Medicine, Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands.
Children's Hospital, Ludwig-Maximilians University, Munich D-80337, Germany.
Nat Commun. 2014 Sep 3;5:4711. doi: 10.1038/ncomms5711.
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.
白细胞介素-1 家族细胞因子是肥胖引起的炎症和全身胰岛素抵抗发展的重要调节剂。在这里，我们表明，白细胞介素-1 家族成员白细胞介素-37（IL-37）最近被表征为一种抗炎细胞因子，可改善肥胖引起的炎症和胰岛素抵抗。人白细胞介素-37（IL-37tg）转基因小鼠表现出脂肪组织巨噬细胞数量减少，循环中脂联素水平增加，16 周高脂肪饮食后葡萄糖耐量和胰岛素敏感性保持不变。体外用重组白细胞介素-37 处理脂肪细胞可减少脂肪生成并激活 AMPK 信号通路。在人类中，稳态 IL-37 脂肪组织 mRNA 水平与胰岛素敏感性呈正相关，并且脂肪组织的炎症状态较低。这些发现表明，IL-37 是肥胖引起的炎症和胰岛素抵抗中在小鼠和人类中重要的抗炎调节剂，并表明 IL-37 是治疗肥胖引起的胰岛素抵抗和 2 型糖尿病的潜在靶点。
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