12: IL-37 protects against obesity-induced inflammation and insulin resistance
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- 作者：Dov B. Ballak ; Suzhao Li ; Janna A. van Diepen ; Alex ; er R. Moschen ; Henry Jansen ; Anneke Hijmans ; Gert-Jan Groenhof ; Philip Bufler ; S ; er Kersten ; Leo A.B. Joosten ; Herbert Tilg ; Charles A. Dinarello ; Mihai G. Netea ; Cees J. Tack ; Rinke Stienstra
- 刊名：Cytokine
- 出版年：2013
- 出版时间：September, 2013
- 年：2013
- 卷：63
- 期：3
- 页码：245-246
- 全文大小：55 K
文摘
IL1b contributes to obesity-induced adipose tissue inflammation and the development of systemic insulin resistance. Another member of the IL1 family, IL37, is primarily an anti-inflammatory cytokine, which reduces systemic as well as local inflammation. In the present study, we investigated whether the anti-inflammatory properties of IL-37 reduce obesity-induced adipose tissue inflammation and improve insulin sensitivity. In human adipose tissue biopsies we observed a higher level of IL-37 expression in adipocytes compared to IL37 in the stromal vascular fraction. IL37 expression was present in both visceral and subcutaneous adipose tissue. Since no mouse homologue for IL-37 has been discovered to date, we studied mice that are transgenic for human IL-37 (IL-37-Tg). Wild-type (WT) and IL37 Tg mice and were fed a 16 week low-fat diet (LFD) or high-fat diet (HFD) to evaluate the role of IL-37 in obesity and insulin resistance. IL-37-Tg mice did not gain weight when compared to WT animals despite equal food and caloric intake (difference in bodyweight gain IL37 Tg versus WT ?41 % ; p < 0.05). This was accompanied by a reduction in adipose tissue macrophages, pro-inflammatory cytokines, and an improvement in glucose tolerance and insulin sensitivity (?26 % AUC; p < 0.05). A short-term HFD study was also performed to investigate whether IL-37 exerted its effect independent of bodyweight differences. Indeed, in addition after 4 days of HFD, IL-37-Tg mice exhibited an improved glucose tolerance compared to WT animals (?21 % AUC; p < 0.05). Importantly, adiponectin plasma levels of IL-37-Tg mice were significantly higher than in WT mice (+114 % ; p < 0.05), which may partly explain the improvement in insulin sensitivity. Additionally, in vitro recombinant IL-37 preserves insulin signalling in a hepatocyte cell line. Notably, in healthy human subjects, steady-state IL-37 expression in subcutaneous adipose tissue was positively associated with insulin sensitivity, lower adipose tissue leptin production and lower inflammatory status of the adipose tissue. In conclusion, we report that IL-37 exerts anti-inflammatory actions, which modulates obesity-induced inflammation and insulin resistance in mice and humans.