12: IL-37 protects against obesity-induced inflammation and insulin resistance

Abstract

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 p p p 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.