Journal Article

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

Lewis, Eli C., van Diepen, Janna A., Boekschoten, Mark V., Müller, Michael, Joosten, Leo A. B., Li, Suzhao, Moschen, Alexander R., Bufler, Philip, Tilg, Herbert, Netea, Mihai G., Kim, SooHyun, Dinarello, Charles A., Eini, Hadar, Tack, Cees J., Hijmans, Anneke, Leenders, Floris, Stienstra, Rinke, Ballak, Dov B., Jansen, Henry J., Groenhof, Gert-Jan, Kersten, Sander

2014

Overview

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. Inflammation is a hallmark of obesity and driver of various associated pathologies. Here the authors show that mice overexpressing the anti-inflammatory cytokine IL-37 are protected from the metabolic consequences of a high-fat diet, and that plasma levels of IL-37 correlate with insulin sensitivity in humans.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/1 / 13/21 / 13/31 / 13/51 / 14/63 / 38/61 / 38/77 / 631/250/127/1213 / 631/250/256 / 64/60 / 692/699/317 / Adipocytes - drug effects / Adipocytes - metabolism / Adipocytes - pathology / Adiponectin - blood / Adiponectin - genetics / Adipose tissue / Adipose Tissue - metabolism / Adipose Tissue - pathology / AMP-Activated Protein Kinases - genetics / AMP-Activated Protein Kinases - metabolism / Animals / beta-cells / Diabetes Mellitus, Type 2 - genetics / Diabetes Mellitus, Type 2 - metabolism / Diabetes Mellitus, Type 2 - pathology / Diet, High-Fat / Dietary Fats - adverse effects / expression / family / Gene Expression / Glucose Tolerance Test / high-fat diet / human interleukin-1-alpha / Humanities and Social Sciences / Humans / Inflammation - genetics / Inflammation - metabolism / Inflammation - pathology / innate immunity / Insulin - blood / Insulin - genetics / Insulin Resistance / Interleukin-1 - genetics / Interleukin-1 - metabolism / Interleukin-1 - pharmacology / Macrophages - metabolism / Macrophages - pathology / Male / members / Mice / Mice, Transgenic / multidisciplinary / Obesity / Obesity - etiology / Obesity - genetics / Obesity - metabolism / Obesity - pathology / Primary Cell Culture / receptor / Science / Science (multidisciplinary) / white adipose-tissue