IL-21 is a major negative regulator of IRF4-dependent lipolysis affecting Tregs in adipose tissue and systemic insulin sensitivity.

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Output type: Journal article

Author list: Fabrizi, Marchetti, Mavilio, Marino, Casagrande, Cavalera, Moreno Navarrete, Mezza, Sorice, Fiorentino, Menghini, Lauro, Monteleone, Giaccari, Fernandez Real, Federici

Publisher: American Diabetes Association

Publication year: 2014

Journal: Diabetes (0012-1797)

Volume number: 63

Issue number: 6

ISSN: 0012-1797

eISSN: 1939-327X

Languages: English-Great Britain (EN-GB)

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Open access status: hybrid

Full text URL: https://diabetes.diabetesjournals.org/content/diabetes/63/6/2086.full.pdf

Abstract

Obesity elicits immune cells infiltration of adipose tissue provoking chronic low-grade inflammation. Regulatory T cells (Tregs) are specifically reduced in adipose tissue of obese animals. Since Interleukin 21 (IL-21) plays an important role in inducing and maintaining immune-mediated chronic inflammatory processes and negatively regulates Tregs differentiation/activity we hypothesized that it could play a role in obesity-induced insulin resistance.We found IL-21 and IL-21R mRNA expression up-regulated in adipose tissue of high fat diet WT mice and in stromal-vascular fraction from human obese subjects in parallel to macrophage and inflammatory markers. Interestingly a larger infiltration of Treg cells was seen in the adipose tissue of IL-21 knockout (IL-21 KO) mice compared to WT animals fed both ND and HFD.In a context of diet-induced obesity, IL-21 KO mice, when compared to WT animals, exhibited lower body weight improved insulin sensitivity and decreased adipose and hepatic inflammation. This metabolic phenotype is accompanied by an higher induction of IRF4, a transcriptional regulator of fasting lipolysis in adipose tissue. Our data suggest that IL-21 exerts negative regulation on IRF4 and Tregs activity, developing and maintaining adipose tissue inflammation in the obesity state.

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