IL-20 is involved in obesity by modulation of adipogenesis and macrophage dysregulation.

Abstract

IL-20 is a proinflammatory cytokine of the IL-10 family and involved in several diseases. However, the regulatory role of IL-20 in obesity is not well understood. We explored the function of IL-20 in the pathogenesis of obesity-induced insulin resistance by ELISA, Western blotting and flow cytometry. The therapeutic potential of IL-20 monoclonal antibody 7E for ameliorating diet-induced obesity was analysed in murine models. Higher serum IL-20 levels were detected in obese patients. It was upregulated in leptin-deficient (ob/ob), leptin-resistant (db/db) and high-fat diet (HFD)-induced murine obesity models. In vitro, IL-20 regulated the adipocyte differentiation and the polarization of bone marrow-derived macrophages into proinflammatory M1 type. It also caused inflammation and macrophage retention in adipose tissues by upregulating TNF-α, monocyte chemotactic protein 1 (MCP-1), netrin 1 and unc5b (netrin receptor) expression in macrophages and netrin 1, leptin and MCP-1 in adipocytes. IL-20 promoted insulin resistance by inhibiting glucose uptake in mature adipocytes through the SOCS-3 pathway. In HFD-induced obesity in mice, 7E treatment reduced body weight and improved glucose tolerance and insulin sensitivity; it also reduced local inflammation and the number of M1-like macrophages in adipose tissues. We have identified a critical role of IL-20 in obesity-induced inflammation and insulin resistance, and we conclude that IL-20 may be a novel target for treating obesity and insulin resistance in patients with metabolic disorders.

• Authors: Yu-Hsiang Hsu, Chih-Hsing Wu, Chiao-Juno Chiu, Wei-Ting Chen, Yi-Chieh Chang, Martin Wabitsch, Ming-Shi Chang
• Journal: Immunology (Immunology) Vol. 164 Issue 4 Pg. 817-833 (12 2021) ISSN: 1365-2567 [Electronic] England
• PMID: 34403503 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 John Wiley & Sons Ltd.

Chemical References

• Biomarkers
• Cytokines
• Insulin
• Interleukins
• Glucose
• interleukin 20

Topics

• Adipocytes (metabolism)
• Adipogenesis (genetics)
• Adult
• Aged
• Aged, 80 and over
• Animals
• Biomarkers
• Chemotaxis, Leukocyte
• Cytokines (metabolism)
• Disease Models, Animal
• Disease Susceptibility
• Female
• Gene Expression
• Glucose (metabolism)
• Humans
• Insulin (metabolism)
• Interleukins (genetics, metabolism)
• Macrophages (immunology, metabolism)
• Male
• Mice
• Middle Aged
• Obesity (etiology, metabolism, pathology)
• Signal Transduction