IL‐20 is involved in obesity by modulation of adipogenesis and macrophage dysregulation. Issue 4 (30th August 2021)

• Record Type: Journal Article
• Authors: Hsu, Yu‐Hsiang; Wu, Chih‐Hsing; Chiu, Chiao‐Juno; Chen, Wei‐Ting; Chang, Yi‐Chieh; Wabitsch, Martin; Chang, Ming‐Shi
• Is Part Of: Immunology. Volume 164:Issue 4(2021)
• Page Start: 817
• Page End: 833
• Publication Date: 2021-08-30
• Subjects: cytokines -- inflammation -- insulin resistance -- interleukin 20 -- obesity; Immunology -- Periodicals
• DOI: 10.1111/imm.13403
• Languages: English
• ISSNs: 0019-2805

Abstract

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. Abstract : IL‐20 acts as an important regulator in obesity‐related adipose tissue inflammation and insulin resistance by regulating adipocyte differentiation and affecting macrophage recruitment and polarization.