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.

中文翻译：

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IL-20 通过调节脂肪生成和巨噬细胞失调参与肥胖

IL-20 是 IL-10 家族的促炎细胞因子，与多种疾病有关。然而，IL-20 在肥胖中的调节作用尚不清楚。我们通过 ELISA、Western blotting 和流式细胞术探讨了 IL-20 在肥胖诱导的胰岛素抵抗的发病机制中的作用。在小鼠模型中分析了 IL-20 单克隆抗体 7E 改善饮食诱导的肥胖症的治疗潜力。在肥胖患者中检测到更高的血清 IL-20 水平。它在瘦素缺乏 ( ob / ob )、瘦素抵抗 ( db / db ) 和高脂肪饮食 (HFD) 诱导的小鼠肥胖模型中被上调。体外，IL-20调节脂肪细胞分化和骨髓来源的巨噬细胞极化为促炎性M1型。它还通过上调巨噬细胞中的 TNF-α、单核细胞趋化蛋白 1 (MCP-1)、netrin 1 和 unc5b（netrin 受体）以及脂肪细胞中的 netrin 1、瘦素和 MCP-1 的表达，在脂肪组织中引起炎症和巨噬细胞滞留。IL-20 通过 SOCS-3 途径抑制成熟脂肪细胞中的葡萄糖摄取，从而促进胰岛素抵抗。在 HFD 诱导的肥胖小鼠中，7E 治疗减轻了体重并改善了葡萄糖耐量和胰岛素敏感性；它还减少了局部炎症和脂肪组织中 M1 样巨噬细胞的数量。我们已经确定了 IL-20 在肥胖引起的炎症和胰岛素抵抗中的关键作用，