IL-20 is involved in obesity by modulation of adipogenesis and macrophage dysregulation.
Immunology
; 164(4): 817-833, 2021 12.
Article
in En
| MEDLINE
| ID: mdl-34403503
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Interleukins
/
Disease Susceptibility
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Adipogenesis
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Macrophages
/
Obesity
Limits:
Adult
/
Aged
/
Aged80
/
Animals
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Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Immunology
Year:
2021
Type:
Article
Affiliation country:
Taiwan