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Background <p>Obesity is increasingly recognized as a state of chronic, unresolved inflammation in which the interleukin (IL)-33/suppression of tumorigenicity 2 (ST2) axis may represent a key immunometabolic regulator.</p> Objective <p>We investigated circulating concentrations and adipose tissue expression levels of IL-33 and its soluble receptor sST2 in obesity and type 2 diabetes, and evaluated their functional effects on adipocytes and macrophages.</p> Results <p>Circulating IL-33 levels were significantly elevated (<i>P</i> &lt; 0.01) in obesity compared with controls, being positively (<i>P</i> &lt; 0.01) correlated with body mass index and HOMA-IR and negatively (<i>P</i> &lt; 0.05) with HDL cholesterol. Conversely, sST2 was reduced in obesity (<i>P</i> &lt; 0.05) and inversely associated with body fat percentage (<i>P</i> &lt; 0.001) and fibrinogen levels (<i>P</i> &lt; 0.05), suggesting enhanced IL-33 bioavailability. Visceral adipose tissue (VAT) from subjects with obesity exhibited increased IL-33 gene and protein expression levels (<i>P</i> &lt; 0.01, for both). Functional analyses show that IL-33 induced (<i>P</i> &lt; 0.01) the expression of adiponectin, omentin (<i>ITLN1</i>), and <i>IL13</i> in adipocytes and attenuated (<i>P</i> &lt; 0.01) LPS-driven <i>IL1B</i> and <i>TNF</i> expression. In macrophages, adipocyte-conditioned medium (ACM) from people with obesity strongly suppressed (<i>P</i> &lt; 0.01) <i>IL33</i> expression, while exogenous IL-33 counteracted pro-inflammatory activation, reducing LPS- and ACM-induced <i>IL1B</i>, <i>IL6</i>, and <i>IL8</i> (all <i>P</i> &lt; 0.01).</p> Conclusion <p>Our findings indicate a dual and a context-dependent role of IL-33 in obesity, while elevated circulating and VAT IL-33 associate with adiposity and metabolic dysfunction, IL-33 may also exert protective effects by dampening macrophage inflammation and promoting anti-inflammatory adipokines.</p>

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Dual and context-dependent role of the interleukin-33/soluble suppression of tumorigenicity 2 axis in obesity and adipose tissue inflammation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月12日

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  • Marcos Casado,
  • Javier Gómez-Ambrosi,
  • Beatriz Ramírez,
  • Sara Becerril,
  • Amaia Rodríguez,
  • Víctor Valentí,
  • Rafael Moncada,
  • Camilo Silva,
  • Javier Escalada,
  • Gema Frühbeck,
  • Victoria Catalán

摘要

Background

Obesity is increasingly recognized as a state of chronic, unresolved inflammation in which the interleukin (IL)-33/suppression of tumorigenicity 2 (ST2) axis may represent a key immunometabolic regulator.

Objective

We investigated circulating concentrations and adipose tissue expression levels of IL-33 and its soluble receptor sST2 in obesity and type 2 diabetes, and evaluated their functional effects on adipocytes and macrophages.

Results

Circulating IL-33 levels were significantly elevated (P < 0.01) in obesity compared with controls, being positively (P < 0.01) correlated with body mass index and HOMA-IR and negatively (P < 0.05) with HDL cholesterol. Conversely, sST2 was reduced in obesity (P < 0.05) and inversely associated with body fat percentage (P < 0.001) and fibrinogen levels (P < 0.05), suggesting enhanced IL-33 bioavailability. Visceral adipose tissue (VAT) from subjects with obesity exhibited increased IL-33 gene and protein expression levels (P < 0.01, for both). Functional analyses show that IL-33 induced (P < 0.01) the expression of adiponectin, omentin (ITLN1), and IL13 in adipocytes and attenuated (P < 0.01) LPS-driven IL1B and TNF expression. In macrophages, adipocyte-conditioned medium (ACM) from people with obesity strongly suppressed (P < 0.01) IL33 expression, while exogenous IL-33 counteracted pro-inflammatory activation, reducing LPS- and ACM-induced IL1B, IL6, and IL8 (all P < 0.01).

Conclusion

Our findings indicate a dual and a context-dependent role of IL-33 in obesity, while elevated circulating and VAT IL-33 associate with adiposity and metabolic dysfunction, IL-33 may also exert protective effects by dampening macrophage inflammation and promoting anti-inflammatory adipokines.