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Severe obesity increases adipose tissue expression of interleukin-33 and its receptor ST2, both predominantly detectable in endothelial cells of human adipose tissue

International Journal of Obesity volume 37, pages 658–665 (2013)Cite this article

Subjects

Abstract

Objective:

Obesity is associated with chronic inflammation of the adipose tissue, which contributes to obesity-associated complications such as insulin resistance and type 2 diabetes. Interleukin (IL)-33 acts via its receptor ST2 and is involved in the pathogenesis of inflammatory disorders including atherosclerosis and heart disease. IL-33 has been demonstrated to promote endothelial cell inflammatory response, but also anti-inflammatory and protective actions such as TH2 and M2 polarization of T cells and macrophages, respectively. IL-33 and ST2 have been shown to be expressed in human and murine adipose tissue. Our objective was to investigate alterations in obesity and a possible role of IL-33 in adipose tissue inflammation.

Subjects and methods:

We investigated severely obese patients (BMI>40 kg m−2, n=20) and lean to overweight controls (BMI<30 kg m−2; n=20) matched for age and sex, as well as diet-induced obese and db/db mice, in order to determine the impact of obesity on IL-33 and ST2 gene and protein expression levels in adipose tissue and blood, and their correlation with inflammatory and metabolic parameters. Furthermore, we examined the cellular source and location of IL-33 and ST2 in situ.

Results:

IL-33 and ST2 expression levels were markedly elevated in omental and subcutaneous adipose tissue of severely obese humans and in diet-induced obese mice, but not in leptin receptor-deficient db/db mice. In addition, soluble ST2, but not IL-33 serum levels, were elevated in obesity. The main source for IL-33 in adipose tissue were endothelial cells, which, in humans, exclusively expressed ST2 on their surface. IL-33 expression strongly correlated with leptin expression in human adipose tissue.

Conclusions:

Expression of IL-33 and its receptor ST2 in human adipose tissue is predominantly detectable in endothelial cells and increased by severe obesity indicating an autocrine action. Thus, the adipose tissue microvasculature could participate in obesity-associated inflammation and related complications via IL-33/ST2.

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Acknowledgements

This work was supported by the Austrian National Bank (ÖNB; project no. 12735), the European Community’s 7th Framework Program (FP7/2007–2013) under grant agreement no. 201608, the Christian Doppler Forschungsgesellschaft (all to TMS), and the Austrian Science Fund (FWF; project no. P18776-B11 to TMS and T445-B11 to SD). We would like to thank Marion Gröger and Sabine Rauscher from the Imaging Core Facility of the Medical University of Vienna for their cooperation in confocal microscopy.

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Authors and Affiliations

  1. Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria

    M Zeyda, B Wernly, M Schranz, A Neuhofer, B K Itariu & T M Stulnig

  2. Christian Doppler-Laboratory for Cardio-Metabolic Immunotherapy, Medical University of Vienna, Vienna, Austria

    M Zeyda, M Schranz, A Neuhofer & T M Stulnig

  3. Department of Internal Medicine II, Clinical Division of Cardiology, Medical University of Vienna, Vienna, Austria

    S Demyanets, C Kaun & J Wojta

  4. Institute of Clinical Pathology, Medical University of Vienna, Vienna, Austria

    M Hämmerle & B Hantusch

  5. Department of Surgery, Medical University of Vienna, Vienna, Austria

    M Keck & G Prager

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  1. M Zeyda
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Correspondence to M Zeyda.

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Zeyda, M., Wernly, B., Demyanets, S. et al. Severe obesity increases adipose tissue expression of interleukin-33 and its receptor ST2, both predominantly detectable in endothelial cells of human adipose tissue. Int J Obes 37, 658–665 (2013). https://doi.org/10.1038/ijo.2012.118

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