TY - JOUR
T1 - Severe obesity increases adipose tissue expression of interleukin-33 and its receptor ST2, both predominantly detectable in endothelial cells of human adipose tissue
AU - Zeyda, M.
AU - Wernly, B.
AU - Demyanets, S.
AU - Kaun, C.
AU - Hämmerle, M.
AU - Hantusch, B.
AU - Schranz, M.
AU - Neuhofer, A.
AU - Itariu, B. K.
AU - Keck, M.
AU - Prager, G.
AU - Wojta, J.
AU - Stulnig, T. M.
N1 - Funding Information:
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.
PY - 2013/5
Y1 - 2013/5
N2 - 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 T H 2 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.
AB - 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 T H 2 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.
KW - adipose tissue inflammation
KW - db/db mice
KW - endothelial cells
KW - high-fat diet-induced murine obesity
KW - human severe obesity
KW - leptin
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U2 - 10.1038/ijo.2012.118
DO - 10.1038/ijo.2012.118
M3 - Article
C2 - 22828942
AN - SCOPUS:84877582160
SN - 0307-0565
VL - 37
SP - 658
EP - 665
JO - International Journal of Obesity
JF - International Journal of Obesity
IS - 5
ER -