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

• Published in: International Journal of Obesity Vol. 37; no. 5; pp. 658 - 665
• Main Authors: ZEYDA, M, WERNLY, B, PRAGER, G, WOJTA, J, STULNIG, T. M, DEMYANETS, S, KAUN, C, HÄMMERLE, M, HANTUSCH, B, SCHRANZ, M, NEUHOFER, A, ITARIU, B. K, KECK, M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.05.2013
• Subjects: Adipocytes; Adipose tissues; Animals; Atherosclerosis; Atherosclerosis - metabolism; Biological and medical sciences; Body fat; Complications and side effects; Cytokine receptors; Cytokines; Diabetes; Diabetes Mellitus, Type 2 - metabolism; Endocrinology; Endothelial Cells - immunology; Female; Health aspects; Humans; Immunohistochemistry; Inflammation - immunology; Inflammation - metabolism; Inflammation - physiopathology; Insulin Resistance; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Interleukins; Interleukins - metabolism; Internal medicine; Intra-Abdominal Fat - metabolism; Intra-Abdominal Fat - pathology; Male; Medical sciences; Metabolic diseases; Metabolism; Mice; Mice, Inbred C57BL; Obesity; Obesity, Morbid - immunology; Obesity, Morbid - metabolism; Obesity, Morbid - physiopathology; Omentum - pathology; Physiological aspects; Proteins; Receptors, Cell Surface - metabolism; Receptors, Interleukin - metabolism; Risk factors; Subcutaneous Fat - metabolism; Subcutaneous Fat - pathology; Tumor necrosis factor-TNF; Type 2 diabetes; Austria; Endothelial cell; endothelial cells; Adipose tissue; adipose tissue inflammation; Interleukin; db/db mice; high-fat diet-induced murine obesity; Nutritional status; Human; Obesity; human severe obesity; Rodentia; Nutrition disorder; Cytokine; Metabolic diseases; Increase; Inflammation; Adipokine; Gene expression; Feeding; Vertebrata; Mammalia; Diet; Mouse; Animal; Leptin; Fat; Severe
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2012.118

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. 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. 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. 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.