Interleukin-33 induces protective effects in adipose tissue inflammation during obesity in mice

Miller, A. M., Asquith, D. L., Hueber, A. J., Anderson, L. A., Holmes, W. M. , McKenzie, A. N., Xu, D., Sattar, N. , McInnes, I. B. and Liew, F. Y. (2010) Interleukin-33 induces protective effects in adipose tissue inflammation during obesity in mice. Circulation Research, 107(5), pp. 650-658. (doi:10.1161/CIRCRESAHA.110.218867) (PMID:20634488) (PMCID:PMC4254700)

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Abstract

Rationale: Chronic low-grade inflammation involving adipose tissue likely contributes to the metabolic consequences of obesity. The cytokine interleukin (IL)-33 and its receptor ST2 are expressed in adipose tissue, but their role in adipose tissue inflammation during obesity is unclear. Objective: To examine the functional role of IL-33 in adipose tissues and investigate the effects on adipose tissue inflammation and obesity in vivo. Methods and Results: We demonstrate that treatment of adipose tissue cultures in vitro with IL-33 induced production of Th2 cytokines (IL-5, IL-13, IL-10) and reduced expression of adipogenic and metabolic genes. Administration of recombinant IL-33 to genetically obese diabetic (ob/ob) mice led to reduced adiposity, reduced fasting glucose and improved glucose and insulin tolerance. IL-33 also induced accumulation of Th2 cells in adipose tissue and polarization of adipose tissue macrophages toward an M2 alternatively activated phenotype (CD206+), a lineage associated with protection against obesity-related metabolic events. Furthermore, mice lacking endogenous ST2 fed high-fat diet had increased body weight and fat mass and impaired insulin secretion and glucose regulation compared to WT controls fed high-fat diet. Conclusions: In conclusion, IL-33 may play a protective role in the development of adipose tissue inflammation during obesity.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Professor Foo and McInnes, Professor Iain and Xu, Dr Damo and Holmes, Dr William and Asquith, Dr Darren and Miller, Dr Ashley and Hueber, Dr Axel and Sattar, Professor Naveed
Authors: Miller, A. M., Asquith, D. L., Hueber, A. J., Anderson, L. A., Holmes, W. M., McKenzie, A. N., Xu, D., Sattar, N., McInnes, I. B., and Liew, F. Y.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Circulation Research
Publisher:American Heart Association
ISSN:0009-7330
Published Online:15 July 2010

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
486461The role of IL-35 in infection and inflammationFoo LiewMedical Research Council (MRC)G0801198Infection Immunity and Inflammation Medicine
483611Interleukin-33: A Novel Cytokine in the Inflammation of Atherosclerosis and ObesityAshley MillerBritish Heart Foundation (BHF)FS/08/035/25309III -IMMUNOLOGY
483612Interleukin-33: A Novel Cytokine in the Inflammation of Atherosclerosis and ObesityAshley MillerBritish Heart Foundation (BHF)FS/08/035/25309III -IMMUNOLOGY