Haoneng Tang1, Ning Liu1,2, Xiaojing Feng1, Yanyi Yang3, Yiyuan Fang1, Siqi Zhuang1, Yufeng Dai1, Meilian Liu4,5, Lingli Tang6. 1. Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, China. 2. Medical College, Yueyang Vocational and Technical College, Yueyang, 414000, China. 3. Health Management Center, The Second Xiangya Hospital, Central South University, Changsha, 410011, China. 4. Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. 5. Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, 410011, China. 6. Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410011, China. linglitang@csu.edu.cn.
Abstract
BACKGROUND: Interleukin-33 (IL-33) plays a pivotal role in regulating innate immune response and metabolic homeostasis. However, whether its circulating level is correlated with obesity and metabolic disorders in humans remains largely unknown. We aimed to address this gap by determining IL-33 serum level and its downstream type 2 inflammatory cytokines interleukin-5 (IL-5) and interleukin-13 (IL-13) in overweight/obese population, and analyzing the specific associations between IL-33 and obesity metabolic phenotypes. METHODS: 217 subjects were enrolled and divided into three groups: healthy control (HC) subjects, metabolically healthy overweight/obese (MHOO) subjects and metabolically unhealthy overweight/obese (MUOO) subjects. Circulating levels of IL-33, IL-5 and IL-13 were measured using ELISA analyses. Multivariate regression analyses were further performed to determine the independent association between IL-33 and obesity metabolic phenotypes. RESULTS: Circulating levels of IL-33 were significantly elevated in subjects of MUOO group compared with HC group and MHOO group, while no significant difference was observed between the latter two groups in IL-33 levels. Consistent with this, serum levels of IL-5/13 were higher in the MUOO group compared with HC and MHOO groups. After adjusted for all confounders, MUOO phenotype was significantly associated with increased IL-33 serum levels (OR = 1.70; 95% CI 1.09-2.64; p = 0.019). With the MHOO group as the reference population, higher circulating level of IL-33 was also positively associated with MUOO phenotype after adjusting for confounders (OR = 1.50; 95% CI 1.20-1.88; p = 2.91E-4). However, there was no significant association between MHOO phenotype and IL-33 levels (p = 0.942). Trend analysis further confirmed the positive correlation between MUOO phenotype and IL-33 level (p for trend = 0.019). Additionally, IL-33 was significantly and positively correlated with diastolic blood pressure (DBP), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), white blood cell (WBC), neutrophil and IL-5 only in MUOO group, while inversely correlated with high density lipoprotein cholesterol (HDL-C) in MHOO subjects. CONCLUSION: Circulating levels of IL-33 were significantly elevated in overweight/obese Chinese adults with metabolic disorders. Increased levels of IL-33 were positively associated with metabolically unhealthy overweight/obese phenotype and several metabolic syndrome risk factors.
BACKGROUND: Interleukin-33 (IL-33) plays a pivotal role in regulating innate immune response and metabolic homeostasis. However, whether its circulating level is correlated with obesity and metabolic disorders in humans remains largely unknown. We aimed to address this gap by determining IL-33 serum level and its downstream type 2 inflammatory cytokines interleukin-5 (IL-5) and interleukin-13 (IL-13) in overweight/obese population, and analyzing the specific associations between IL-33 and obesity metabolic phenotypes. METHODS: 217 subjects were enrolled and divided into three groups: healthy control (HC) subjects, metabolically healthy overweight/obese (MHOO) subjects and metabolically unhealthy overweight/obese (MUOO) subjects. Circulating levels of IL-33, IL-5 and IL-13 were measured using ELISA analyses. Multivariate regression analyses were further performed to determine the independent association between IL-33 and obesity metabolic phenotypes. RESULTS: Circulating levels of IL-33 were significantly elevated in subjects of MUOO group compared with HC group and MHOO group, while no significant difference was observed between the latter two groups in IL-33 levels. Consistent with this, serum levels of IL-5/13 were higher in the MUOO group compared with HC and MHOO groups. After adjusted for all confounders, MUOO phenotype was significantly associated with increased IL-33 serum levels (OR = 1.70; 95% CI 1.09-2.64; p = 0.019). With the MHOO group as the reference population, higher circulating level of IL-33 was also positively associated with MUOO phenotype after adjusting for confounders (OR = 1.50; 95% CI 1.20-1.88; p = 2.91E-4). However, there was no significant association between MHOO phenotype and IL-33 levels (p = 0.942). Trend analysis further confirmed the positive correlation between MUOO phenotype and IL-33 level (p for trend = 0.019). Additionally, IL-33 was significantly and positively correlated with diastolic blood pressure (DBP), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), white blood cell (WBC), neutrophil and IL-5 only in MUOO group, while inversely correlated with high density lipoprotein cholesterol (HDL-C) in MHOO subjects. CONCLUSION: Circulating levels of IL-33 were significantly elevated in overweight/obese Chinese adults with metabolic disorders. Increased levels of IL-33 were positively associated with metabolically unhealthy overweight/obese phenotype and several metabolic syndrome risk factors.
Authors: Waldiceu A Verri; Fabrício O Souto; Silvio M Vieira; Sergio C L Almeida; Sandra Y Fukada; Damo Xu; Jose C Alves-Filho; Thiago M Cunha; Ana T G Guerrero; Rafaela B Mattos-Guimaraes; Fabíola R Oliveira; Mauro M Teixeira; João S Silva; Iain B McInnes; Sergio H Ferreira; Paulo Louzada-Junior; Foo Y Liew; Fernando Q Cunha Journal: Ann Rheum Dis Date: 2010-05-14 Impact factor: 19.103
Authors: Jonathan R Brestoff; Brian S Kim; Steven A Saenz; Rachel R Stine; Laurel A Monticelli; Gregory F Sonnenberg; Joseph J Thome; Donna L Farber; Kabirullah Lutfy; Patrick Seale; David Artis Journal: Nature Date: 2014-12-22 Impact factor: 49.962