Interaction of Osteopontin with IL-18 in Obese Individuals: Implications for Insulin Resistance

PLoS One

Fahad Al-Ghimlas¹  Motasem Melhem²  Nadia Zghoul³  Amal Hasan³  Said Dermime³  Rasheed Ahmad³  Nada Shareif³  Anfal Al-Mass³  Dalal Al-Ghawas³  Kazem Behbehani⁴ 

[1] Fitness and Rehabilitation Center, Dasman Diabetes Institute, Kuwait City, Kuwait;Genetics and Genomics Unit, Dasman Diabetes Institute, Kuwait City, Kuwait;Immunology and Innovative Cell Therapy Unit, Dasman Diabetes Institute, Kuwait City, Kuwait;Senior Management, Dasman Diabetes Institute, Kuwait City, Kuwait

关键词: Obesity;    Adipose tissue;    Body mass index;    Gene expression;    Insulin resistance;    Cytokines;    Inflammatory diseases;    Inflammation;   

DOI  :  10.1371/journal.pone.0063944

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Background/Objective Osteopontin (OPN) and IL-18 are known inflammatory mediators and both participate in a wide range of biological processes linked to immunological disorders. Since an interaction between OPN and IL-18 has not been studied in obesity, we investigated whether: (i) their levels were simultaneously elevated in obese individuals; (ii) OPN was associated with IL-18 in obese individuals and (iii) their levels associated with fasting blood glucose (FBG) and BMI.Subjects and Methods PBMCs and plasma samples were isolated from 60 individuals including lean as well as overweight and obese individuals. Subcutaneous adipose tissue samples were obtained. OPN and IL-18 were measured by ELISA. OPN and IL-18 mRNA expression was quantified by real time quantitative RT-PCR.Results Obese individuals exhibited significantly increased circulating OPN levels as compared with lean individuals (obese 2865±101; lean 1681±116 pg/ml; P<0.0001). IL-18 levels were also high in obese individuals (obese 491±39, lean 301±26 pg/ml; P = 0.0009). OPN and IL-18 expression were simultaneously up-regulated (OPN: 5.4-Fold; IL-18: 8.9-Fold; P<0.05) in PBMCs from obese individuals compared to lean group. Adipose tissue from obese individuals had high expression of OPN (7.3-Fold) and IL-18 (9.6-Fold). Plasma OPN levels correlated positively with FBG levels (r = 0.32, P = 0.02). Similarly, IL-18 correlated positively with FBG levels (r = 0.406, P = 0.0042). Stepwise multiple regression analysis showed an independent association of BMI with OPN and IL-18. Interestingly, OPN levels increased progressively with an increase in IL-18 levels (r = 0.52, P = 0.0004). We also examined the regulatory role of IL-18 in OPN secretion from PBMCs. Neutralizing anti-IL-18Rα mAb reduced OPN secretion.Conclusion These findings represent the first observation that plasma, PBMC and adipose tissue OPN and IL-18 are simultaneously increased and correlate with each other in overweight/obese individuals which may trigger the development of obesity-associated insulin resistance. Moreover, these results provide the direct evidence that IL-18 regulates OPN production in PBMCs.

【 授权许可】

CC BY