title: Interaction of osteopontin with IL-18 in obese individuals: implications for insulin resistance.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Immunology and Innovative Cell Therapy Unit, Dasman Diabetes Institute, Kuwait City, Kuwait. rasheed.ahmad@dasmaninstitute.org
authors.forename: Rasheed
authors.initials: R
authors.lastname: Ahmad
authors.forename: Anfal
authors.initials: A
authors.lastname: Al-Mass
authors.forename: Dalal
authors.initials: D
authors.lastname: Al-Ghawas
authors.forename: Nada
authors.initials: N
authors.lastname: Shareif
authors.forename: Nadia
authors.initials: N
authors.lastname: Zghoul
authors.forename: Motasem
authors.initials: M
authors.lastname: Melhem
authors.forename: Amal
authors.initials: A
authors.lastname: Hasan
authors.forename: Fahad
authors.initials: F
authors.lastname: Al-Ghimlas
authors.forename: Said
authors.initials: S
authors.lastname: Dermime
authors.forename: Kazem
authors.initials: K
authors.lastname: Behbehani
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020382:Interleukin-18 / Q000097:blood* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000503:physiopathology; D053495:Osteopontin / Q000097:blood* / Q000235:genetics; D050507:Subcutaneous Fat, Abdominal / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020382:Interleukin-18; D053495:Osteopontin