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Increased serum interleukin-18 concentration is associated with hypoadiponectinemia in obesity, independently of insulin resistance

International Journal of Obesity volume 31, pages 221–225 (2007)Cite this article

Abstract

Objective:

Interleukin-18 (IL-18) is a cytokine with proinflammatory and proatherogenic properties, which might be associated with the development of insulin resistance. In contrast, adiponectin, a protein secreted by adipose tissue, might exert insulin-sensitizing and antiatherogenic effects. The aim of the present study was to analyze the association between serum IL-18 and adiponectin in lean and obese subjects, in relation to insulin resistance.

Design:

Cross-sectional study.

Subjects:

One hundred and thirty individuals, 62 lean (body mass index (BMI)<25 kg/m2, 30 men and 32 women) and 68 with overweight or obesity (BMI>25 kg/m2, 24 men and 44 women), with normal glucose tolerance and without concomitant diseases.

Measurements:

Oral glucose tolerance test, euglycemic hyperinsulinemic clamp, serum concentrations of IL-18, IL-6, soluble tumor necrosis factor-α receptors and adiponectin.

Results:

Obese subjects had lower insulin sensitivity (M value, P=0.00029) and serum adiponectin (P=0.01) and higher levels of serum IL-18 (P=0.00055). Circulating IL-18 was negatively related to adiponectin (r=−0.31, P=0.00027) and insulin sensitivity (r=−0.33, P=0.00012). Subgroup analysis revealed that these associations were present in the obese (adiponectin, r=−0.38, P=0.0014; M, r=−0.29, P=0.016), but not in lean individuals (r=−0.17, P=0.18 and r=−0.20, P=0.12, respectively). Association of IL-18 with adiponectin remained significant after adjustment for other estimated parameters, including insulin sensitivity. Also, relationship between IL-18 and insulin sensitivity was independent of other estimated parameters.

Conclusion:

Serum IL-18 is inversely related to serum adiponectin, independently of insulin resistance. The relationships of IL-18 with adiponectin and insulin sensitivity are influenced by the presence of overweight/obesity.

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References

  1. Festa A, D'Agostino Jr R, Howard G, Mykkanen L, Tracy RP, Haffner SM . Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 2000; 102: 42–47.

    Article  CAS  Google Scholar 

  2. Fernandez-Real JM, Ricart W . Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 2003; 24: 278–301.

    Article  CAS  Google Scholar 

  3. Blankenberg S, Luc G, Ducimetiere P, Arveiler D, Ferrieres J, Amouyel P et al. Interleukin-18 and the risk of coronary heart disease in European men. The Prospective Epidemiological Study of Myocardial Infarction (PRIME). Circulation 2003; 108: 2453–2459.

    Article  CAS  Google Scholar 

  4. Blankenberg S, Tiret L, Bickel C, Peetz D, Cambien F, Meyer J et al. Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina. Circulation 2002; 106: 24–30.

    Article  CAS  Google Scholar 

  5. Skurk T, Kolb H, Muller-Scholze S, Rohrig K, Hauner H, Herder C . The proatherogenic cytokine interleukin-18 is secreted by human adipocytes. Eur J Endocrinol 2005; 152: 863–868.

    Article  CAS  Google Scholar 

  6. Wood IS, Wang B, Jenkins JR, Trayhurn P . The pro-inflammatory cytokine IL-18 is expressed in human adipose tissue and strongly upregulated by TNFalpha in human adipocytes. Biochem Biophys Res Commun 2005; 337: 422–429.

    Article  CAS  Google Scholar 

  7. Esposito K, Pontillo A, Ciotola M, Di Palo C, Grella E, Nicoletti G et al. Weight loss reduces interleukin-18 levels in obese women. J Clin Endocrinol Metab 2002; 87: 3864–3866.

    Article  CAS  Google Scholar 

  8. Escobar-Morreale HF, Botella-Carretero JI, Villuendas G, Sancho J, San Milan JL . Serum interleukin-18 concentrations are increased in the polycystic ovary syndrome: relationship to insulin resistance and to obesity. J Clin Endocrinol Metab 2004; 89: 806–811.

    Article  CAS  Google Scholar 

  9. Hung J, McQuillan BM, Chapman CM, Thompson PL, Beilby JP . Elevated interleukin-18 levels are associated with the metabolic syndrome independent of obesity and insulin resistance. Arterioscler Thromb Vasc Biol 2005; 25: 1268–1273.

    Article  CAS  Google Scholar 

  10. Esposito K, Nappo F, Giugliano F, Di Palo C, Ciotola M, Barbieri M et al. Cytokine milieu tends towards inflammation in type 2 diabetes. Diabetes Care 2003; 26: 1647.

    Article  Google Scholar 

  11. Esposito K, Nappo F, Giugliano F, Di Palo C, Ciotola M, Barbieri M et al. Meal modulation of circulating interleukin 18 and adiponectin concentrations in healthy subjects and in patients with type 2 diabetes mellitus. Am J Clin Nutr 2003; 78: 1135–1140.

    Article  CAS  Google Scholar 

  12. Aso Y, Okumura K, Takebayashi K, Wakabayashi S, Inukai T . Relationships of plasma interleukin-18 concentrations to hyperhomocysteinemia and carotid intimal–media wall thickness in patients with type 2 diabetes. Diabetes Care 2003; 26: 2622–2627.

    Article  Google Scholar 

  13. Thorand B, Kolb H, Baumert J, Koenig W, Chambless L, Meisinger C et al. Elevated levels of interleukin-18 predict the development of type 2 diabetes: results from the MONICA/KORA Augsburg study, 1984–2002. Diabetes 2005; 54: 2932–2938.

    Article  CAS  Google Scholar 

  14. Bosch M, Lopez-Bermejo A, Vendrell J, Musri M, Ricart W, Fernandez-Real JM . Circulating IL-18 concentration is associated with insulin sensitivity and glucose tolerance through increased fat-free mass. Diabetologia 2005; 48: 1841–1843.

    Article  CAS  Google Scholar 

  15. Fischer CP, Perstrup LB, Berntsen A, Eskildesn P, Pedersen BK . Elevated plasma interleukin-18 is a marker of insulin-resistance in type 2 diabetic and non-diabetic humans. Clin Immunol 2005; 117: 152–160.

    Article  CAS  Google Scholar 

  16. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001; 7: 941–946.

    Article  CAS  Google Scholar 

  17. Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 2001; 103: 1057–1063.

    Article  CAS  Google Scholar 

  18. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001; 86: 1930–1935.

    Article  CAS  Google Scholar 

  19. Kowalska I, Straczkowski M, Nikolajuk A, Krukowska A, Kinalska I, Gorska M . Plasma adiponectin concentration and TNF-α system activity in lean non-diabetic offspring of type 2 diabetic subjects. Eur J Endocrinol 2006; 154: 319–324.

    Article  CAS  Google Scholar 

  20. DeFronzo RA, Tobin JD, Andres R . Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: E214–E223.

    CAS  PubMed  Google Scholar 

  21. Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 2003; 289: 1799–1804.

    Article  CAS  Google Scholar 

  22. Lindegaard B, Hansen AB, Gerstoft J, Pedersen BK . High plasma level of interleukin-18 in HIV-infected subjects with lipodystrophy. J Acquir Immune Defic Syndr 2004; 36: 588–593.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by the Grant 3 P05A 002 25 from the Polish State Committee for Scientific Research and by the Grant 3-50692 from the Medical University of Bialystok.

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Authors and Affiliations

  1. Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, Białystok, Poland

    M Straczkowski, I Kowalska, A Nikolajuk, E Otziomek, A Adamska, M Karolczuk-Zarachowicz & M Gorska

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  1. M Straczkowski
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  2. I Kowalska
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Correspondence to M Straczkowski.

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Straczkowski, M., Kowalska, I., Nikolajuk, A. et al. Increased serum interleukin-18 concentration is associated with hypoadiponectinemia in obesity, independently of insulin resistance. Int J Obes 31, 221–225 (2007). https://doi.org/10.1038/sj.ijo.0803421

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