Skip to main content
Log in

Adult subjects with Prader-Willi syndrome show more low-grade systemic inflammation than matched obese subjects

  • Original Articles
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Aim: Adult subjects with Prader-Willi syndrome (PWS) may show several conditions that are associated with an activation of innate immunity such as obesity, deficient GH secretion or hypogonadism. Our aim was to study whether obese adult PWS subjects show an additional low-grade systemic inflammation (LGSI) in relation to obese adult non-PWS subjects and lean healthy control subjects before and after a standardized liquid meal. Methods: Seven obese adult PWS subjects, 7 matched obese non-PWS subjects and 7 lean healthy control subjects were studied for 6 h from the administration of a standard liquid meal. Results: Compared to non-PWS, PWS subjects showed higher plasma concentrations of C-reactive protein (CRP) (p=0.030), complement component C3 (p=0.018), interleukin(IL)-18 (p=0.048), and IL-6 (p=0.041) that persisted post-prandially elevated for CRP (p<0.0001), C3 (p=0.015), and IL-18 (p=0.003). Tumor necrosis factor(TNF)-α did not differ between the 3 groups. These results were independent from IGF-I levels, homeostasis model assessment index, and body mass index (BMI). In male subjects with PWS, testosterone levels correlated to IL-18 (r=−0,646, p=0.041). Conclusions: Compared to matched non-PWS subjects, the obese PWS subjects in this study showed an additional LGSI that persisted postprandially and was independent from BMI, insulin resistance, and deficient GH secretion. However, in PWS males, high IL-18 levels were related to low testosterone concentrations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Cassidy SB. Prader-Willi syndrome. J Med Genet 1997, 34: 917–23.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  2. Butler MG. Prader-Willi syndrome: current understanding of cause and diagnosis. Am J Med Genet 1990, 35: 319–32.

    Article  PubMed  CAS  Google Scholar 

  3. Holm VA, Cassidy SB, Butler MG, et al. Prader-Willi syndrome: consensus diagnostic criteria. Pediatrics 1993, 91: 398–402.

    PubMed  CAS  Google Scholar 

  4. Bittel DC, Butler MG. Prader-Willi syndrome: clinical genetics, cytogenetics and molecular biology. Expert Rev Mol Med 2005, 7: 1–20.

    Article  PubMed  Google Scholar 

  5. Burman P, Ritzén EM, Lindgren AC. Endocrine dysfunction in Prader-Willi syndrome: a review with special reference to GH. Endocr Rev 2001, 22: 787–99.

    Article  PubMed  CAS  Google Scholar 

  6. Einfeld SL, Kavanagh SJ, Smith A, Evans EJ, Tonge BJ, Taffe J. Mortality in Prader-Willi Syndrome. Am J Ment Retard 2006, 3: 193–8.

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. Van Oostrom AJ, van Wijk JPH, Cabezas MC. Lipaemia, inflammation and atherosclerosis: novel opportunities in the understanding and treatment of atherosclerosis. Drugs 2004, 64 (Suppl 2): 19–41.

    Article  PubMed  Google Scholar 

  9. Fischer CP, Perstrup LB, Berntsen A, Eskild 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: 152–60.

    Article  PubMed  CAS  Google Scholar 

  10. Cassidy SB, Devi A, Mukaida C. Aging in Prader-Willi syndrome: 22 patients over age 30 years. Proc Greenwood Genet Center 1994, 13: 102–3.

    Google Scholar 

  11. Lamb AS, Johnson WM. Premature coronary artery atherosclerosis in a patient with Prader-Willi syndrome. Am J Med Genet 1987, 28: 873–80.

    Article  PubMed  CAS  Google Scholar 

  12. Goldstone AP, Brynes AE, Thomas EL, et al. Resting metabolic rate, plasma leptin concentrations, leptin receptor expression, and adipose tissue measured by whole-body magnetic resonance imaging in women with Prader-Willi syndrome. Am J Clin Nutr 2002, 75: 468–75.

    PubMed  CAS  Google Scholar 

  13. Goldstone AP, Unmehopa UA, Thomas EL, et al. Hypothalamic neuropeptides and regulation of fat mass in Prader-Willi syndrome. In: Eiholzer U, ‚Allemand D, Zipf W, eds. Prader-Willi syndrome as a model for obesity. Basel, Switzerland: Karger; 2003, 31–43.

    Chapter  Google Scholar 

  14. Talebizadeh Z, Butler MG. Insulin resistance and obesity-related factors in Prader-Willi syndrome: comparison with obese subjects. Clin Genet 2004, 67: 230–9.

    Article  Google Scholar 

  15. Heald AH, Anderson SG, Ivison F, Laing I, Gibson JM, Cruickshank K. C-reactive protein and the insulin-like growth factor (IGF)-system in relation to risk of cardiovascular disease in different ethnic groups. Atherosclerosis 2003, 170: 79–86.

    Article  PubMed  CAS  Google Scholar 

  16. Kaushal K, Heald AH, Siddals K, et al. The impact of abnormalities in IGF and inflammatory systems on the metabolic syndrome. Diabetes Care 2004, 27: 2682–8.

    Article  PubMed  CAS  Google Scholar 

  17. Laaksonen DE, Niskanen L, Punnonen K, et al. Sex hormones, inflammation and the metabolic syndrome: a population-based study. Eur J Endocrinol 2003, 149: 601–8.

    Article  PubMed  CAS  Google Scholar 

  18. Twickler TB, Dallinga-Thie GM, Visseren FL, de Vries WR, Erkelens DW, Koppeschaar HPF. Induction of postprandial inflammatory response in adult onset growth hormone deficiency is related to plasma remnant-like particle-cholesterol concentration. J Clin Endocrinol Metab 2003, 88: 1228–33.

    Article  PubMed  CAS  Google Scholar 

  19. Butler MG, Bittel DC, Kibiryeva N, Garg U. C-reactive protein levels in subjects with Prader-Willi syndrome and obesity. Genet Med 2006, 8: 243–8.

    Article  PubMed  CAS  Google Scholar 

  20. Marzullo P, Marcassa C, Campini R, et al. The impact of growth hormone/insulin-like growth factor-I axis and nocturnal breathing disorders on cardiovascular features of adult patients with Prader-Willi syndrome. J Clin Endocrinol Metab 2005, 90: 5639–46.

    Article  PubMed  CAS  Google Scholar 

  21. Höybye C. Inflammatory markers in adults with Prader-Willi Syndrome before and during 12 months growth hormone treatment. Horm Res 2006, 66: 27–32.

    Article  PubMed  CAS  Google Scholar 

  22. Gill JM, Al-Mamari A, Ferrell WR, et al. Effects of prior moderate exercise on postprandial metabolism and vascular function in lean and centrally obese men. J Am Coll Cardiol 2004, 44: 2375–82.

    Article  PubMed  Google Scholar 

  23. van Oostrom AJ, Sijmonsma TP, Verseyden C, et al. Postprandial recruitment of neutrophils may contribute to endothelial dysfunction. J Lipid Res 2003, 44: 576–83.

    Article  PubMed  CAS  Google Scholar 

  24. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997, 20: 1183–97.

    Google Scholar 

  25. Caixàs A, Bashore C, Nash W, Pi-Sunyer FX, Laferrère B. Insulin, unlike food intake, does not suppress ghrelin in human subjects. J Clin Endocrinol Metab 2002, 87: 1902.

    Article  PubMed  Google Scholar 

  26. Caixàs A, Giménez-Palop O, Giménez-Pérez G, et al. Postprandial adiponectin levels are unlikely to contribute to the pathogenesis of obesity in Prader-Willi syndrome. Horm Res 2006, 65: 39–45.

    Article  PubMed  CAS  Google Scholar 

  27. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner R. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28: 412–9.

    Article  PubMed  CAS  Google Scholar 

  28. Laird N, Ware JH. Random-effects model for longitudinal data. Biometrics 1982, 38: 963–74.

    Article  PubMed  CAS  Google Scholar 

  29. Nettleton JA, Steffen LM, Mayer-Davis EJ, et al. Dietary patterns are associated with biochemical markers of inflammation and endothelial activation in the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Clin Nutr 2006, 83: 1369–79.

    PubMed Central  PubMed  CAS  Google Scholar 

  30. Meijssen S, van Dijk H, Verseyden C, Erkelens M, Cabezas MC. Delayed and exaggerated postprandial complement component 3 response in familial combined hyperlipidemia. ArteriosclerThromb Vasc Biol 2002, 22: 811–6.

    Article  CAS  Google Scholar 

  31. Vendrell J, Broch M, Vilarrasa N, et al. Resistin, adiponectin, ghrelin leptin and proinflammatory cytokines: relationships in obesity. Obes Res 2004, 12: 962–71.

    Article  PubMed  CAS  Google Scholar 

  32. Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 2001, 280: E745–51.

    PubMed  CAS  Google Scholar 

  33. Maachi M, Piéroni L, Bruckert E, et al. Systemic low-grade inflammation is related to both circulating and adipose tissue TNF-α, leptin and IL-6 levels in obese women. Int J Obes Relat Metab Disord 2004, 28: 993–7.

    Article  PubMed  CAS  Google Scholar 

  34. López-Bermejo A, Bosch M, Recasens M, et al. Potential role of interleulin-18 in liver disease associated with insulin resistance. Obes Res 2005, 13: 1925–31.

    Article  PubMed  Google Scholar 

  35. 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: 1268–73.

    Article  PubMed  CAS  Google Scholar 

  36. Escobar-Morreale HF, Botella-Carretero JI, Villuendas G, Sancho J, San Millan 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: 806–11.

    Article  PubMed  CAS  Google Scholar 

  37. Goldstone AP, Thomas EL, Brynes AE, et al. Visceral adipose tissue and metabolic complications of obesity are reduced in Prader-Willi syndrome female adults: evidence for novel influences on body fat distribution. J Clin Endocrinol Metab 2001, 86: 4330–8.

    Article  PubMed  CAS  Google Scholar 

  38. Chorostowska-Wynimko J, Radomska D, Plywaczewski R, et al. Disturbed angiogenic activity in sera from obstructive sleep apnea patients. J Physiol Pharmacol 2005, 56 (Suppl 4): 71–7.

    PubMed  Google Scholar 

  39. Blankenberg S, Luc G, Ducimetiere P, et al.;PRIME Study Group. Interleukin-18 and the risk of coronary heart disease in European men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Circulation 2003, 108: 2453–9.

    Article  PubMed  CAS  Google Scholar 

  40. Minoguchi K, Yokoe T, Tazaki T, et al. Increased carotid intima-media thickness and serum inflammatory markers in obstructive sleep apnea. Am J Respir Crit Care Med 2005, 172: 625–30.

    Article  PubMed  Google Scholar 

  41. Kreier F, Fliers E, Voshol PJ, et al. Selective parasympathetic innervation of subcutaneous and intra-abdominal fat—functional implications. J Clin Invest 2002, 110: 1243–50.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. Caixàs MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Caixàs, A., Giménez-Palop, O., Broch, M. et al. Adult subjects with Prader-Willi syndrome show more low-grade systemic inflammation than matched obese subjects. J Endocrinol Invest 31, 169–175 (2008). https://doi.org/10.1007/BF03345585

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03345585

Key Words

Navigation