Skip to main content

Advertisement

SpringerLink
Log in

Is resistin a link between highly active antiretroviral therapy and fat redistribution in HIV-infected children?

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

Abstract

Objectives: To assess the features of fat redistribution, detected by clinical and ultrasound (US) methods, and the presence of metabolic disorders in HIV-infected children undergoing antiretroviral therapy. To evaluate if serum levels of resistin, a hormone produced only by visceral adipose tissue, are a marker of fat redistribution in these patients. Design and methods: Forty-five consecutive symptomatic HIV-infected children were considered for inclusion in the study. Patients were enrolled if treated for at least 6 months with antiretroviral therapy with or without protease inhibitor (PI) and if compliant to the study protocol. Patients were evaluated for: anthropometric measures, fat redistribution by clinical and US methods, serum lipids, parameters of insulin resistance by homeostasis model assessment for insulin resistance, serum resistin levels by an enzyme-linked immunosorbent assay. Results: Eighteen children fulfilled the inclusion criteria and were enrolled in the study. Twelve (66%) children had clinical and/or US evidence of fat redistribution; 9 (75%) of them were on PI therapy; only 3 of 6 children without fat redistribution were on PI therapy (p<0.05). Serum lipids and insulin resistance parameters did not differ between children with or without fat redistribution. There was a highly significant linear correlation between visceral fat detected by US and circulating resistin levels (r=0.87; p<0.0001). Conclusions: Fat redistribution occurred in most HIV-infected children undergoing PI therapy. Because serum resistin levels reflect the amount of visceral fat, they could be considered a sensitive marker of fat redistribution in HIV-infected children.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet 1999, 353: 2093–9.

    Article  PubMed  CAS  Google Scholar 

  2. McDermott AY, Shevitz A, Knox T, Roubenoff R, Kehayas J, Gorbach S. Effect of highly active antiretroviral therapy on fat, lean, bone mass in HIV-seropositive men and women. Am J Clin Nutr 2001, 74: 679–86.

    PubMed  CAS  Google Scholar 

  3. Bochkorst JL, Ksseriy I, Toye M, et al. Evidence of human immunodeficiency virus associated lipodystrophy syndrome in children with protease inhibitors Pediatr Infect Dis J 2003, 22: 463–5.

    Google Scholar 

  4. Nolan D, Mallal S. Antiretroviral-therapy-associated lipoatrophy: current status and future directions Sex Health 2005, 2: 153–63.

    Article  PubMed  Google Scholar 

  5. Kosmiski L, Kuritzkes D, Lichtenstein K, Eckel R. Adipocyte-derived hormone levels in HIV lipodystrophy Antivir Ther 2003, 8: 9–15.

    PubMed  CAS  Google Scholar 

  6. Ahima RS, Flier JS. Adipose tissue as an endocrine organ. Trends Endocrinol Metab 2000, 11: 327–32.

    Article  PubMed  CAS  Google Scholar 

  7. Bajaj M, Suraamornkul S, Piper P, et al. Decreased plasma adiponectin concentrations are closely related to hepatic fat content and hepatic insulin resistance in pioglitazone-treated type 2 diabetic patients. J Clin Endocrinol Metab 2004, 89: 200–6.

    Article  PubMed  CAS  Google Scholar 

  8. Noor MA, Lo JC, Mulligan K, et al. Metabolic effects of indinavir in healthy HIV-seronegative men. AIDS 2001, 15: F11–8.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  9. Estrada V, Serrano-Rios M, Martinez Larrad MT, et al. Leptin and adipose tissue maldistribution in HIV-infected male patients with predominant fat loss treated with antiretroviral therapy. J Acquir Immune Defic Syndr 2002, 29: 32–40.

    Article  PubMed  CAS  Google Scholar 

  10. Rexrode KM, Carey VJ, Hennekens CH, et al. Abdominal adiposity and coronary heart disease in women. JAMA 1998, 280: 1843–8.

    Article  PubMed  CAS  Google Scholar 

  11. Vigano A, Mora S, Testolin C, et al. Increased lipodystrophy is associated with increased exposure to highly active antiretroviral therapy in HIV-infected children. J Acquir Immune Defic Syndr 2003, 32: 482–9.

    Article  PubMed  Google Scholar 

  12. Graber AL. Syndrome of lipodystrophy, hyperlipidemia, insulin resistance, and diabetes in treated patients with human immunodeficiency virus infection. Endocr Pract 2001, 7: 430–7.

    Article  PubMed  CAS  Google Scholar 

  13. Pontiroli AE, Pizzocri P, Giacomelli M, et al. Ultrasound measurement of visceral and subcutaneous fat in morbidly obese patients before and after laparoscopic adjustable gastric banding: comparison with computerized tomography and with anthropometric measurements. Obes Surg 2002, 12: 648–51.

    Article  PubMed  CAS  Google Scholar 

  14. Armellini F, Zamboni M, Harris T, Micciolo R, Bosello O. Sagittal diameter minus subcutaneous thickness. An easy-to-obtain parameter that improves visceral fat prediction. Obes Res 1997, 5: 315–20.

    CAS  Google Scholar 

  15. Zamboni M, Turcato E, Armellini F, et al. Sagittal abdominal diameter as a practical predictor of visceral fat. Int J Obes Relat Metab Disord 1998, 22: 655–60.

    Article  PubMed  CAS  Google Scholar 

  16. Mynarcik DC, McNurlan MA, Steigbigel RT, Fuhrer J, Gelato MC. Association of severe insulin resistance with both loss of limb fat and elevated serum tumor necrosis factor receptor levels in HIV lipodystrophy. J Acquir Immune Defic Syndr 2000, 25: 312–21.

    Article  PubMed  CAS  Google Scholar 

  17. Steppan CM, Lazar MA. The current biology of resistin. J Intern Med 2004, 255: 439–47.

    Article  PubMed  CAS  Google Scholar 

  18. Hadigan C, Yawetz S, Thomas A, Havers F, Sax PE, Grinspoon S. Metabolic effects of rosiglitazone in HIV lipodystrophy: a randomized controlled trial. Ann Intern Med 2004, 140: 786–94.

    Article  PubMed  CAS  Google Scholar 

  19. Barb D, Wadhwa SG, Kratzsch J, et al. Circulating resistin levels are not associated with fat redistribution, insulin resistance, or metabolic profile in patients with the highly active antiretroviral therapy-induced metabolic syndrome. J Clin Endocrinol Metab 2005, 90: 5324–8.

    Article  PubMed  CAS  Google Scholar 

  20. Kamin D, Hadigan C, Lehrke M, Mazza S, Lazar MA, Grinspoon S. Resistin levels in human immunodeficiency virus-infected patients with lipoatrophy decrease in response to rosiglitazone. J Clin Endocrinol Metab 2005, 90: 3423–6.

    Article  PubMed  CAS  Google Scholar 

  21. Youn BS, Yu KY, Park HJ, et al. Plasma resistin concentrations measured by ELISA using a newly developed monoclonal antibody are elevated in individuals with type 2 diabetes mellitus. J Clin Endocrinol Metab 2004, 89: 150–6.

    Article  PubMed  CAS  Google Scholar 

  22. Fujinami A, Obayashi H, Ohta K, et al. Enzymelinked immunosorbent assay for circulating human resistin: resistin concentrations in normal subjects and patients with type 2 diabetes. Clin Chim Acta 2004, 339: 57–63.

    Article  PubMed  CAS  Google Scholar 

  23. Volarova de Courten B, Degawa-Yamauchi M, Considine RV, Tataranni PA. High serum resistin is associated with an increase in adiposity but not a worsening of insulin resistance in Pima Indians. Diabetes 2004, 53: 1279–84.

    Article  Google Scholar 

  24. Lee JH, Chan JL, Yiannakouris N, et al. Circulating resistin levels are not associated with obesity or insulin resistance in humans and are not regulated by fasting or leptin administration: cross-sectional and interventional studies in normal, insulin-resistant, and diabetic subjects. J Clin Endocrinol Metab 2003, 88: 4848–56.

    Article  PubMed  CAS  Google Scholar 

  25. Moon B, Kwan JJ, Duddy N, Sweeney G, Begum N. Resistin inhibits glucose uptake in L6 cells independently of changes in insulin signaling and GLUT4 translocation. Am J Physiol Endocrinol Metab 2003, 285: E106–15.

    PubMed  CAS  Google Scholar 

  26. Rajala MW, Obici S, Scherer PE, Rossetti L. Adipose-derived resistin and gut-derived resistin-like molecule-β selectively impair insulin action on glucose production. J Clin Invest 2003, 111: 225–30.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Fain JN, Cheema PS, Bahouth SW, Lloyd Hiler M. Resistin release by human adipose tissue explants in primary culture. Biochem Biophys Res Commun 2003, 300: 674–8.

    Article  PubMed  CAS  Google Scholar 

  28. Savage DB, Sewter CP, Klenk ES, et al. Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor — action in humans. Diabetes 2001, 50: 2199–202.

    Article  PubMed  CAS  Google Scholar 

  29. Kaser S, Kaser A, Sandhofer A, Ebenbichler CF, Tilg H, Patsch JR. Resistin messenger — RNA expression is increased by proinflammatory cytokines in vitro. Biochem Biophys Res Commun 2003, 309: 286–90.

    Article  PubMed  CAS  Google Scholar 

  30. Patel L, Buckels AC, Kinghorn IJ, et al. Resistin is expressed in human macrophages and directly regulated by PPAR activators. Biochem Biophys Res Commun 2003, 300: 472–6.

    Article  PubMed  CAS  Google Scholar 

  31. Cacciari E, Milani S, Balsamo A, Dammacco F, De Luca F, Chiarelli F. Italian cross-sectional growth charts for height, weight and BMI (6–20 y). Eur J Clin Nutr 2002, 56: 171–80.

    Article  PubMed  CAS  Google Scholar 

  32. European Paediatric Lipopdystrophy Group. Anteretroviral therapy, fat redistribution and hyperlipidemia in HIV-infected children in Europe. AIDS 2004, 18: 1443–51.

    Article  Google Scholar 

  33. Snijder MB, Visser M, Dekker JM, et al. The prediction of visceral fat by dual-energy X-ray absorptiometry in the elderly: a comparison with computed tomography and anthropometry. Int J Obes Relat Metab Disord 2002, 26: 984–93.

    Article  PubMed  CAS  Google Scholar 

  34. Hickman TB, Briefel RR, Carroll MD, et al. Distributions and trends of serum lipid levels among United States children and adolescents ages 4–19 years: data from the Third National Health and Nutrition Examination Survey. Prev Med 1998, 27: 879–90.

    Article  PubMed  CAS  Google Scholar 

  35. Laron Z, Huerter P, Weber B. Standardization of oral glucose tolerance test. Acta Paediatr Belg 1977, 30: 124–5.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, University Federico II, Via S. Pansini 5, 80131, Naples, Italy

    M. I. Spagnuolo MD, PhD, E. Bruzzese, G. De Marco, A. Officioso, M. Volpicelli, R. Iorio, A. Franzese & A. Guarino

  2. Department of Biomorphological and Functional Sciences, Federico II University, Italy

    G. F. Vallone & N. Fasano

  3. School of Movement Sciences, Parthenope University, Naples, Italy

    G. Valerio

Authors
  1. M. I. Spagnuolo MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Bruzzese
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. F. Vallone
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. Fasano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. De Marco
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Officioso
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G. Valerio
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Volpicelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. R. Iorio
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A. Franzese
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. A. Guarino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. I. Spagnuolo MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spagnuolo, M.I., Bruzzese, E., Vallone, G.F. et al. Is resistin a link between highly active antiretroviral therapy and fat redistribution in HIV-infected children?. J Endocrinol Invest 31, 592–596 (2008). https://doi.org/10.1007/BF03345607

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03345607

Key-words

Search

Navigation