Advertisement

European Journal of Pediatrics

, Volume 168, Issue 9, pp 1043–1048 | Cite as

The role of leptin, soluble leptin receptor, resistin, and insulin secretory dynamics in the pathogenesis of hypothalamic obesity in children

  • Tulay Guran
  • Serap Turan
  • Abdullah BereketEmail author
  • Teoman Akcay
  • Goksenin Unluguzel
  • Firdevs Bas
  • Hulya Gunoz
  • Nurcin Saka
  • Ruveyde Bundak
  • Feyza Darendeliler
  • Pinar Isguven
  • Metin Yildiz
  • Erdal Adal
  • Sevil Sarikaya
  • Leyla Akin Baygin
  • Nihal Memioglu
  • Hasan Onal
  • Oya Ercan
  • Goncagul Haklar
Original Paper

Abstract

Introduction

In this study, we have investigated the role of leptin, soluble leptin receptor(sOb-R), resistin, and insulin secretory dynamics in the development of hypothalamic obesity.

Materials and methods

Children who had hypothalamo-pituitary tumor were divided into two groups. First group included obese-overweight (hypothalamic obese = HOB group, n = 23) and second group included non-obese children (hypothalamic non-obese = HNOB group, n = 16). Exogenously obese-overweight children (OB group, n = 22) were included as controls. Basal and second-hour serum glucose and insulin in oral glucose tolerance test (OGTT), basal serum leptin, sOb-R, resistin levels, and homeostasis model assessment (HOMA) indexes were compared between the groups.

Results

Age, sex, and pubertal status were similar in study groups. Median and interquartile ranges of body mass index (BMI) z scores were similar in HOB and OB groups (2.0 (1.5–2.1) and 2.1 (1.8–2.3), respectively). Serum leptin levels corrected for BMI were highest and total leptin/sOb-R ratios (free leptin index (FLI)) tended to be higher in HOB than HNOB and OB groups, indicating leptin resistance (leptin/BMI, 4.0 (1.6–5.2), 1.5 (0.8–3.1), and 2.5 (1.8–3.5); FLI, 2.0 (0.8–3.5), 0.6 (0.3–1.2), and 1.5 (1–2.3) in HOB, HNOB, and OB groups; respectively). Serum resistin levels were similar in groups (2.6 (1.9–3.1), 2.8 (1.7–3.4), and 3.0 (2.2–3.5) ng/ml in HOB, HNOB, and OB groups, respectively). Basal serum glucose, basal and second-hour insulin levels in OGTT, and HOMA index were higher in OB group than the HOB and HNOB groups, indicating insulin resistance in simple obesity; however, increment of insulin to same glycemic load in OGTT was highest in the HOB group indicating insulin dysregulation (p < 0.05).

Conclusion

Hypothalamic obesity seems to be related to both dysregulated afferent (leptin) and efferent (insulin) neural outputs through the autonomic nervous system resulting in energy storage as fat.

Keywords

Hypothalamic obesity Leptin Soluble insulin receptor Resistin Insulin 

Abbreviations

sOb-R

soluble leptin receptor

HOB

Hypothalamic obese

HNOB

Hypothalamic non-obese

OB

Obese

OGTT

Oral glucose tolerance test

BMI

Body mass index

FLI

Free leptin index

HOMA-IR

Homeostasis model assessment for insulin resistance index

Notes

Acknowledgment

The authors would like to thank pediatric dietician Sabiha Keskin for caloric analyses of the children and SERONO Company who provided the commercial kits for serum leptin, soluble leptin receptor, and resistin.

References

  1. 1.
    Ainsworth BE, Haskell WL, Leon AS (1993) Compendium of physical activities: classification of energy costs of human physical activities. Med Sci Sports Exerc 25(1):71–80PubMedCrossRefGoogle Scholar
  2. 2.
    American Diabetes Association (2000) Type 2 diabetes in children (consensus statement). Diabetes Care 23(3):381–389CrossRefGoogle Scholar
  3. 3.
    Anderlová K, Kremen J, Dolezalová R (2006) The influence of very-low-calorie-diet on serum leptin, soluble leptin receptor, adiponectin and resistin levels in obese women. Physiol Res 55(3):277–283PubMedGoogle Scholar
  4. 4.
    Banerjee RR, Rangwala SM, Shapiro JS (2004) Regulation of fasted blood glucose by resistin. Science 303:1195–1198PubMedCrossRefGoogle Scholar
  5. 5.
    Bray GA, York DA (1979) Hypothalamic and genetic obesity in experimental animals: an autonomic and endocrine hypothesis. Physiol Rev 59(3):719–809PubMedGoogle Scholar
  6. 6.
    Chanchay S, Tungtrongchitr R, Harnroongroj T (2006) Plasma resistin, insulin concentration in non-diabetic and diabetic, overweight/obese Thai. Int J Vitam Nutr Res 76(3):125–131PubMedCrossRefGoogle Scholar
  7. 7.
    Cole TJ, Bellizzi MC, Flegal KM, Dietz WH (2000) Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320(7244):1240–1243PubMedCrossRefGoogle Scholar
  8. 8.
    Housová J, Anderlová K, Křížová J (2004) Serum adiponectin and resistin concentrations in patients with restrictive and binge/purge form of anorexia nervosa and bulimia nervosa. J Clin Endocrinol Metab 90:1366–1370PubMedCrossRefGoogle Scholar
  9. 9.
    Igaki N, Tanaka M, Goto T (2005) Markedly improved glycemic control and enhanced insulin sensitivity in a patient with type 2 diabetes complicated by a suprasellar tumor treated with pioglitazone and metformin. Intern Med 44(8):832–837PubMedCrossRefGoogle Scholar
  10. 10.
    Iqbal N, Seshadri P, Stern L (2005) Serum resistin is not associated with obesity or insulin resistance in humans. Eur Rev Med Pharmacol Sci 9(3):161–165PubMedGoogle Scholar
  11. 11.
    Lammert A, Kiess W, Bottner A (2001) Soluble leptin receptor presents the main leptin binding activity in human blood. Biochem Biophys Res Commun 283:982–988PubMedCrossRefGoogle Scholar
  12. 12.
    Lehrke M, Reilly MP, Millington SC (2004) An inflammatory cascade leading to hyperresistinemia in humans. PLoS Med 1:e45PubMedCrossRefGoogle Scholar
  13. 13.
    Lustig RH (2006) Childhood obesity: behavioral aberration or biochemical drive? Reinterpreting the first law of thermodynamics. Nat Clin Pract Endocrinol Metab 2(8):447–458PubMedCrossRefGoogle Scholar
  14. 14.
    Lustig RH, Hinds PS, Ringwald-Smith K (2003) Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial. J Clin Endocrinol Metab 88(6):2586–2592PubMedCrossRefGoogle Scholar
  15. 15.
    Lustig RH, Rose SR, Burghen GA (1999) Hypothalamic obesity caused by cranial insult in children: altered glucose and insulin dynamics and reversal by a somatostatin agonist. J Pediatr 135(2 Pt 1):162–168PubMedGoogle Scholar
  16. 16.
    McTernan PG, McTernan CL, Chetty R (2002) Increased resistin gene and protein expression in human abdominal adipose tissue. J Clin Endocrinol Metab 87:2407PubMedCrossRefGoogle Scholar
  17. 17.
    Muse ED, Lam TK, Scherer PE, Rossetti L (2007) Hypothalamic resistin induces hepatic insulin resistance. J Clin Invest 117(6):1670–1678PubMedCrossRefGoogle Scholar
  18. 18.
    Müller HL, Müller-Stöver S, Gebhardt U (2006) Secondary narcolepsy may be a causative factor of increased daytime sleepiness in obese childhood craniopharyngioma patients. J Pediatr Endocrinol Metab 19(Suppl 1):423–429PubMedGoogle Scholar
  19. 19.
    Pastucha D, Malincíková J, Hyjánek J (2007) Obesity and insulin resistance in childhood. Cent Eur J Public Health 15(3):103–105PubMedGoogle Scholar
  20. 20.
    Patel L, Cooper CD, Quinton ND, Butler GE, Gill MS, Jefferson IG, Kibirige MS, Price DA, Shalet SM, Wales JK, Ross RJ, Clayton PE, Northern Paediatric Endocrine Group, UK (2002) Serum leptin and leptin binding activity in children and adolescents with hypothalamic dysfunction. J Pediatr Endocrinol Metab 15(7):963–971PubMedGoogle Scholar
  21. 21.
    Proto C, Romualdi D, Cento RM (2007) Free and total leptin serum levels and soluble leptin receptors levels in two models of genetic obesity: the Prader Willi and the Down syndromes. Metabolism 56(8):1076–1080PubMedCrossRefGoogle Scholar
  22. 22.
    Rangwala SM, Rich AS, Rhoades B (2004) Abnormal glucose homeostasis due to chronic hyperresistinemia. Diabetes 53(8):1937–1941PubMedCrossRefGoogle Scholar
  23. 23.
    Reinehr T, Kratzsch J, Kiess W, Andler W (2005) Circulating soluble leptin receptor, leptin, and insulin resistance before and after weight loss in obese children. Int J Obes (Lond) 29(10):1230–1235CrossRefGoogle Scholar
  24. 24.
    Rose SR, Schreiber RE, Kearney NS (2004) Hypothalamic dysfunction after chemotherapy. J Pediatr Endocrinol Metab 17(1):55–66PubMedGoogle Scholar
  25. 25.
    Roth C, Wilken B, Hanefeld F (1998) Hyperphagia in children with craniopharyngioma is associated with hyperleptinaemia and a failure in the downregulation of appetite. Eur J Endocrinol 138(1):89–91PubMedCrossRefGoogle Scholar
  26. 26.
    Rutter MM, Rose SR (2007) Long-term endocrine sequelae of childhood cancer. Curr Opin Pediatr 19(4):480–487PubMedCrossRefGoogle Scholar
  27. 27.
    Shaikh MG, Grundy R, Kirk J (2008) Hyperleptinaemia rather than fasting hyperinsulinaemia is associated with obesity following hypothalamic damage in children. Eur J Endocrinol, Sep 26 (in press)Google Scholar
  28. 28.
    Srinivasan S, Ogle GD, Garnett SP (2004) Features of the metabolic syndrome after childhood craniopharyngioma. J Clin Endocrinol Metab 89(1):81–86PubMedCrossRefGoogle Scholar
  29. 29.
    Tiosano D, Eisentein I, Militianu D (2003) 11 beta-hydroxysteroid dehydrogenase activity in hypothalamic obesity. J Clin Endocrinol Metab 88(1):379–384PubMedCrossRefGoogle Scholar
  30. 30.
    Zou CC, Liang L, Hong F (2007) Relationship between insulin resistance and serum levels of adiponectin and resistin with childhood obesity. Indian Pediatr 44(4):275–279PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Tulay Guran
    • 1
  • Serap Turan
    • 1
  • Abdullah Bereket
    • 1
    • 8
    Email author
  • Teoman Akcay
    • 1
  • Goksenin Unluguzel
    • 2
  • Firdevs Bas
    • 3
  • Hulya Gunoz
    • 3
  • Nurcin Saka
    • 3
  • Ruveyde Bundak
    • 3
  • Feyza Darendeliler
    • 3
  • Pinar Isguven
    • 4
  • Metin Yildiz
    • 4
  • Erdal Adal
    • 5
  • Sevil Sarikaya
    • 5
  • Leyla Akin Baygin
    • 5
  • Nihal Memioglu
    • 6
  • Hasan Onal
    • 7
  • Oya Ercan
    • 7
  • Goncagul Haklar
    • 2
  1. 1.Pediatric EndocrinologyMarmara UniversityIstanbulTurkey
  2. 2.Marmara UniversityIstanbulTurkey
  3. 3.Istanbul Medical Faculty, Pediatric EndocrinologyIstanbul UniversityIstanbulTurkey
  4. 4.Pediatric EndocrinologyGoztepe Education and Research HospitalIstanbulTurkey
  5. 5.Pediatric EndocrinologyBakirkoy Maternity and Child HospitalIstanbulTurkey
  6. 6.Pediatric EndocrinologySisli Etfal Education and Research HospitalIstanbulTurkey
  7. 7.Cerrahpasa Medical Faculty, Pediatric EndocrinologyIstanbul UniversityIstanbulTurkey
  8. 8.Marmara Universitesi HastanesiUskudar-IstanbulTurkey

Personalised recommendations