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

Eur J Pediatr. 2009 Sep;168(9):1043-8. doi: 10.1007/s00431-008-0876-x. Epub 2008 Nov 29.

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.

MeSH terms

  • Adolescent
  • Astrocytoma / metabolism
  • Astrocytoma / pathology
  • Astrocytoma / physiopathology
  • Body Mass Index
  • Child
  • Craniopharyngioma / metabolism
  • Craniopharyngioma / pathology
  • Craniopharyngioma / physiopathology
  • Dysgerminoma / metabolism
  • Dysgerminoma / pathology
  • Dysgerminoma / physiopathology
  • Female
  • Glucose Tolerance Test
  • Glycemic Index
  • Homeostasis / physiology
  • Humans
  • Hypothalamic Neoplasms / metabolism
  • Hypothalamic Neoplasms / pathology
  • Hypothalamic Neoplasms / physiopathology
  • Hypothalamus / metabolism*
  • Hypothalamus / pathology
  • Hypothalamus / physiopathology*
  • Insulin / blood
  • Insulin / physiology*
  • Leptin / blood
  • Leptin / physiology*
  • Male
  • Obesity / metabolism*
  • Obesity / physiopathology*
  • Receptors, Leptin / physiology*
  • Resistin / blood
  • Resistin / physiology*

Substances

  • Insulin
  • LEPR protein, human
  • Leptin
  • RETN protein, human
  • Receptors, Leptin
  • Resistin