title: Hyperleptinaemia rather than fasting hyperinsulinaemia is associated with obesity following hypothalamic damage in children.
abstract: BACKGROUND
  Obesity following hypothalamic damage is often severe and resistant to lifestyle changes. Disruption of hypothalamic feedback mechanisms that maintain energy homeostasis may be responsible for this intractable obesity. Adipocytokines including insulin and leptin are also known to be important regulators of appetite and weight.
  
  
  OBJECTIVE
  To investigate the role of insulin, leptin, adiponectin and resistin in the aetiology of hypothalamic obesity (HO).
  
  
  METHODS
  This was a cross-sectional study of three groups of children, those with HO, congenital hypopituitarism (CH) and simple obesity (SO).
  
  
  RESULTS
  A total of 69 children (HO=28, CH=18, SO=23) had leptin, resistin, adiponectin and insulin measured. Although fasting hyperinsulinaemia and insulin resistance were demonstrated, no differences in insulin or insulin resistance were seen between the groups. The HO group, however, had higher levels of leptin, adiponectin and resistin, which persisted even after adjusting for fat mass, compared with the other groups (P<0.05).
  
  
  CONCLUSIONS
  No differences in fasting hyperinsulinaemia or insulin resistance were seen between the groups; however, leptin levels are elevated, even after adjusting for fat mass, suggesting that an element of leptin resistance is associated with HO. This is consistent with the inability of leptin to act on the hypothalamus, either due to transport across the blood-brain barrier or dysfunctional receptors. The lack of response to leptin may be more important in the development of obesity in these individuals, and the fasting hyperinsulinaemia is a result of the increased adipose tissue rather than the cause of the weight gain.
authors.affiliation: Department of Endocrinology, Birmingham Children's Hospital, Birmingham, B4 6NH, UK. guftar.shaikh@nhs.net
authors.forename: M Guftar
authors.initials: MG
authors.lastname: Shaikh
authors.forename: Richard G
authors.initials: RG
authors.lastname: Grundy
authors.forename: Jeremy M W
authors.initials: JM
authors.lastname: Kirk
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005215:Fasting / Q000097:blood*; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood* / Q000150:complications; D007018:Hypopituitarism / Q000097:blood / Q000150:complications; D007027:Hypothalamic Diseases / Q000097:blood* / Q000150:complications; D007031:Hypothalamus / Q000378:metabolism / Q000473:pathology; D020738:Leptin / Q000097:blood*; D008297:Male; D009765:Obesity / Q000097:blood* / Q000150:complications
chemical_list: D020738:Leptin