title: Lower brain-derived neurotrophic factor in patients with prader-willi syndrome compared to obese and lean control subjects.
abstract: BACKGROUND
  Brain-derived neurotrophic factor (BDNF) haploinsufficiency is associated with hyperphagia and obesity in both animals and humans. BDNF appears to function downstream of the leptin-melanocortin signaling pathway to control energy balance. The potential role of BDNF in the etiology of the severe hyperphagia associated with PWS has not been previously explored.
  
  
  OBJECTIVE
  The aim was to compare BDNF concentrations in subjects with PWS and obese controls (OC) and lean controls (LC).
  
  
  METHODS
  We conducted a cross-sectional study at an outpatient clinical research center.
  
  
  METHODS
  We studied 13 subjects with PWS [five females and eight males; mean + or - sd: age, 11.0 + or - 4.1 yr; body mass index (BMI)-Z, 2.05 + or - 0.78], 13 OC (eight females, five males; age, 12.3 + or - 2.7 yr; BMI-Z, 2.18 + or - 0.61), and 13 LC (six females, seven males; age, 12.4 + or - 2.6 yr; BMI-Z, -0.57 + or - 0.73).
  
  
  METHODS
  BDNF was measured in serum and plasma by ELISA. Analysis of covariance adjusted for age, sex, and BMI-Z.
  
  
  RESULTS
  All groups were comparable for age (P = 0.50) and sex distribution (P = 0.49). BMI-Z was comparable between PWS and OC (P = 0.89) and lower in LC (P < 0.001). Adjusted serum BDNF was comparable (P = 0.35) in OC (mean + or - sem: 13.5 + or - 1.2 ng/ml) and LC (19.2 + or - 1.3 ng/ml), but lower in PWS (8.3 + or - 1.2 ng/ml; P = 0.01 vs. OC; P = 0.03 vs. LC). Adjusted plasma BDNF in PWS (217 + or - 130 pg/ml) was lower than OC (422 + or - 126 pg/ml; P = 0.02), but statistically comparable with LC (540 + or - 143 pg/ml; P = 0.10).
  
  
  CONCLUSIONS
  Lower BDNF in PWS suggests insufficient central BDNF production because BDNF in peripheral circulation is believed to reflect cerebral BDNF output. Decreased BDNF may be a potential cause for the disordered satiety and morbid obesity associated with PWS. Further studies are needed to confirm this preliminary pilot study in a larger cohort of patients with PWS.
authors.affiliation: Unit on Growth and Obesity, Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Joan C
authors.initials: JC
authors.lastname: Han
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Muehlbauer
authors.forename: Huaxia N
authors.initials: HN
authors.lastname: Cui
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Haqq
mesh_terms: D000704:Analysis of Variance; D001786:Blood Glucose; D015992:Body Mass Index; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood*; D011218:Prader-Willi Syndrome / Q000097:blood*
chemical_list: D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D007328:Insulin; D020738:Leptin