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Elevated ratio of acylated to unacylated ghrelin in children and young adults with Prader-Willi syndrome.

Abstract
Prader-Willi syndrome (PWS) is characterized by a switch from failure to thrive to excessive weight gain and hyperphagia in early childhood. Hyperghrelinemia may be involved in the underlying mechanisms of the switch. The purpose of this study is to evaluate acylated ghrelin (AG) and unacylated ghrelin (UAG) levels in PWS and investigate their associations with hyperphagia. This is a cross-sectional clinical study conducted in three PWS expert centers in the Netherlands and France. Levels of AG and UAG and the AG/UAG ratio were determined in 138 patients with PWS (0.2-29.4 years) and compared with 50 age-matched obese subjects (4.3-16.9 years) and 39 healthy controls (0.8-28.6 years). AEBSF was used to inhibit deacylation of AG. As a group, PWS patients had higher AG but similar UAG levels as healthy controls (AG 129.1 vs 82.4 pg/ml, p = 0.016; UAG 135.3 vs 157.3 pg/ml, resp.), resulting in a significantly higher AG/UAG ratio (1.00 vs 0.61, p = 0.001, resp.). Obese subjects had significantly lower AG and UAG levels than PWS and controls (40.3 and 35.3 pg/ml, resp.), but also a high AG/UAG ratio (1.16). The reason for the higher AG/UAG ratio in PWS and obese was, however, completely different, as PWS had a high AG and obese a very low UAG. PWS patients without weight gain or hyperphagia had a similar AG/UAG ratio as age-matched controls, in contrast to those with weight gain and/or hyperphagia who had an elevated AG/UAG ratio. The switch to excessive weight gain in PWS seems to coincide with an increase in the AG/UAG ratio, even prior to the start of hyperphagia.
AuthorsR J Kuppens, G Diène, N E Bakker, C Molinas, S Faye, M Nicolino, D Bernoux, P J D Delhanty, A J van der Lely, S Allas, M Julien, T Delale, M Tauber, A C S Hokken-Koelega
JournalEndocrine (Endocrine) Vol. 50 Issue 3 Pg. 633-42 (Dec 2015) ISSN: 1559-0100 [Electronic] United States
PMID25989955 (Publication Type: Journal Article)
Chemical References
  • Ghrelin
  • IGF1 protein, human
  • Insulin-Like Growth Factor I
Topics
  • Acylation
  • Adolescent
  • Age Factors
  • Body Mass Index
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Eating
  • Feeding Behavior
  • Female
  • Genotype
  • Ghrelin (blood)
  • Humans
  • Hyperphagia (blood)
  • Insulin-Like Growth Factor I (metabolism)
  • Male
  • Obesity (blood)
  • Prader-Willi Syndrome (blood)

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