Macronutrient regulation of Ghrelin and Peptide YY in Pediatric Obesity and Prader Willi Syndrome (PWS)


Balikcioglu PG, Balikcioglu M, Muehlbauer MJ, Purnell JQ, Broadhurst D, Freemark M, Haqq AM

Scientific Notation:

J Clin Endocrinol Metab. 2015 Aug 10:jc20152503. [Epub ahead of print]

Publication Link:




The roles of macronutrients and GH in the regulation of food intake in pediatric obesity and PWS are poorly understood.


We compared effects of high carbohydrate (HC) and high fat (HF) meals and GH therapy on ghrelin, insulin, PYY, and insulin sensitivity in children with PWS and BMI-matched obese controls (OC).


In a randomized, cross-over study, 14 PWS (median 11.35 yr; BMI-z 2.15) and 14 OC (median 11.97 yr; BMI-z 2.35) received iso-caloric breakfast meals (HC or HF) on separate days. Blood samples were drawn at baseline and q30 min for 4 hr. Mixed linear models were adjusted for age, sex, and BMI-z.


Relative to OC, PWS children had lower fasting insulin and higher fasting ghrelin and ghrelin/PYY. Ghrelin levels were higher in PWSacross all postprandial time points (p<0.0001). Carbohydrate was more potent than fat in suppressing ghrelin levels in PWS (p=0.028); HC and HF were equipotent in OC but less potent than in PWS (p=0.011). The rise in PYY following HF was attenuated in PWS (p=0.037); thus postprandialghrelin/PYY remained higher throughout. A lesser rise in insulin and lesser fall in ghrelin were observed in GH-treated PWS patients than in untreated patients; PYY responses were comparable.


Children with PWS have fasting and postprandial hyperghrelinemia and an attenuated PYY response to fat, yielding a highghrelin/PYY ratio. GH therapy in PWS is associated with increased insulin sensitivity and lesser postprandial suppression of ghrelin. The ratioGhrelin/PYY may be a novel marker of orexigenic drive.

PMID: 26259133 [PubMed - as supplied by publisher]