Macronutrient regulation of ghrelin and peptide YY in pediatric obesity and prader-willi syndrome

Background: The roles of macronutrients and GH in the regulation of food intake in pediatric obesity and Prader-Willi Syndrome (PWS) are poorly understood. Objective:Wecompared effects of high-carbohydrate (HC) and high-fat (HF) meals andGHtherapy on ghrelin, insulin, peptide YY (PYY), and insulin sensitivity in children with PWS and body mass index (BMI)-matched obese controls (OCs). Methods: In a randomized, crossover study, 14 PWS (median, 11.35 y; BMI z score [BMI-z], 2.15) and 14 OCs (median, 11.97 y; BMI-z, 2.35) received isocaloric breakfast meals (HC or HF) on separate days. Blood samples were drawn at baseline and every 30 minutes for 4 hours. Mixed linear models were adjusted for age, sex, and BMI-z. Results: Relative to OCs, children withPWShad lower fasting insulin and higher fasting ghrelin and ghrelin/PYY. Ghrelin levels were higher in PWS across all postprandial time points (P = .0001). Carbohydrate was more potent than fat in suppressing ghrelin levels in PWS (P < .028); HC and HF were equipotent in OCs but less potent than in PWS (P < .011). The increase in PYY following HF was attenuated in PWS (P < .037); thus, postprandial ghrelin/PYY remained higher throughout. A lesser increase in insulin and lesser decrease in ghrelin were observed in GH-treated PWS patients than in untreated patients; PYY responses were comparable. Conclusion: Children withPWShave fastingandpostprandial hyperghrelinemiaandanattenuated PYY response to fat, yielding a high ghrelin/PYY ratio. GH therapy in PWS is associated with increased insulin sensitivity and lesser postprandial suppression of ghrelin. The ratio Ghrelin/PYY may be a novel marker of orexigenic drive.