Higher Ghrelin/PYY Ratio Noted in Prader-Willi Syndrome

Girl looking in refrigerator
Girl looking in refrigerator
Ghrelin to peptide YY ratio may be novel marker for orexigenic drive.

Orexigenic drive appears to be higher during fasting and mixed meals in children with Prader-Willi syndrome, researchers reported in the Journal of Clinical Endocrinology & Metabolism.

“Food intake is controlled by, and regulates the expression of, orexigenic (ghrelin) and anorexigenic (leptin, insulin, GLP-1, and PPY) hormones produced by white adipose tissue, pancreas, and the gastrointestinal (GI) tract. However, the roles of specific macronutrients in the regulation of orexigens and anorexigens are poorly understood,” they wrote.

Children with obesity and Prader-Willi syndrome offer a unique model for studying the macronutrient regulation of orexigenic and anorexigenic hormones, according to the researchers. Therefore, they opted to study the relationship between ghrelin levels and insulin, plasma glucose and PPY, as well as the effects of long-term GH therapy, in this patient population.

For the randomized, crossover study, the researchers compared the effects of high-carbohydrate and high-fat meals and GH therapy in 14 children with Prader-Willi syndrome vs. 14 BMI-matched controls. Participants received isocaloric breakfast meals, either high-carbohydrate or high-fat, on separate days.

Results revealed lower fasting insulin and higher fasting ghrelin as well as a higher ghrelin/PPY ratio in children with Prader-Willi syndrome, as compared with the BMI-matched controls, at all postprandial time points (P<.0001).

In terms of ghrelin suppression in the children with Prader-Willi syndrome, carbohydrates were more effective than fat (P=.028). In the BMI-matched controls, high-carbohydrate and high-fat meals were comparable. However, they were less potent in Prader-Willi syndrome (P=.011).

After high-fat meals, the increase in PYY was attenuated in Prader-Willi syndrome (P=.037), and consequently, the postprandial ghrelin/PYY ratio stayed higher throughout.

Data also indicated less of an increase in insulin and less of a decrease in ghrelin among children with Prader-Willi syndrome who were treated with GH vs. untreated children, while PYY responses were similar.

In light of these findings, the researchers concluded that children with Prader-Willi syndrome have a higher orexigenic drive under fasting conditions as well as during a mixed meal tolerance test. They also noted that the ghrelin/PYY ratio may be a marker of or stimulus for the development of hyperphagia in these children.

“Therapeutic approaches designed to increase PYY and/or reduce ghrelin production or action might therefore prove beneficial in children with [Prader-Willi syndrome],” the researchers wrote.

“Longer-term randomized controlled trials of varying macronutrient composition will facilitate the development of dietary therapies that attenuate hyperphagia, prevent weight gain, and promote weight loss.”


  1. Balikcioglu PG et al. J Clin Endocrinol Metab. 2015;doi:10.1210/jc.2015-2503.