Lack of Postprandial Peak in Brain-Derived Neurotrophic Factor in Adults with Prader-Willi Syndrome

Abstract

Context: Prader-Willi syndrome (PWS) is characterized by severe hyperphagia. Brain-derived neurotrophic factor (BDNF) and leptin are reciprocally involved in energy homeostasis. Objectives: To analyze the role of BDNF and leptin in satiety in genetic subtypes of PWS. Design: Experimental study. Setting: University hospital. Subjects: 90 adults: 30 PWS patients; 30 age-sex-BMI-matched obese controls; and 30 age-sex-matched lean controls. Interventions: Subjects ingested a liquid meal after fasting ≥10 hours. Main Outcome Measures: Leptin and BDNF levels in plasma extracted before ingestion and 30’, 60’, and 120’ after ingestion. Hunger, measured on a 100-point visual analogue scale before ingestion and 60’ and 120’ after ingestion. Results: Fasting BDNF levels were lower in PWS than in controls (p = 0.05). Postprandially, PWS patients showed only a truncated early peak in BDNF, and their BDNF levels at 60' and 120' were lower compared with lean controls (p<0.05). Leptin was higher in PWS patients than in controls at all time points (p<0.001). PWS patients were hungrier than controls before and after eating. The probability of being hungry was associated with baseline BDNF levels: every 50-unit increment in BDNF decreased the odds of being hungry by 22% (OR: 0.78, 95%CI: 0.65–0.94). In uniparental disomy, the odds of being hungry decreased by 66% (OR: 0.34, 90%CI: 0.13–0.9). Postprandial leptin patterns did no differ among genetic subtypes. Conclusions: Low baseline BDNF levels and lack of postprandial peak may contribute to persistent hunger after meals. Uniparental disomy is the genetic subtype of PWS least affected by these factors.

This project was supported by a grant from Fondo de Investigacio´n Sanitaria del Instituto Carlos III (PI-14/02057), and by two grants from Fundacio´ Parc Taulı´(CIR 2010/006 and CIR 2011/ 004), all to AC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.