The Impact of Dietary Protein on Appetite-Regulating Hormones and Energy Metabolism in Children with Prader-Willi Syndrome

• Author / Creator

  Alsaif, Maha

• Prader-Willi syndrome (PWS) is a unique model of childhood obesity characterized by disordered satiety. The excessive weight gain caused by an imbalance between energy intake and expenditure associated with PWS is of concern to healthcare professionals and caregivers who acknowledge that weight management is an essential but challenging aspect of care for these children. To improve the effectiveness of treatments to curb the development of obesity in PWS, a more comprehensive understanding of the underlying mechanisms associated with altered energy balance in these children is needed. Therefore, the overall objective of this research was (1) to determine the impact of food intake (FI), higher protein (HP) meals and standard meals (SM) on postprandial regulation of ghrelin and asprosin; (2) other satiety factor concentrations; and (3) energy balance in children with PWS.
  In study 1, two test meals were compared to a SM meal in 10 children with PWS and 7 body mass index (BMI) z-score matched children in a randomized, crossover study design. The first test meal had a higher protein–lower carbohydrate (HP-LC) content and the second test meal had a higher protein–lower fat (HP-LF) content. Under fasting conditions, the PWS group had higher concentrations of both acyl ghrelin (AG) (p = 0.02) and desacyl ghrelin (DAG) than controls, but a comparable ratio of AG:DAG. AG and DAG were reduced in both groups following all meals, but concentrations of AG and DAG remained higher in PWS across all postprandial time points (p = 0.002 and p < 0.001, respectively). Glucagon-like peptide 1 (GLP-1) concentrations were higher after the HP-LC meal than the SM at 2 and 4 hours (p = 0.027 and p = 0.044, respectively) and at hour 4 (p = 0.02) following the HP-LF in the PWS group only; peptide tyrosine tyrosine (PYY) responses were comparable.
  In study 2, fasting and 1 hour post-meal serum concentrations of asprosin were measured in 52 children, 23 with PWS, 8 with obesity, and 21 healthy weights. The decrease in serum asprosin relative to baseline was not different between children with PWS and BMI-z score matched children. In children with PWS, fasting asprosin was positively correlated with AG and 1-hour postprandial asprosin was negatively correlated with insulin. Additionally, fasting asprosin was negatively correlated with age and insulin in children with obesity and with age in healthy weight children. After adjusting for age, sex and BMI z-score, asprosin showed a positive correlation with glucose in children with obesity but not in children with PWS or healthy weight children. In study 3, in a randomized, crossover study design, 5 youth with PWS were randomly allocated to two isocaloric arms: a) standard diet (SD); b) high-protein (HP) diet. Participants received the prescribed diets (three meals plus two snacks per day accompanied by either a powder supplement (HP) or an extra snack (SD) for one day prior to each study visit and a breakfast meal inside a whole-body calorimetry unit (WBCU). Resting energy expenditure (REE), postprandial energy expenditure (PEE) and respiratory exchange ratio (RER) were assessed. PEE calculated as “fixed REE” was higher after the HP meal compared to SM. A lower RER was observed after the HP diet in comparison to the SD (0.80 ± 0.2 vs 0.86 ± 0.2; p < 0.009). However, no significant difference in subjective appetite assessment between the HP meal and the SM was found.
  The major findings of this research were that higher concentrations of total ghrelin in children with PWS were due to higher concentrations in both AG and DAG, with no change in the AG:DAG ratio. Meal consumption also suppressed both forms of ghrelin to a greater extent in children with PWS. Higher protein meals stimulated greater increases in GLP-1 and PYY in PWS children compared to controls. RER after the HP diet was significantly lower compared to SD. In addition, this research highlights the heterogeneity in PEE in youth with PWS in response to HP diet and will contribute to the conceptualization of further research exploring PEE; considering, sex, puberty statues and body composition factors that influence response to energy metabolism in children with and without PWS.

• Subjects / Keywords

  • Prader-Willi Syndrome

• Graduation date

  Spring 2020

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-ytrz-qw97

• License

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