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The autonomic nervous system (ANS) may play a role in the distribution of body fat and the development of obesity and its complications. Features of individuals with Prader–Willi syndrome (PWS) impacted by PWS molecular genetic classes suggest alterations in ANS function; however, these have been rarely studied and presented with conflicting results. The aim of this study was to investigate if the ANS function is altered in PWS. In this case-control study, we assessed ANS function in 20 subjects with PWS (6 males/14 females; median age 10.5 years) and 27 body mass index (BMI) z-score-matched controls (19 males/8 females; median age 12.8 years). Standardized non-invasive measures of cardiac baroreflex function, heart rate, blood pressure, heart rate variability, quantitative sudomotor axon reflex tests, and a symptom questionnaire were completed. The increase in heart rate in response to head-up tilt testing was blunted (p < 0.01) in PWS compared to controls. Besides a lower heart rate ratio with Valsalva in PWS (p < 0.01), no significant differences were observed in other measures of cardiac function or sweat production. Findings suggest possible altered sympathetic function in PWS. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the feasibility of measuring a postprandial increase in energy expenditure (ΔEE) using a state-of-the-art whole-body calorimetry unit (WBCU) in children and youth with Prader-Willi syndrome (PWS). Five participants (aged 10–25 y) received both a standard and a high-protein diet in a random order (crossover design). Resting energy expenditure, postprandial ΔEE 6 h after intake of a standard [15% of total energy (TE)] and a high-protein (30% TE) meal, and respiratory exchange ratio (RER) were measured in a WBCU. No differences were observed in ΔEE comparing the 2 meals. Mean RER was lower following the high-protein meal (0.80 ± 0.01) compared with the standard meal (0.87 ± 0.02) (P  = 0.009). Despite the high participant burden, it was feasible to conduct this metabolic test in children and youth with PWS. This study paves the way for further studies targeting EE in this patient population. [ABSTRACT FROM AUTHOR]

Summary: In early childhood, individuals with Prader‐Willi syndrome (PWS) experience excess weight gain and severe hyperphagia with food compulsivity, which often leads to early onset morbid obesity. Effective treatments for appetite suppression and weight control are currently unavailable for PWS. Our aim to further understand the pathogenesis of PWS led us to carry out a comprehensive search of the current and emerging therapies for managing hyperphagia and extreme weight gain in PWS. A literature search was performed using PubMed and the following keywords: "PWS" AND "therapy" OR "[drug name]"; reference lists, pharmaceutical websites, and the ClinicalTrials.gov registry were also reviewed. Articles presenting data from current standard treatments in PWS and also clinical trials of pharmacological agents in the pipeline were selected. Current standard treatments include dietary restriction/modifications, exercise, and growth hormone replacement, which appear to have limited efficacy for appetite and weight control in patients with PWS. The long‐term safety and effectiveness of bariatric surgery in PWS remains unknown. However, many promising pharmacotherapies are in development and, if approved, will bring much needed choices into the PWS pharmacological armamentarium. With the progress that is currently being made in our understanding of PWS, an effective treatment may not be far off. [ABSTRACT FROM AUTHOR]

Summary: Objective: Macronutrient regulation of hyperphagia and adiposity in Prader‐Willi syndrome (PWS) is poorly understood. We compared fasting and postprandial concentrations of hormones and metabolites in eight PWS children (age 9‐18 years) fed, in random order, low carbohydrate, high‐fat (LC, 15% carb; 65% fat; 20% protein) and low‐fat, high carbohydrate (LF, 65% carb, 15% fat, 20% protein) diets matched for calories and protein. Methods: Participants were randomized to consume either the LC or LF diet during a first hospital admission and the second diet during a subsequent admission. Blood samples were obtained after overnight fasting and 1 hour after a mixed meal. Results: Relative to subjects consuming the LF diet, subjects consuming the LC diet had: lower postprandial insulin concentrations (P = 0.02); higher fasting GLP‐1 AND GIP concentrations and increased postprandial GLP‐1 (P < 0.02); reduced ratio of fasting ghrelin to GLP‐1 (P = 0.0078); increased FFA and fatty acid oxidation, as assessed by concentrations of even‐chain acylcarnitines (P < 0.001); lower fasting TG and TG/HDL ratio (P < 0.01); and higher concentrations of branch chain amino acids (P < 0.01). There were no changes in glucose, PYY, or adiponectin. CRP, AST and ALT were all higher (P < 0.01) on the LC diet. Conclusions: Increases in GLP‐1 with low carbohydrate feeding and reductions in the ratio of ghrelin to GLP‐1 might limit food intake and improve glycaemic control in PWS. Other potential benefits of carbohydrate restriction may include fat mobilization and oxidation and reductions in the TG/HDL ratio, a marker of insulin resistance. However, increases in CRP, AST and ALT necessitate longer‐term studies of low carbohydrate efficacy and safety. [ABSTRACT FROM AUTHOR]

Dietary management is important to prevent severe obesity in individuals with Prader‐Willi syndrome (PWS); however, few studies have examined dietary intake and quality in youth with PWS. Our objective was to estimate intake of essential nutrients and diet quality in youth with PWS compared to those without PWS. Three‐day food records were used to estimate intake of energy, nutrients, nutrient‐density, foods, and adherence to healthy eating guidelines. Data were presented as medians and interquartile ranges with Mann–Whitney U and Fisher's test used to compare between groups with p <.05 considered significant. Youth with (n = 23) and without (n = 23) PWS were similar in age and sex distribution. The PWS group had a lower energy intake (p ≤.001), higher nutrient density (p =.003), and better adherence to guidelines (p =.007) compared to the control group. The proportion with nutrient intake from food below Estimated Average Requirement or Adequate Intake were similar between groups. Fiber, vitamin D, calcium, and potassium intake were below recommendations in 50% or more in both groups. The inclusion of supplement intake lowered the proportion below recommendations, except for fiber and potassium. Youth with PWS had a similar nutrient intake as those without PWS despite a lower energy intake, which could be attributed to higher diet quality. However, more than half of youth with PWS were at risk of inadequate fiber, vitamin D, calcium, and potassium intake. A greater emphasis on nutrient‐dense foods would improve nutrient intake, but supplements may be warranted in youth with PWS who do not meet recommendations. [ABSTRACT FROM AUTHOR]

Although gut microbiota has been suggested to play a role in disease phenotypes of Prader–Willi syndrome (PWS), little is known about its composition in affected children and how it relates to hyperphagia. This cross-sectional study aimed to characterize the gut bacterial and fungal communities of children with PWS, and to determine associations with hyperphagia. Fecal samples were collected from 25 children with PWS and 25 age-, sex-, and body mass index-matched controls. Dietary intake data, hyperphagia scores, and relevant clinical information were also obtained. Fecal bacterial and fungal communities were characterized by 16S rRNA and ITS2 sequencing, respectively. Overall bacterial α-diversity and compositions of PWS were not different from those of the controls, but 13 bacterial genera were identified to be differentially abundant. Interestingly, the fungal community, as well as specific genera, were different between PWS and controls. The majority of the variation in the gut microbiota was not attributed to differences in dietary intake or the impact of genotype. Hyperphagia scores were associated with fungal α-diversity and relative abundance of several taxa, such as Staphylococcus, Clostridium, SMB53, and Candida. Further longitudinal studies correlating changes in the microbiome with the degree of hyperphagia and studies integrating multi-omics data are warranted. [ABSTRACT FROM AUTHOR]