Hyperphagia: Current concepts and future directions proceedings of the 2nd international conference on hyperphagia

Abstract

Objective Hyperphagia is a central feature of inherited disorders (e.g., Prader–Willi Syndrome) in which obesity is a primary phenotypic component. Hyperphagia may also contribute to obesity as observed in the general population, thus raising the potential importance of common underlying mechanisms and treatments. Substantial gaps in understanding the molecular basis of inherited hyperphagia syndromes are present as are a lack of mechanistic of mechanistic targets that can serve as a basis for pharmacologic and behavioral treatments. Design and Methods International conference with 28 experts, including scientists and caregivers, providing presentations, panel discussions, and debates. Results The reviewed collective research and clinical experience provides a critical body of new and novel information on hyperphagia at levels ranging from molecular to population. Gaps in understanding and tools needed for additional research were identified. Conclusions This report documents the full scope of important topics reviewed at a comprehensive international meeting devoted to the topic of hyperphagia and identifies key areas for future funding and research.

Prader-Willi, Angelman, and 15q11-q13 Duplication Syndromes

“…Belonarib is an inhibitor of methionine aminopeptidase-2 and works to reduce fatty acid synthesis, insulin levels, and food consumption. It also increases mobilization of fats and energy expenditure 40 .…”

Zebrafish Models of Prader-Willi Syndrome: Fast Track to Pharmacotherapeutics

“…Sim1 heterozygous mice display hyperphagic obesity and reduced oxytocin expression in the hypothalamus [23,24]. Oxytocin neurons that project to the hindbrain have been implicated in satiety [25,26]. Recently, a small 6q16 deletion that results in PWL as been identified.…”

“…For example, mutations in SIM1 , leptin receptor ( LEPR ), pro-opiomelanocortin ( POMC ), melanocortin 4 receptor ( MC4R ), and more recently, POU3F2 have all been associated with severe obesity, suggesting a convergence on the leptin-melanocortin pathway in association with oxytocin [25,27]. Mutations in zebrafish lepr , mcr4 , and pou3f2 have been generated, although few obesity-related studies have been performed as of yet.…”

Current and emerging therapies for managing hyperphagia and obesity in Prader‐Willi syndrome: A narrative review

“…Individuals with PWS require absolute control through one‐to‐one supervision to prevent choking and binge eating, which can lead to stomach rupture, gastric necrosis, and death . Excess energy intake can result in early onset morbid obesity and obesity‐associated complications, which are common causes of death in PWS . A few patients have a noticeable improvement in their appetite control and are able to feel full after they enter adulthood.…”

“…For most patients with PWS, hyperphagia continues into adulthood, posing persistent, life‐long risks to their health and safety. A frustrated lifetime of control and restricted lifestyle hinders their independence and significantly lowers the quality of life of these patients and their families …”