A study published in the journal Human Molecular Genetics by researchers at Children's Hospital Los Angeles (CHLA) provides novel insights into the brain mechanisms underlying the insatiable hunger and subsequent obesity in patients with Prader-Willi syndrome.
Prader-Willi syndrome (PWS) is a rare genetic disease characterized by hyperphagia - a chronic feeling of hunger that, coupled with a metabolism that utilizes drastically fewer calories than normal, often leads to excessive eating and obesity in patients with the disease.
It affects approximately 1 in 25,000 births about 350 to 400,000 individuals worldwide, and is recognized as the most common genetic cause of life-threatening childhood obesity.
Although much attention has been focused on the metabolic and behavioral outcomes of PWS, scientists still knew relatively little about the consequences of PWS on development of appetite-related brain pathways in the hypothalamus.
This portion of the brain develops during neonatal life under the influence of both environmental and genetic factors. It has been suggested that, due to its importance in the control of eating and energy balance, early impairments of hypothalamic development may result in lifelong metabolic dysregulation.
"Our goal was to characterize the development of brain circuits involved in appetite regulation, using a mouse model for Prader-Willi syndrome. We specifically focused on the hypothalamus because it is the brain region critical for regulation of homeostatic processes such as feeding," said lead author Sebastien Bouret, PhD, a member of The Saban Research Institute's Developmental Neuroscience Program and an associate professor of Pediatrics at the Keck School of Medicine of the University of Southern California (USC).
Bouret and colleagues found that mice lacking Magel2, one of the genes responsible for PWS, display abnormal development of the brain connections that normally trigger satiation, telling the body it has gotten enough to eat. They also report that these neurodevelopmental defects are unlikely to involve endocrine factors - hormones that regulate things like metabolism, growth and development. Rather, the gene Magel2 itself appears to have a direct effect on axonal growth.
Based on previous findings showing a pivotal role for the metabolic hormones leptin and ghrelin in hypothalamic development, the scientists measured their levels in Magel2 knockout mice, comparing them to control mice. They found that the knockout mice had normal levels of leptin and ghrelin, suggesting that the loss of Magel2 alone leads to the disruption of hypothalamic feeding circuits, an effect independent of the effects of those metabolic hormones.
Additional contributors to the study include first author Julien Maillard, Children's Hospital Los Angeles and INSERM, Jean-Pierre Aubert Research Center, University Lille, France; Soyoung Park, Sophie Croizier and Joshua H. Cook, Children's Hospital Los Angeles; Charlotte Vanacker and Vincent Prevot, INSERM; and Maithé Tauber, INSERM and Children's Hospital, Toulouse, France.
This work was supported by the Foundation for Prader-Willi Research, the National Institutes of Health (Grants R01DK84142, R01DK102780, and P01ES022845), the United States Environment Protection Agency (Grant RD83544101), and the EU FP7 integrated project.
About Children's Hospital Los Angeles
Children's Hospital Los Angeles has been named the best children's hospital on the West Coast and among the top five in the nation for clinical excellence with its selection to the prestigious U.S. News & World Report Honor Roll. Children's Hospital is home to The Saban Research Institute, one of the largest and most productive pediatric research facilities in the United States. Children's Hospital is also one of America's premier teaching hospitals through its affiliation since 1932 with the Keck School of Medicine of the University of Southern California. For more information, visit CHLA.org or visit our blog at ResearCHLAblog.org.
Debra Kain | EurekAlert!
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
05.12.2016 | Power and Electrical Engineering
05.12.2016 | Materials Sciences
05.12.2016 | Power and Electrical Engineering