This result was published in Nature Genetics on January 18th 2009 by a research group led by CNRS senior researcher Philippe Froguel and Inserm researcher David Meyre from the laboratory "Génomique et physiologie moléculaire des maladies métaboliques" (1), in association with their British colleagues from Imperial College.
This study, run in collaboration with French, Finnish, Swiss, Canadian and German researchers, has led to the discovery of three new genes that increase the risk not only of severe obesity but also ordinary weight gain in the population. It underlines that there is no difference between being overweight and other forms of obesity (mild, severe or massive).
Obesity is spreading throughout the world like an epidemic. For the first time in history, obesity-related health problems (like type 2 diabetes (2), heart disease and cancer) could reduce the life-expectancy of today’s children by several years compared with their parents’ generation. Even though the increase in the number of obese people over the two last decades is partially due to social causes (inactivity, junk food, etc.), heredity plays an important part in determining body weight (70% hereditary) and the occurrence of obesity, especially when this is severe and appears early in life.
First genetic map of obesity
Froguel’s team has been working for 15 years to better understand the molecular basis of type 2 diabetes and the obesity found in 80% of diabetics. Their work has revealed several genes responsible for monogenic forms of obesity and has demonstrated the essential role these genes play in appetite control. Since a full map was established of human genetic variations, it has been possible to study all the genes implicated in the genetic predisposition to obesity using DNA microarrays. With joint funding from the ANR (3), Région Nord Pas-de-Calais and the British Medical Research Council, French and British researchers have combed through the complete genomes of 2796 French volunteers, 1380 of which had severe familial obesity, compared with 1416 lean subjects. The genetic mutations most likely to cause obesity were then analyzed in 14,000 samples from French, Swiss, German and Finnish populations.
The scientists, led by Froguel and Meyre, first confirmed that the genes FTO and MC4R (4) played a major role in susceptibility to common obesity and weight gain in the population as a whole. These two genes work by controlling eating behavior.
Three new genes associated with obesity and weight gain identified
The researchers also found variations in the DNA close to the genes MAF and PTER (5), and directly in the coding sequence of the NPC1 gene. These genetic polymorphisms, widespread in European populations, alter the general population’s risk of severe obesity and weight gain throughout their lifetime. The NPC1 gene has more than 200 pathogenic mutations responsible for Niemann-Pick type C disease, a progressive neurodegenerative condition. Mice without NPC1, and which also have neurological disorders, also lose weight and have no appetite. The mutation associated with obesity could therefore directly induce an increase in the function of the NPC1 protein, such that it would work too well if the gene had mutated. As for the MAF gene, it codes for a particular protein involved in the differentiation of adipose tissue (tissue responsible for fat storage) and in the production of a digestive hormone involved in satiety and insulin secretion. The last gene (PRL) is more particularly associated with obesity and weight gain in adults. PRL produces prolactin, a hormone well known for its effect in stimulating lactation in women. Prolactin also plays a role in controlling the amount of food we consume.
Combined with the genetic approaches conducted on the general population, this work reveals that the study of family forms of obesity is particularly useful for understanding the genetic causes of obesity. They demonstrate the fundamental role of eating behavior in the regulation and evolution of human corpulence and in the incidence of severe childhood obesity. In the long term these results should allow the early identification of children at risk of obesity and the development of personalized preventive and therapeutic medical strategies.
These results were obtained with the help of volunteer families with obese children and/or adults. To continue the research, it is essential to have DNA from a maximum number of French subjects.(1) CNRS/ Université Lille 2 Droit et Santé/ Institut Pasteur de Lille.
(5) This gene has no known function at present.
Julien Guillaume | alfa
Further reports about: > Cancer > DNA > DNA microarray technology > MAF > NPC1 > Nature > Overweight > PTER > appetite control > general population > genetic map > genetic mutation > genetic variation > heart disease > hereditary illness > human genetic variations > inactivity > junk food > ordinary weight gain > type 2 diabetes
Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München
Second research flight into zero gravity
21.10.2016 | Universität Zürich
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences