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Paris, July 18, 2005

A common gene for obesity and type 2 diabetes

The team led by Professor Philippe Froguel (CNRS, University of Lille 2), working with colleagues at Imperial College London and the University of California in Los Angeles, has recently identified the first genetic and physiological link between common childhood obesity, severe adult obesity and type 2 diabetes (1). This link is gene ENPP1, an inhibitor for the insulin receptor whose mutated versions, which are found in several local populations in Europe, are a source of resistance to insulin in the liver, the pancreas and probably the brain. These mutations are responsible for early-onset obesity and diabetes. These results open up new prospects for the understanding, prevention and treatment of “diabesity”, a condition in which obesity in children and adults is associated with its main medical complication, diabetes. The data on this were published on line on 17 July in the journal Nature Genetics.

Childhood obesity is a rampant epidemic around the world. In Europe, in 2005, nearly one child in every three is overweight and if nothing is done the vast majority will be obese in adulthood. Almost half will then develop diabetes and their life expectancy will be less than that of their parents. Sedentary lifestyles and poor nutrition are implicated at the societal level, but where the individual is concerned heredity plays a key role in determining the risk of contracting and these conditions and their severity. The CNRS team led by Philippe Froguel has helped identify the monogenic forms of childhood obesity in the years since 1998. However, until now, the genetic basis of the common (polygenic) forms of obesity in children remained undetermined.

 

In order to investigate this condition, researchers built up the largest collection of families with obese children anywhere in the world (2). Exploration of the entire genome of 115 French families made it possible to locate a region on chromosome 6 which predisposes a child to obesity, a region where the gene Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (ENPP1) is situated. This gene is an inhibitor for the insulin receptor whose excessive expression in the livers of transgenic mice leads to a lack of sensitivity to the effects of insulin and to a diabetic condition.

 

The current study, published in Nature Genetics, is based on a study of over 6,000 European individuals. It shows that the simultaneous presence of three mutations of the ENPP1 gene increases by between 50% and 70% the risk of developing obesity during childhood followed by massive obesity as a adult, and, to the same degree, the risk of contracting type 2 diabetes.

 

ENPP1 is the first genetic determinant shared by childhood obesity, morbid adult obesity and type 2 diabetes. The discovery of this gene for “diabesity” is important since it shows that in addition to dysfunction affecting dietary habits and satiety, there are types of obesity that are strongly causative of a type of diabetes that is purely metabolic in origin. Such obesity must be prevented and treated differently from diabetes linked to dietary behaviour. In this way, less “insulin-resistant” diets, high levels of physical activity or even special medication could prove effective in the struggle to contain “diabesity”, the first epidemic of non-infectious origin in the history of humanity. 

Notes:

(1) Non-insulin-dependent diabetes, also known as adult-onset diabetes. This type accounts for around 90% of cases.
(2) Freephone number: 0800 02 04 12.

References:

Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes. Nat Genet–2005
David Meyre, Nabila Bouatia-Naji, Agnès Tounian, Chantal Samson, Cécile Lecoeur, Vincent Vatin, Maya Ghoussaini, Christophe Wachter, Serge Hercberg, Guillaume Charpentier, Wolfgang Patsch, François Pattou, Marie-Aline Charles, Patrick Tounian, Karine Clément, Béatrice Jouret, Jacques Weill, Betty A. Maddux, Ira D. Goldfine, Andrew Walley, Philippe Boutin, Christian Dina, and Philippe Froguel

Contact information:

Researcher contacts:
Philippe Froguel and David Meyre
Laboratoire de génétique des maladies multifactorielles (Lille)
Tel: 03 20 87 79 54 - Fax: 03 20 87 72 29
E-mail: philippe.froguel@good.ibl.fr, meyre@good.ibl.fr
Web: View web site

Press contact:
Martine Hasler – Tel : 01 44 96 46 35 – E-mail: martine.hasler@cnrs-dir.fr

Department of Life Sciences contact:
Jean-Pierre Ternaux – Tel: 01 44 96 43 90 – E-mail: jean-pierre.ternaux@cnrs-dir.fr

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