Identification of a gene related to the great obesity
(France-Amerique,22 Nov)

The discovery (1) by a Franco-English team of a new gene implied in the predisposition to massive obesity, while acting at the same time on the food behavior and the production of insulin, represents without question an interesting projection in the comprehension of part of the genetic maze of obesity.

But it does not explain all. The environment in the broad sense, food bad habits that the Anglo-Saxons translate by the picturesque term of "toxic food" and accelerated sedentarisation take part in this epidemic galopante which concerns today more than 300 million individuals in the world. In France more than 14 million people are in overweight and 5,3 million is frankly obese.

France must engage in a firm policy of prevention of obesity of the child, recalled last week the Academy of medicine and the Academy of pharmacy, informing that if nothing is done to stop the tendency of these thirty last years, a small child on four will be too large in 2020 in our country.

After ten years of efforts, the Franco-English researchers, under the direction of professor Philippe Froguel, thus succeeded in showing that the changes of gene baptized today GAD 2, increase the predispositions to develop a severe obesity (more than 100 kilos for 1,65 m), an affection which strikes 1 % of the French but 5 % of the North-American ones.

Already in 1998 (2), the same team had succeeded in locating this gene then baptized "Ob1" on chromosome 10. At the time, professor Philippe Froguel, very optimistic, estimated from 12 to 18 months time necessary to identify this gene precisely.

"But we had underestimated the difficulties", recognizes without sorrow today this specialist who directs two teams of the English Channel on both sides, one for CNRS at the university of Lille-II, the other in Hammersmith Genome Centre with the Imperial College of London.

"One realizes well that the human genetics, it is much more complicated than than one imagined at the beginning"

This gene GAD 2, located on chromosome 10, accelerates, by the intermediary of an enzyme, the production of a neurotransmettor, Gaba (acid gamma-aminobutyrique).

This last stimulates the appetite, while acting on the level of the hypothalamus in the brain. Moreover, the gastric hormone which decreases the food catch in the human being, intervenes by a mechanism which also utilizes Gaba (3).

"Gaba is in the center of an intestinal network and neuronal complex which ensures the permanence of an ideal weight by maintaining a balance between the effects of the molecules supporting the appetite and thus the catch of weights and those which have an opposed effect", explain the researchers.

The changes of genes intervening in the regulation of this balance can thus have effects on the overweight. After having compared 575 large obese to 646 individuals of standard weight, they succeeded in identifying on this gene two types of genetic variability (polymorphism), one protective, the other facilitator of obesity.

The researchers highlighted an activity of gene six times higher at "the very large ones". This surexpression of gene could thus increase the quantity of the Gaba neurotrans-setter on the level of the hypothalamus and its accelerating effect of the food catch.

"These people have great difficulties in control their food catch. They eat without hunger. But it is about a genetic feature which overrides cultural factors of behavior ", summarizes professor Froguel.

In addition, this gene is strongly present in the cells of the pancreas which manufactures the insulin (which makes decrease the sugar rate in blood). However this hormone secreted normally during the food catch has a powerful effect growth regulator, it contributes to satiety. The abnormal gene delays the production of insulin with for consequences an increase in the hunger and a reduction in the satiety which, by increasing the catch of food, takes part in the development of this severe obesity.

With the question of knowing if such a discovery will lead to the development of drugs, professor Froguel remains careful "I do not know anything of it", answers it, while recognizing that there will be no pill miracle of obesity.

It is essential to better include/understand the complexity of the genetics in the human being. On the other hand that should make it possible to better include/understand why certain people are more sensitive to a noxious environment, that of the "toxic food".

This work, initially, of 1998 to 2002 summer carried out with the financial collaboration of the laboratories Eli Lilly. "They ceased helping us last year but they on the other hand gave us the intellectual property of the discovery. So that the patent of this gene is held today by CNRS.

A so rare event that it should be underlined ", jubile it. For better including/understanding the share of the genetics in the causes of severe obesity in the child this time, the team of professor Froguel seeks 500 French families having one or more children in overweight.
By Catherine PETITNICOLAS.