A study on obesity carried out on 800,000 people questions a historical theory

A genetic study conducted in Nancy on more than 800,000 people calls into question the theory of “economical gene”, long used to explain obesity. However, These results open up new perspectives to better understand and treat certain forms of disease.

A vast genetic study conducted by the professor. For example, director of the nutrition, genetics and exposure to environmental risks of Inserm David Meyre and his doctoral student Sandra El Kouche, invalidates the famous theory of “economical gene”, which has long dominated the scientific explanations on obesity and diabetes.

A discovery that changes our gaze on the history of our genes, and opens up new medical perspectives.

The old theory that had marked research – Study obesity carried out 800,000

In 1962. Moreover, the American doctor James Neel formulated an hypothesis which has become famous: the theory of “economical gene”.

The idea seems simple and logical. Similarly, study obesity carried out 800,000 In a world where famine was frequent, some individuals would survive better because their body knew how to store fat. In addition, These “good storage” therefore transmitted their genes more to the following generations. Meanwhile, But in our modern societies. However, characterized by food abundance and sedentary lifestyle, these inherited genes would become a handicap, promoting the explosion of obesity and type 2 diabetes. Meanwhile,

To support his theory. Moreover, James Neel was particularly based on the example of the Indians Pimas d’Arizona, who, after going from a traditional lifestyle to a Western diet, experienced an outbreak of obesity and diabetes. Furthermore,

It is this theory that David Meyre and Sandra El Kouche question.

An attractive hypothesis but never proven – Study obesity carried out 800,000

For more than 60 years. Therefore, the theory of the economical gene has been supplying scientific debates. However, “” study obesity carried out 800,000 Half of the community believed in it, the other half rejected it. Therefore, But no one really had massive data to decide “Explains Professor Davis Meyre.

This vagueness was starting to annoy him: ” I have been working on genetics. Therefore, obesity since 2001, and I thought it was time to provide a clear answer. »» With his doctoral student, Sandra El Kouche, he then launched into a study of unprecedented magnitude.

800,000 genomes screened – Study obesity carried out 800,000

Thanks to a public database, the team analyzed the exomes and genomes of more than 800,000 people, from seven large ethnic groups (Europeans, African, Latin American, Middle East, Asians of the East and South, Jews study obesity carried out 800,000 Ashkenazes).

Attention was paid to 73 genes already known for their role in rare forms of obesity:

• 65 linked to syndromic obesity. which combines severe obesity and other disorders (mental delay, malformations, etc.);

• 8 Linked to monogenic obesity, where the main symptom is excessive hunger and very rapid weight gain.

Without appeal results

Contrary to what James Neel suggested, the researchers found no evidence that these changes were advantageous in the past.

• For genes linked to syndromic obesity, mutations even have a negative signature of natural selection. In other words, they were rather disadvantageous and eliminated over the generations.

• For genes of monogenic obesity, no trace study obesity carried out 800,000 either of an evolutionary advantage. Their presence is compatible with a neutral model, that is to say due to chance and not to environmental pressure.

• Finally, the researchers excluded the idea of ​​a natural selection “balanced” (mutations sometimes advantageous, sometimes unfavorable depending on the context).

« Clearly, our results show that these genes are not relics to adapt to famines. Their current distribution is rather genetic drift, chance of the history of human populations Summarizes David Meyre.

Obesity: an equation at 50/50

These conclusions do not mean that genes have nothing to. do with obesity. On the contrary. “” Obesity is 50% genetic and 50% environment Reminds the researcher.

On the one hand. there are many inherited individual differences: some people are biologically more inclined to store energy than others. But on the other. the modern environment (processed foods, rich in study obesity carried out 800,000 sugars and fat, sedentary lifestyle) plays a major role that is just as devious.

Good news: that means that a risk genetic profile is not a formality. “” We have shown that some genes slightly increase weight. but that the effect disappears completely in people who practice intensive physical activity », Illustrates David Meyre.

A direct medical impact

Beyond the theoretical debate, this study has concrete benefits. Because certain genetic forms of severe obesity can now be treated.

« Today we have targeted drugs that directly correct genetic defect. Patients can lose up to 70 kilos without changing anything in their lifestyle. simply because the biological cause is corrected “, Underlines the professor.

This is why the study obesity carried out 800,000 Nancy team develops genetic screening programs in a hospital environment. Knowing the changes in a population allows you to better decide when offering a suitable test and treatment.

Another striking observation: according to ethnic groups. the frequency of certain genetic mutations can vary to be six times higher from one population to another. Hence the importance of having diversified genetic data to develop medicine adapted to each patient.

And now ?

The study does not close the door to new research. “” Our results concern seven major groups, which represent billions of people. But we have not yet studied certain specific populations. such as Pimas, the inhabitants of the Pacific Islands or the Bedouins of the deserts. These extreme contexts could provide other lessons “, Specifies David Meyre.

The team also wants to explore another question: if our genome has not study obesity carried out 800,000 adapted to the famines of the past. will he be able to adapt to the chronic supercharging of the present? Nothing is less certain, warn the researchers.

Despite the complexity of the subject. the professor insists on a strong idea: genetics does not condemn. “” Yes, there are risk genes, but also genes that promote thinness. And above all, the genes interact with our lifestyle. A favorable environment can compensate for a predisposition.«

In the future, the objective is clear: developing personalized programs combining genetics, prevention and treatments to better combat obesity.

Léa Canet