Obesity is not a question of willpower and it is science that says it
Let us come back to what the life sciences have been able to highlight on this subject in recent years.
Remember that very recent advertising campaign from the gym channel Vita. It featured a woman with the following slogan: “Are you fat and ugly?” This is something else I would like to point out to you with this example. The poster of Vita Liberté implies that by taking out a subscription with them, it will be possible to lose weight. We have here, in 2015, a hint of the famous “eat less, move more”, resonating like the miracle recipe against obesity.
While the effects of physical activity on health and weight loss are well documented, the fact remains that investing in a sport over the long term is not just a matter of choice. Indeed, certain genes can influence the pleasure that we will take to practice a physical activity. This is a fact perfectly illustrated in the short story Eugene by Greg Egan where a doctor suggests to parents to influence the pleasure that their child will feel while practicing a physical activity by modifying some genes. Also, our social environment as well as our geographical area determines access to a sport. However, the genes that strongly influence the onset of obesity seem to act in the regulation of appetite. A recent review of the literature published in Nature Genetics looks back on the discovery of genes up to the understanding of the associated metabolic pathways.
Obesity in a few figures
First of all, the review reminds us of several essential figures. 39% of the world’s population is currently overweight and 12% are obese. This prevalence has tripled since the years 1975. If it tends to stabilize in developed countries, it is increasing dangerously in developing countries. Finally, the authors point out, citing studies that have followed twins, that obesity seems more or less hereditary: from 40 to 70%. In fact, you don’t choose to become obese. Our genetics and our environment largely determine disease.
From obesity to obesity
Obesity is the generic name to define the situation in which the body mass index (BMI) of an individual is greater than 30 kg / m2. First, we must differentiate between monogenic obesities in which a single mutation of a single gene is sufficient to generate the disease with polygenic obesity which corresponds to an accumulation of variants predisposing to obesity within the genome.
Polygenic forms are the most widespread at present and the biochemical mechanisms that these mutations alter are much better understood. The specialist’s comment is well corroborated by the review.
A metabolic pathway is extremely well studied by researchers in the field given its importance in the onset of obesity: the leptin-melanocortin pathway. Patients who have a genetic mutation that affects them do not feel full. Consequently, regulating food intake is extremely difficult for them, ”explains Amélie Bonnefond.
Ongoing clinical projects
We are trying to systematically sequence the genome of these patients because at the present time, the care of these patients is insufficient, points out the specialist before concluding, we have effective pharmacological treatments against this type of obesity, the diagnosis is therefore of crucial importance. Amélie Bonnefond refers here to Setmelanotide, a drug cited in the aforementioned review. We learn that after a year of regular injection in phase 3 clinical trials, patients with a particular form of obesity lose an average of 25.6% of their initial weight and 80% achieve weight loss by 10%. As for the harmful effects, they seem minor: hyperpigmentation, nausea and untimely erections. Nothing compares to the disasters that bariatric surgery can cause in these patients.
Gene and effect size
In the race to detect and identify genes associated with obesity, an important question remains: can progress in the discovery of the genes involved help us to significantly reduce, for example by 50%, the prevalence? current obesity? Our expert explains this point in detail: “Currently, studies are focused on the detection of frequent genetic variants, starting from the assumption that each variant predisposes a little more to the disease. However, when modeling, we notice that several alternative hypotheses can be considered. For example, some rare mutations may be involved in the polygenic forms of obesity. However, the gene in question will have a larger effect size than the others. ”
Beyond genetics
If our genome can predispose us to become obese, the environment is its accomplice. The foods we eat and the physical activity we do can have a positive feedback effect on the expression of our genes. This is the case with the Fat Mass and Obesity associated protein (FTO) gene, which studies show that lifestyle can reduce its effect on obesity by 30 to 40%. Unless we adhere to a dualistic philosophy of the mind (which postulates that the mind is of a different nature than the body.
A risk of obesity multiplied by 3 or 4 depending on the genetic profile
Obesity affects more than a billion people all over the planet, and its prevalence continues to grow: according to the World Health Organization, it almost tripled between 1975 and 2016. Children are also now heavily affected. by this disease, which constitutes a major risk factor for early mortality. Obesity increases the risk of the onset of several disabling diseases such as diabetes, stroke, cardiovascular disease, as well as various cancers, particularly of the breast or colon … In addition, obese people are also exposed to serious depressive and emotional illnesses.
In the general population, we now know that certain DNA variants (changes in the sequence of this molecule, the carrier of genetic information) increase the risk of increasing their weight and therefore of becoming progressively obese. These variations have been identified in several hundred regions of the genome, generally regulating the functioning of genes.
This discovery has recently made it possible to establish obesity risk scores, based on the genetic profiles associated with these variants. The conclusions are clear: People with a low risk score hardly ever develop obesity. They are therefore protected. In contrast, people with the profiles most associated with obesity have a 3- or 4-fold risk of becoming obese.
The genes involved in this so-called “common” form of obesity are mostly active in the brain. They are found in particular in regions that are involved in reward mechanisms and therefore addiction. Common obesity therefore results from a behavioral disorder in response to stress and accidents in life, coupled with hypersensitivity to the most addictive foods (such as sugar).
