Is being overweight and thin a matter of genes? For the general population, this influence is around 20%, according to studies that in recent years have analyzed the complete genome of tens of thousands of people. In other words, “lifestyle, such as eating habits and exercise, have a great impact, but Genetic factors also play a role.«, explains researcher Nerea Deleyto Seldas, from the Centro Nacional de Investigaciones Oncológicas (CNIO).
Nearly a hundred genetic variants have already been identified that moderately increase the probability of having a high Body Mass Index (BMI). Now, researchers from the CNIO and IMDEA Food have just identified a new one. The work is published in the journal ‘Genome Biology’.
Variants of a gene are slightly different versions of that gene, which often do not result in visible changes in the body. But this variant affects the amount of fat that the body accumulates and is present in almost 60% of the European population.
For Alejo Efeyan, head of the Metabolism and Cellular Signaling Group at the CNIO, “the finding represents a further step in understanding the genetic components of obesity«. For her part, Ana Ramírez de Molina, director of the IMDEA Food Institute, considers that »knowledge of the implication of the cellular detection pathway for nutrients in obesity may have implications for the development and application of personalized strategies for the prevention and treatment of obesity. the obesity”.
Overweight and obesity are defined by an abnormal or excessive accumulation of fat that affects health. To search for genetic variants that influence the phenomenon, and the associated metabolic alterations, a team from IMDEA Food collected 790 healthy volunteers genetic material and data such as weight, Body Mass Index, amounts of total and visceral fat, amount of muscle mass; and waist and hip perimeters, among others.
The authors of the work analyzed the possible associations of these parameters with 48 specific genetic variants, selected for their possible functional relevance. They thus detected a “significant correlation between one of these variants in the FNIP2 gene, and many of these parameters related to obesity,” explains the study.
The effect of this variant was then studied in mice -which had previously been genetically modified to express it-. “We verified that mice with this variant, associated in people with a thin constitution, have between 10% and 15% less fat than their non-carrier counterparts,” explains Efeyan.
In humans, the effect of this variant cannot be isolated from that of many other genetic and environmental variables that influence physical constitution, so it is impossible to accurately calculate the power of its effect. But since the influence of genetics on obesity does not exceed 20%, the contribution of the variant now identified is necessarily small. «Does not aboutnot at all, that those who have this version can overeat without gaining weight“Efeyan clarifies.
The genetically modified animals for this study did not present other alterations or differences. “This result is very shocking, because many of these studies tend to limit themselves to reporting associations; in this work we show that the change of a single letter in the entire mouse genome is enough to replicate what is observed in the human variant”, continues Efeyan.
The importance of the variant detected lies in the fact that it is associated with the biochemical signal pathway that tells the cell what nutrients are available. Now we have to study why a small genetic change affects the tendency to be thin.
The goal in the future is “to better understand the molecular bases of what this genetic variant does, that is, what is happening to the cell biochemically,” adds Nerea Deleyto. “We need to improve the genetic tools to dissect when the functional consequences of this variant in the organism become important, for example, during the process of fat formation,” she emphasizes.
The finding also raises questions that concern other areas of science, such as what evolutionary pressures favored the selection of this variant and when it occurred.