Scientists have discovered a gene variant that predisposes to thinness

Researchers have found that those who have a particular version of a gene involved in cell nutrition tend to accumulate less fat. (CREDIT: Creative Commons)

Researchers at the Spanish National Center for Cancer Research (CNIO) and the Food Institute IMDEA have found that those who have a certain version of a gene involved in cell nutrition tend to accumulate less fat.

But “this association does not mean that people with this genetic variant can overeat without getting fat,” says Alejo Efeian (CNIO), senior co-author on the paper with Ana Ramirez de Molina (IMDEA Food).

The work was published in the journal Genome Biology. The authors say this is a breakthrough in understanding the genetic components of obesity that could pave the way for future treatments for obesity.

How much do genes influence our weight? For the general population, this impact is estimated at 20%, according to studies that have analyzed the entire genome of tens of thousands of individuals in recent years. In other words, “lifestyle such as eating habits and exercise have a big impact, but genetic factors also have an impact,” explains researcher Nerea Deleito-Seldas of the Spanish National Cancer Research Center (CNIO).

Some of these genetic factors are already known. About a hundred genetic variants have already been identified that modestly increase the likelihood of having a high body mass index (BMI, a general measure of being overweight or obese).

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CNIO and IMDEA Food researchers have discovered a new one. Their work is published in the journal Genome Biology with Nerea Deleito-Seldas (CNIO) and Lara P. Fernandez of the IMDEA Food Institute as first co-authors.

Genetic variants are slightly different versions of a gene and most often do not result in visible changes in the body. But this particular variant matters: it affects the amount of fat stored in the body, and the authors of a new study show that it is especially common in Europe. It is estimated to be present in almost 60% of the European population.

According to Alejo Efeyan, head of the CNIO group on metabolism and cellular signaling, “this discovery is a step forward in understanding the genetic components of obesity.” Ana Ramirez de Molina, director of the IMDEA Food Institute, believes that “in-depth knowledge of the involvement of the cellular nutrient pathway in obesity may have implications for the development and application of personalized strategies for the prevention and treatment of obesity.”

Genetic and clinical data of 790 volunteers.

Overweight and obesity are defined as abnormal or excessive fat accumulation that affects health. To find the genetic variants that influence this phenomenon and the metabolic changes associated with it, a team from the IMDEA Food Institute collected genetic material and data such as body weight, BMI, total and visceral fat, muscle mass, waist and hip circumference, among other, from 790 healthy volunteers.

The researchers examined the possible associations of these parameters with 48 genetic variants selected on the basis of their potential functional significance. They found “a significant correlation between one of these FNIP2 gene variants and many parameters associated with obesity,” explains the study, which has just been published in the scientific journal Genome Biology.

Demonstration in animal models

The CNIO team then studied the effect of this variant in mice genetically modified to express it. “We found that mice with this variant, which is associated with thinness in humans, have 10-15% less body fat than their non-carrier counterparts,” explains Efeyan.

In humans, the effect of this variant cannot be isolated from the many other genetic and environmental variables that influence physical constitution, so it is not possible to accurately estimate the strength of its effect. But given that the influence of genetics on obesity does not exceed 20%, the contribution of the currently identified variant is necessarily small.

For this reason, researchers use terms like predisposition or tendency: “It’s not at all true that people with this genetic variant can overeat without getting fat,” Efeyan elaborates.

Animals genetically modified for this study showed no other changes or differences. “The observations in mice are very striking because many of these studies tend to be limited to reporting associations in the human population; in this paper, we show that a single letter change across the entire mouse genome replicates what we observed in the human variant.” Efeyan continues.

Associated with what the cell “eats”

This variant is present in a gene that is involved in a signaling pathway that tells the cell what nutrients are available. Now we need to study why a small genetic change affects the tendency to slim.

MiR-181b-5p binding to the 3’UTR of the FNIP2 T-allele. A TargetScanHuman predictions (for the genomic region rs2291007. Frequencies of B rs2291007 in European (EUR) and African (AFR) populations (https://www.ensembl.org/).

The goal for the future is “to better understand the molecular basis of the effects of this genetic variant, i.e. what happens to the cell biochemically,” adds Nerea Deleito. “We need to improve genetic tools for dissection when the functional consequences of this option are important in the body, for example, in the development of fat,” she emphasizes.

The discovery also raises questions for other areas of science, such as what evolutionary pressures drove this choice and when it happened.

To learn more about science and technology, visit our New Discoveries section at The bright side of the news.

Note: Material provided by Centro Nacional de Investigaciones. Content can be edited for style and length.

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