Researchers at the University of Virginia (UVA), in the United States, recently released a study, published in the scientific journal PLOS Genetics, in which they were able to identify 14 genes that can cause and three that can inhibit obesity. Considered by the World Health Organization (WHO) as a chronic disease, the disease currently affects 2.6 billion people worldwide, according to the United Nations (UN), and kills about 4 million a year.
Questioning a position of the US Centers for Disease Control and Prevention (CDC), the study disagrees with the argument that the increase in obesity in recent decades can be attributed to an “obesogenic environment, which offers easy access to high calorie foods, but it limits the opportunities for physical activity”. The research problem was: why, even sharing an environment that favors obesity, not everyone becomes obese?
To answer this question, the adopted hypothesis proposes that a considerable part of the weight variation among adults can be attributed to genetic factors. After all, it is already known that hundreds of genetic variants are more likely to appear in people suffering from obesity. However, “‘more likely to show up’ does not mean causing the disease,” explains one of the study’s authors, Eyleen O’Rourke, a professor at UVA.
Research methodology: the worms
C. elegans. (Source: Kbradnam/Wikipedia/Reproduction.)Source: Kbradnam / Wikipedia
The big challenge was to find out which genes convert excessive food into fat, and then disable them with some kind of medication and unlink the act of overeating from the occurrence of obesity. This is not just a matter of body aesthetics, but of eliminating a risk factor for serious comorbidities, such as cardiovascular and neurodegenerative diseases, diabetes, hypertension, stroke and cancer.
In the search for in vivo systems that would allow experimental tests with plausible yield and cost, O’Rourke and his team used worms Caenorhabditis elegans, an animal present in most genetic experiments. Thin, transparent and bisexual, these little animals of less than a millimeter inhabit the decaying vegetation and feast on microorganisms. But they share with us more than 70% of their genes. And they get fat.
Taking advantage of these similarities, the researchers developed an “obesity worm” model, feeding some of them a regular diet and others a diet rich in a kind of sugar of high sweetening power (fructose). They then started testing 293 obesity-associated genes in previous studies, to empirically prove which genes cause and which inhibit the disease.
Results obtained with the C. elegans
These obesity models were automated in an assisted machine learning system that allowed, among the myriad of data analyzed, to establish 14 genes that effectively cause obesity and three genes that inhibit it. More importantly, the discovery showed that by blocking the action of these three genes that keep worms from becoming obese, it also makes them live longer lives and better neurolocomotor function.
When the technique was extended to laboratory rats, it was able to prevent weight gain, improve insulin sensitivity and lower blood sugar levels.
ARTICLE PLOS Genetics: https://doi.org/10.1371/journal.pgen.1009736