Genes and obesity: new data

Biologists have discovered 14 genes that cause obesity, and three genes that prevent it

Maria Azarova, Naked Science

Obesity is called the main risk factor for the development of many diseases, such as neurodegenerative and cardiovascular diseases, as well as type II diabetes, hypertension, stroke and some types of cancer. Over the past decade, overweight has become the concomitant cause of four million deaths annually. In the future, experts fear, obesity may lead to a decrease in life expectancy. 

Because of all this, scientists are faced with the task of better understanding the causes of the formation of excessive fat deposits and developing new methods of fighting. However, it is difficult to determine effective intervention points for treatment, since obesity is a complex disease that is influenced by many factors. Among them are not only nutrition and low physical activity, but also socio–economic status, the composition of the intestinal microbiota and, of course, genes.

The increase in the number of overweight people can be explained, on the one hand, by the environment that provided us with easy access to high-calorie food, but limited physical activity. But not everyone in the modern world is completely obese. Therefore, scientists believe that a significant proportion of such cases can be associated with genetic factors.

More than 90 genome-wide studies of the association have revealed over 2.5 thousand differences in the DNA sequence of one nucleotide in size, which correlate with various indicators of obesity, including body mass index, waist-hip ratio, body fat distribution, and so on. Almost 90 percent of these variants were found in non-coding regions of the genome: consequently, very few of them could be compared with genes.

The authors of the new study – scientists from the University of Virginia (USA) and Uppsala University (Sweden) – tested the causal relationship between genes and obesity using a high-performance in vivo obesity screening system. The results of the work can be found in the journal Plos Genetics (Ke et al., Genes in human obesity loci are causal obesity genes in C. elegans).

"We know hundreds of gene variants that are more likely to be present in people suffering from obesity and other diseases. But that doesn't mean they cause the disease," explained Eileen O'Rourke of the University of Virginia. – Uncertainty was the main obstacle in order to use the possibilities of population genomics and identify targets for the treatment of obesity. To overcome this barrier, we have developed an "automated pipeline" for simultaneous testing of hundreds of genes for a causal role in obesity."

To begin with, scientists identified 340 candidate genes based on one of the published genome-wide association searches and took roundworms Caenorhabditis elegans. Since the end of the last century, geneticists have been actively using these nematodes with a length of about one millimeter as a model organism, since more than 70 percent of their genes coincide with human ones. C. elegans live in rotting vegetation and feed on microbes, and also suffer from obesity if they are fed sugar.

Using the example of worms (one group was put on a regular diet, and the other was given a lot of fructose), it turned out to test 293 genes associated with obesity in humans. By screening, the researchers identified 14 genes whose inactivation leads to excess body weight. Nematodes that actively consumed fructose not only had more body fat and were larger, but also had less robust health and did not live as long (by the standards of worms). Then, using this model, the researchers discovered three genes whose blocking prevented weight gain associated with nutrition, prolonged the life of C.elegans and improved their neuromotor function. 

According to the authors of the work, although – as always – additional research will be required, doctors expect the benefits described above from drugs for the treatment of obesity. "Our combination of human genomics methods with causality tests on model animals promises to achieve the goals of combating obesity and achieve success in clinical trials," the scientists concluded.

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