Dallas, TX, United States, 10/12/2021 / Source: University of Virginia Health System /
University of Virginia scientists have identified 14 genes that can cause obesity and three genes that can prevent weight gain. The findings are important for treating a condition that affects almost 40% of American adults.
Eyleen O’Rourke of UVA’s College of Arts & Sciences, the School of Medicine’s Department of Cell Biology, and the Robert M. Berne Cardiovascular Research Center said “We know of hundreds of gene variants that are more likely to show up in individuals suffering obesity and other diseases. But ‘more likely to show up does not mean causing the disease. This uncertainty is a major barrier to exploit the power of population genomics to identify targets to treat or cure obesity. To overcome this barrier, we developed an automated pipeline to simultaneously test hundreds of genes for a causal role in obesity. Our first round of experiments uncovered more than a dozen genes that cause and three genes that prevent obesity,”
She further added that “We anticipate that our approach and the new genes we uncovered will accelerate the development of treatments to reduce the burden of obesity.”
Obesity and Our Genes
O’Rourke’s new research sheds light on the complex interaction of our DNA, diet, and obesity. Obesity has become an epidemic driven largely by high-calorie diets laden with sugar and high fructose corn syrup. The increasingly sedentary lifestyle of the population also plays a large role in obesity. But our genes also play an important role too, regulating fat storage and how our body burns food as fuel. If we can identify genes that convert excessive food into fat, we can seek to inactivate them using drugs and unlink obesity from excessive eating.
Genomicists have identified hundreds of genes responsible for obesity- this means that genes are more or less prevalent in people who are obese than in people with a healthy weight. The challenge lies in determining which genes play casual roles by directly promoting or helping prevent weight gain. To differentiate between genes O’Rourke and her team turned to humble worms known as C. elegans. These tiny worms live in rotting vegetation and enjoy feasting on microbes. However, these worms share more than 70% of their genomes with humans and like us become fat if their diet contains excessive amounts of sugar.
The worms have been quite beneficial for science as they’ve been used to understand how common drugs including antidepressant Prozac and glucose stabilizing metformin work. Impressively, three Nobel prizes were awarded in the last 20 years for the discovery of cellular processes first observed in worms but later found to be critical to diseases such as cancer and neurodegeneration. These worms have also been crucial to the development of drugs and therapeutics based on RNA technology.
O’Rourke and her team used these worms to screen 293 genes associated with obesity in new work published in the scientific journal PLOS Genetics, with the goal of identifying which genes were causing or preventing weight gain.