The new research, published in the scientific journal PLOS Genetics, helps shed light on the complex intersections of obesity, diet and our DNA. Obesity has become an epidemic, driven in large part by high-calorie diets laden with sugar and high-fructose corn syrup.
While a sedentary lifestyle plays a big part, our genes also have a role, regulating fat storage and affecting how well our bodies burn food as fuel. So if we can identify the genes that convert excessive food into fat, we could seek to inactivate them with drugs and uncouple excessive eating from obesity.
"We know of hundreds of gene variants that are more likely to show up in individuals suffering obesity and other diseases. But amore 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," said Eyleen O'Rourke of the University of Virginia's College of Arts and Sciences.
To determine which genes play causal roles by directly promoting or helping prevent weight gain, the team turned to humble worms known as C elegans. These tiny worms like to live in rotting vegetation and enjoy feasting on microbes. However, they share more than 70 per cent of our genes, and, like people, they become obese if they are fed excessive amounts of sugar.
Using the worms, the team screened 293 genes associated with obesity in people, with the goal of defining which of the genes were actually causing or preventing obesity. They did this by developing a worm model of obesity, feeding some a regular diet and some a high-fructose diet.
Besides identifying 14 genes that cause obesity and three that help prevent it, the team also found that blocking the action of the three genes that prevented the worms from becoming obese also led to them living longer and having better neuro-locomotory function.
Those are exactly the type of benefits drug developers would hope to obtain from anti-obesity medicines.
"Anti-obesity therapies are urgently needed to reduce the burden of obesity in patients and the healthcare system," O'Rourke said.