Researchers from the University of Virginia Health System have discovered 14 genes that cause obesity. They also identified three genes that could prevent weight gain. The findings will hopefully lead to the development of new medicines that target obesity. Since over 40% of Americans suffer from obesity, finding new ways to combat the epidemic is crucial.
“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,” said 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.
“We anticipate that our approach and the new genes we uncovered will accelerate the development of treatments to reduce the burden of obesity,” she said.
Scientists identify genes that cause obesity
The new findings reveal the complex relationships between obesity, diet, and our genes. In the last few decades, obesity rates have increased dramatically due mainly to our lifestyles. We have access to an abundance of food choices. However, most of them have little nutrition. Instead, they have high amounts of sugar, high-fructose corn syrup, and vegetable oils, which pack on calories. Coupled with our increasingly sedentary lifestyles, it’s a recipe for disaster.
However, even though lifestyle choices play a significant role in the obesity epidemic, we also must consider our genetic makeup. Some people have more genes that cause obesity, making them more susceptible to gaining weight. Our genes help regulate fat storage and impact our bodies’ ability to burn calories for energy.
So, by pinpointing the genes that transform excess calories into fat, scientists could develop drugs to inactivate them. This way, any extra calories won’t turn into fat, and we’d begin to turn a corner in fighting obesity.
Genomicists have found hundreds of different genes that cause obesity. Compared to people with a healthy weight, overweight people have more of these genes. However, only a handful of these genes directly contribute to or prevent weight gain.
To identify the 14 genes that cause obesity, O’Rourke and her colleagues referred to tiny worms called C. elegans. These worms typically live in decaying vegetation and feed on microbes. Despite the apparent differences between humans and these worms, we share 70% of our genes. Just like people, they suffer from obesity when given a diet high in sugar.
The worms have been incredibly beneficial for scientific research. So far, they’ve been used to figure out the mechanisms behind drugs like the antidepressant Prozac and the glucose stabilizer metformin. In the last two decades, scientists have also discovered cellular processes in the worms that can help treat diseases like cancer and neurodegeneration. In the past 20 years, three Nobel prizes have been awarded for these essential discoveries. Finally, they’ve been crucial to the development of therapies based on RNA technology.
How the worms helped show how people become obese
In new research recently published in the scientific journal PLOS Genetics, O’Rourke’s team tested their theory on the worms. They used them to screen 293 genes linked to obesity in humans to pinpoint which genes specifically triggered or prevented the disease. They created a worm model of obesity to perform the research, dividing the worms into two groups. Then they fed the first group a regular diet, and the others were given a high-sugar diet.
Using the obesity model, automation, and supervised machine learning-assisted testing, they identified the 14 genes that cause obesity. In addition, they discovered the three genes that help prevent it. During their research, they also made other promising findings. When the team inhibited activation of the three genes preventing obesity in the worms, it increased their lifespan and improved their neuro-locomotory function. Hopefully, anti-obesity drugs would replicate these benefits in humans as well.
Of course, they’ll have to do more research to confirm the findings. However, researchers say the initial studies are encouraging. For instance, blocking the activation of one of the genes in lab mice prevented weight gain. It also improved insulin sensitivity and decreased blood sugar levels. The scientists believe replicating this experiment in humans would produce the same results since the genes studied have also been linked to human obesity.
What factors cause people to become obese?
Since obesity can cause other health problems like diabetes, heart disease, and even cancer, it must tackle this epidemic. According to the World Health Organization, these lifestyle factors can help prevent obesity:
- limit calories from total fats and sugars;
- increase intake of fruits, vegetables, legumes, whole grains, and nuts; and
- make physical activity part of your routine (60 minutes a day for children and 150 minutes spread through the week for adults)
“Anti-obesity therapies are urgently needed to reduce the burden of obesity in patients and the healthcare system,” O’Rourke said. “Our combination of human genomics with causality tests in model animals promises yielding anti-obesity targets more likely to succeed in clinical trials because of their anticipated increased efficacy and reduced side effects.”
Obesity affects millions of people not just in the United States but globally as well. Scientists have even observed weight gain in pets and wild animals over the years! Clearly, it’s become a crisis that warrants urgent action. Luckily, researchers believe they’ve made a breakthrough, at least in regards to human obesity.
A team from UVA recently discovered 14 genes that cause obesity. In their research, they found that preventing activation of specific genes decoupled overeating from detrimental health effects. Also, it had other unexpected results – increased lifespan and improved neuro-locomotory function. The team believes anti-obesity drugs would replicate these findings in humans as well.