Discovery of 17 Genes Implicated in Obesity Could Lead to Breakthrough Treatments

At the end of September, scientists from the University of Virginia revealed the discovery of 17 total genes directly implicated in the development of obesity. It is an important breakthrough as the COVID-19 pandemic has only served to escalate this persistent and often overlooked crisis.

It’s no secret that rates of obesity prevalence for both child and adult populations have been steadily increasing over the last two decades. In a recent media statement, the Centers for Disease Control and Prevention reported that the number of states in which 35% or more of the population had obesity almost doubled from nine in 2018 to 16 in 2020. Further literature analysis of COVID-19 patients found that children suffering from obesity had greater severity of illness and higher rates of hospitalization.

As this invisible epidemic continues to rage in the shadow of COVID-19, Dr. Eyleen O’Rourke, Ph.D. and her team have been working to understand the genetic factors behind obesity.

“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,” said O’Rourke, an assistant professor of biology and cell biology at the UVA School of Medicine’s department of cell biology and 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.”

While the research team was largely composed of members from UVA, additional members represented Sweden’s Uppsala University, the Broad Institute of MIT and Harvard. Together, the researchers were able to comb through hundreds of genes known to be associated with obesity and pinpoint a select few with promising implications.

“Anti-obesity therapies are urgently needed to reduce the burden of obesity in patients and the healthcare system,” O’Rourke stated in the press release. “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.”

Intrigued, BioSpace spoke with O’Rourke in an effort to learn more about the findings.

Shedding Light on the Unseen

By developing a model of obesity for the oft-studied worm C. elegans, with whom we share a 70% genetic similarity and a comparable weight-gain response to overeating sugar, O’Rourke and her team screened 293 genes suspected of committing obesity-causing cellular crimes.

Of these, a total of 17 genes stand formally accused: those that are implicated in obesity causation number 14, while three have been shown capable of playing preventative roles.

O’Rouke noted that obesity is a complex disease, and that progress toward definitive mechanistic answers is slow-going. “Even when we get really accurate answers, those answers are restricted to this particular context,” she told BioSpace, elaborating that the activity of those genes might change if C. eleganswere fed a different, non-high-fructose diet. “Now this gene [may not be] doing anything. Not surprising, we have found many cases in which it’s doing the opposite: Instead of reducing fat levels, it’s increasing current levels if I change the diet in a different way.”

However, since the genes being screened were already associated with obesity, the results are still promising. Even better, blocking the activity of a specific preventative gene appeared to improve the neurolocomotory function and increase longevity in C. elegans, two traits that are negatively influenced by obesity in humans.

This seems to be hope enough to fuel O’Rourke’s drive to uncover more pieces of the human body’s metabolic puzzle. In the meantime, she encourages more expansive research, saying, “it’s important to stay open-minded with respect to the value of lower model systems, and also newer systems, because who says that flies, or mice, or C. elegans offer us the best approximation to human physiology? “I’m sure there are a lot of things out there in nature that could be very informative that we’re just not looking into.”

Obesity: The Invisible Epidemic

Since the Office of the Surgeon General issued a Call to Action in 2001, obesity has been an on-again, off-again talking point. But, lack of publicity isn’t the cause of obesity: in fact, the exact causes of obesity are numerous and varied, ranging from available diet options to fitness choices and individual heredity.

This complexity is the reason why, despite Michele Obama’s 2008-2016 school health initiatives and copious ‘healthy’ options on food service menus, the rates of childhood obesity continue to climb. Results from the 2017-2018 National Health and Nutrition Survey showed that approximately 16.1% of children in the U.S. between the ages of 2 and 19 years old were overweight and 19.3% of them had obesity, which includes the 6.1% suffering from severe obesity. A related survey completed over the same time frame evaluated rates of adult obesity and found that the prevalence of adults suffering from the condition was a whopping 42.4%.

If only the buck stopped there. Unfortunately, childhood obesity is likely to develop into adulthood obesity, which in turn increases the risks for heart disease, Type 2 diabetes and even some cancers. In total, obesity costs patients and insurers upwards of $147 billion a year. That averages out to $1,429 more in medical costs for each adult suffering from obesity.

Genetics: The Invisible Mastermind

It’s common opinion that patients suffering from obesity have only themselves to blame, and this opinion permeates our society from fashion magazines to emergency rooms, even in the most well-meaning cases. However, the complex pathways between interconnected systems that govern the body’s fat storage are yet to be completely understood.

Research has shown that certain environmental factors are undoubtedly in play: social class, education, ethnicity and gender can all affect a given person’s access to food, as well as the nutritional value of that food. Furthermore, studies show that experiencing a certain degree of stress can cause the body to modify certain epigenetic markers and that some of these modifications could be both linked to obesity as well as transgenerational inheritance.

In short, this means that obesity is not only less voluntary than often represented in the commercial media, but it could also be heavily influenced by a number of inheritable variables. Even more morose is that the right mix of stress and poor nutrition could introduce these genetic variables into a family’s medical history ‘spontaneously’ – meaning that researchers and medical professionals might be staring down the equivalent of one-off genetic changes that could suddenly appear in millions of current and future Americans, without any traceable origin.

It’s a sobering thought that necessitates more studies and breakthroughs like this one.