A research team co-led by MIT professor (and NextGen alum) Manolis Kellis Kamvysselis and Harvard instructor Melina Claussnitzer has analyzed the genetics behind obesity, and discovered a new pathway, or genetic “master switch,” that controls human metabolism by prompting fat cells to store fat or burn it away.
This switch “decides whether calories will be stored as fat or whether they will actually be rued aways as heat,” Prof. Kellis told BBC. “You could say that we’ve found fat cells’ radiator, and how to turn it up or down,” Kellis explained in New Scientist.
The team’s experiments revealed that a faulty version of the gene causes energy from food to be stored as fat rather than burned. Genetic tinkering in mice and on human cells in the lab suggests this can be reversed, giving hope that a drug or other treatment might be developed to do the same in people.
“There’s a dogma that it all depends on appetite and exercise. That it’s your choice, and everything is decided by your brain,” says Kellis. “We’re showing that your fat cells have a very strong role in all this, independent of the brain.”
As reported by CBS, Kellis’ team’s work solves a big mystery: Since 2007, researchers have known that a gene called FTO was related to obesity, but they didn’t know how, and could not tie it to appetite or other known factors.
Previous studies have shown that FTO works in the brain and so may influence appetite and hunger, but the latest work suggests it exerts a more potent effect in fat cells themselves.
Kellis’s team was able to use gene editing techniques to adjust the functioning of the FTO gene in fat cells, converting fat-storing cells into fat-burning cells – and vice versa.
Prof. Kellis tells TIME that their study’s results say that “we can reprogram all the major fat stores in humans by intervening in this particular pathway.”
MIT’s announcement includes the news that the Prof. Kellis’ aims to translate their findings into obesity therapeutics — and AP reports that Kellis and his study’s co-author are seeking a patent related to the work.
As MIT News reports, obesity is one of the biggest public health challenges of the 21st century. Affecting more than 500 million people worldwide, obesity costs at least $200 billion each year in the United States alone, and contributes to potentially fatal disorders such as cardiovascular disease, type 2 diabetes, and cancer.
The team’s groundbreaking study, published online on Wednesday in the New England Journal of Medicine, analyzing the cellular circuitry underlying the strongest genetic association with obesity, has unveiled a new pathway that controls human metabolism by prompting our adipocytes, or fat cells, to store fat or burn it away.
“Obesity has traditionally been seen as the result of an imbalance between the amount of food we eat and how much we exercise, but this view ignores the contribution of genetics to each individual’s metabolism,” says Kellis, the study’s senior author, and a professor of computer science and a member of MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) and of the Broad Institute.
“Knowing the causal variant underlying the obesity association may allow somatic genome editing as a therapeutic avenue for individuals carrying the risk allele,” Kellis says. “But more importantly, the uncovered cellular circuits may allow us to dial a metabolic master switch for both risk and non-risk individuals, as a means to counter environmental, lifestyle, or genetic contributors to obesity.”
“By manipulating this new pathway, we could switch between energy storage and energy dissipation programs at both the cellular and the organismal level, providing new hope for a cure against obesity,” Kellis says.
The researchers are currently establishing collaborations in academia and industry to translate their findings into obesity therapeutics. They are also using their approach as a model to understand the circuitry of other disease-associated regions in the human genome.
The paper is a tour de force, according to Evan Rosen, a professor of medicine at Harvard Medical School who was not involved in the research.
“The researchers present a near-complete unveiling of how a genetic risk allele in a noncoding region of the genome really works,” Rosen says. “It’s really an extraordinary piece of science, and it provides a template for how we should be approaching these genetic variants in all disease areas.”
Obesity is one of the biggest public health challenges of the 21st century. But there may now be a new approach to prevent and even cure obesity, thanks to a study — led by researchers at MIT and Harvard Medical School — that has found a pathway that controls metabolism by prompting fat cells to store or burn fat. Read more at: news.mit.edu