Scientists say they have discovered how a gene linked to obesity is causing people to gain too much weight.
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To identify the cell types in which the FTO obesity-risk region might exert its effects, the researchers analyzed information from the Roadmap Epigenomics project, which assesses chemical or “epigenetic” modifications within chromosomes that switch genes on or off. The project’s data revealed that the strongest epigenetic signal was found in “preadipocyte” cells, the progenitor cells that go on to become fat cells. 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.
“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”, said Manolis Kellis, senior author of the new study, in a news release.
Dr. Clifford Rosen, scientist from the Maine Medical Center Research Institute and associate editor for the New England Journal of Medicine, gave a statement saying that the new findings are “a big deal”. While FTO has been known to affect obesity, researchers have not previously been able to find the mechanism that explains how genetic differences can lead to obesity. Furthermore, the FTO gene turns on two other genes which are responsible for preventing fat from burning, meaning even those who exercise may not be able to lose weight simply because they have that particular gene. “You now have a pathway for drugs that can make those fat cells work differently”.
Researchers used a new technology called the Crispr/Cas9 system to edit the DNA code and fix the sequence in mice and human cells.
The teams have discovered that the gene triggers two other genes that stop fat being burned up as heat.
Researchers have known since 2007 that the fat gene FTO was related to obesity, but they didn’t know how. Disruption also resulted in a cell-autonomous developmental shift from energy-dissipating beige adipocytes to energy-storing white adipocytes, with a reduction in mitochondrial thermogenesis and increase in lipid storage. “We now have the circuits, and can turn the knob to energy storage or energy dissipation”, he says. If that’s the case, they may have an explantion for why some people are more likely to become obese.
If future studies are successful, the method could offer a novel way to cure obesity, a major public health problem that experts say affects some 500 million people around the world and can lead to cardiovascular disease, Type 2 diabetes and cancer.
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“The researchers present a near-complete unveiling of how a genetic risk allele in a noncoding region of the genome really works”, Rosen told MIT. But the work may point to a new way to control body fat.
