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MIT, Harvard find 'master switch' behind obesity
Doctors may have found a way to override the
body’s evolutionary habit of storing fat with a discovery of a master
switch for the body’s metabolism.
According to a study published Wednesday in the New England Journal of Medicine, researchers from the Massachusetts Institute of Technology and Harvard Medical School discovered a new genetic pathway that controls human metabolism by prompting fat cells to store or burn away fat.
“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 senior
author Manolis Kellis,
a professor of computer science and a member of MIT’s Computer Science
and Artificial Intelligence Laboratory and of the Broad Institute, in a
release.
Until now.
Previous research had shown there was a strong association with obesity
in the gene region known as FTO. Researchers started there,
experimenting with more than 100 tissues and cell types, changing the
genomic controls within that region to see if fat storage could be
programmed independently of the brain.
Once researchers
discovered evidence that there was a switchboard, researchers looked at
fat tissue from Europeans with differing versions of the region,
finding that those at risk for obesity had switchboards that turned on
two distant genes — IRX3 and IRX5.
Further research
into these genes showed that they act as master controllers of how fat
cells either burn fat as release the energy as heat, or store it.
The discovery
ultimately comes down to one letter nucleotide difference in these
genes, which turns on these genes and ultimately turns off the body’s
way of burning fat, leading to storage.
Changes in that one nucleotide changed the way the genes functioned, and made the cells burn energy instead of storing it.
“Knowing the
causal variant underlying the obesity association may allow somatic
genome editing as a therapeutic avenue for individuals carrying the risk
allele,” Kellis said. “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.”
Researchers
proved their findings in mice, by reprogramming the genes and finding
that there was dramatic changes in body weight and fat storage, as well
as a complete resistance to a high-fat diet.
“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 said.
The discovery is
a promising start to ultimately finding a therapy for those who have
the genetic code triggering fat storage. Researchers said they are
partnering with other academics and industry partners to create obesity
therapeutics, and are also using the approach to understand the
circuitry of how other diseases might be tied into the human genome.
