'Skinny' gene discovered
2007-09-05 07:18
Washington - A gene that keeps mice
and fruit flies lean might offer a way to prevent obesity and
diabetes in people, US researchers said on Tuesday.
The gene, discovered more than 50 years ago in fruit flies,
makes mice fat when tweaked one way and thin when manipulated
another way, the researchers reported.
That suggests it would work this way in humans, because
mice and people are both mammals, the team at the University of
Texas Southwestern Medical Centre reported.
"If you turn up its function, you get skinny, and if you
turn down its function, you get fat," Dr Jonathan Graff, who
directed the research, said in a telephone interview.
"This is a skinny gene. It's an anti-thrifty gene."
For years, researchers seeking to explain why people are
prone to get fat have used the "thrifty gene" hypothesis. Early
humans who survived famine after famine were those who could
easily store a layer of fat for the lean times.
While obesity is likely to be caused by a variety of genes
and their interactions with behaviour and the environment, this
one is a good candidate for study, Graff and colleagues report
in the journal Cell Metabolism.
The gene, called adp for adipose, was discovered by
Winifred Doane, while she was studying infertility in fruit
flies as a graduate student at Yale University.
Doane, now a professor emeritus of zoology at Arizona State
University, stressed the flies by starving them and putting
them in a desiccator to simulate extreme conditions. Those that
lacked a working copy of the adp gene survived, despite
starvation and dry conditions.
Do these genes make you look fat?
Jae Myoung Suh, a graduate student working on his PhD in
Graff's lab, used Doane's work as the basis of an experiment in
mice.
Finding that it works in the same way in mice and fruit
flies is important because it means the gene is conserved, or
has evolved from "lower" to "higher" animals.
"It was always my dream that the drosophila (fruit fly)
adipose gene would turn out to be a model for controlling
obesity and type 2 diabetes. It looks like it is starting in
that direction now," Doane said.
Doane said the gene appears to be a regulatory gene,
meaning it controls the activity of other genes.
Graff and other experts say one place to start looking for
humans who have mutant versions of the gene would be Pima
Indians from the southwestern United States and Australian
aborigines, both of whom have high rates of type-2 diabetes and
obesity when they begin living Western lifestyles.
"Even if people don't have abnormalities in this gene, if
you had a drug that could work on this, you could treat
people," Graff said.
In humans, adp is in a region of the genome that is already
linked to obesity and diabetes, Graff said.
And it is not an all-or-nothing gene, at least not in mice
tested in the lab. "This is a volume control - not on and off.
As you get less and less function of protein, you get fatter
and fatter, and as you get more and more, you get skinnier and
skinner," Graff said.
"People who want to fit in their jeans might someday be
able to overcome their genes."