Skinny" gene keeps mice lean, study finds

By Maggie Fox, Health and Science EditorTue Sep 4, 4:35 PM ET
A gene that keeps mice and fruit flies lean might offer a way to prevent obesity and diabetes in people, U.S. 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 Center 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 behavior 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.
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.
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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 in a telephone interview.
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."