Study reveals an ancient gene for lean

Researchers have revealed an antiobesity gene that has apparently been keeping critters lean during times of plenty since ancient times. The gene, first discovered by another team in flies, also keeps worms and mice trim, according to the new report in the September issue of Cell Metabolism, a publication of Cell Press. If the gene works similarly in humans, the findings could lead to a new weapon against our burgeoning waistlines, according to the researchers.

Animals without a working copy of the gene, known as Adipose (Adp), become obese and resistant to insulin, while those with increased Adp activity in fat tissue become slimmer, the researchers found. Moreover, the gene’s “dose” seems to determine how slender an animal turns out to be.

“Maybe if you could affect this gene, even just a little bit, you might have a beneficial effect on fat,” said Jonathan Graff of the University of Texas Southwestern Medical Center, noting that people often become overweight very gradually—adding just one or two pounds a year. “After 30 years, that’s a lot.”

While worms and flies are routinely studied as models of human health and disease, that trend has been less true in fat biology, Graff said. That’s because unlike mammals, worms and flies store their fat in multifunctional cells rather than in dedicated fat cells known as adipocytes. However, those differences didn’t preclude the possibility that the animals might use similar genes to accomplish their fat storage goals, he added.

In the new study, Graff’s team found that worms lacking Adp activity became fat, although they appeared to be otherwise healthy and fertile. The researchers scoured the genetic database in search of related genes and found one with “tremendous” similarity in flies.

Indeed, another scientist, Winifred Doane, had found a naturally occurring strain of plump flies in Nigeria almost 50 years ago that carried a mutation in their Adp gene. The flies lived in a climate marked by cycles of famine, where they may have benefited from being highly efficient at fat storage, Doane had suggested.

To explore Adp’s function even further, Graff and his colleagues produced a strain of mutant flies like those that Doane had found years earlier. They found that the mutant flies were indeed fat and also had trouble getting around. Flies with only one copy of the Adp mutation fell somewhere in between the fat and normal flies, evidence that the gene’s effects are “dose dependent,” they reported.

Treatments that increased Adp in the insects’ fat tissue led them to lose weight, evidence that the gene operates within fat cells themselves. In mice that expressed the gene in fat-storing tissues, the same patterns emerged.

“We made mice that expressed Adp in fat-storing tissues, and lo and behold, what happened"” Graff said. “They were skinny—weighed less with markedly less fat—and their fat cells were smaller.” Smaller fat cells usually translate into better metabolic function, he said, including better blood sugar control.

“It’s a striking conservation of genes that restrain fat,” he said. While fat storage is an important mechanism for getting through lean times, “too much fat in times of plenty has deleterious consequences.”

The search for molecules underlying weight gain and poor blood sugar control “has taken on additional urgency due to the recent dramatic increase in obesity and diabetes,” Graff said. But in a modern world where many people have essentially unlimited access to food, it’s a wonder that even more people aren’t overweight, he added. If this gene plays a similar role in humans, “it may be that some people’s Adp works very well.”

Source: Cell Press

Related stories:

Study finds genes behind alcohol sensitivity in fruit flies
Some fruit flies can drink others under the table. Now, scientists at North Carolina State University have a few more genetic clues behind why some flies are more sensitive to alcohol than others. And the results might lead to more knowledge about alcoholism in humans.
'Skinny gene' does exist, researchers find
Researchers at UT Southwestern Medical Center have found that a single gene might control whether or not individuals tend to pile on fat, a discovery that may point to new ways to fight obesity and diabetes.
Leibniz Prize winners 2007 announced
The Deutsche Forschungsgemeinschaft (German Research Foundation, DFG) has announced the winners of its 2007 Gottfried Wilhelm Leibniz Prize. At its meeting on 7 December 2006, the DFG Joint Committee named ten scientists and academics — eight men and two women — as recipients of Germany’s most highly endowed research award. For the first time, the prize winners for 2007 will receive up to 2.5 million euros (previously: 1.55 million euros) and be able to use these funds flexibly over a period of seven years (previously: five years) to finance their research.
Single Molecule Makes Obese Mice Healthy
Researchers have used a single compound to increase the lifespan of obese mice, and found that the drug reversed nearly all of the changes in gene expression patterns found in mice on high calorie diets—some of which are associated with diabetes, heart disease, and other significant diseases related to obesity. The research, led by investigators at Harvard Medical School and the National Institute on Aging, is the first time that the small molecule resveratrol has been shown to offer survival benefits in a mammal. The study is reported in the November 1 advanced online edition of Nature.
African parasite makes component of fat differently from all other organisms
Studying the parasite that causes African sleeping sickness, scientists at Johns Hopkins have discovered a previously unknown way of making fatty acids, a component of fat and the outer layer of all cells. The find unveils more about the biology of this hard-to-kill parasite and could lead to a target for designing new drugs to fight the illness that infects a half-million people and kills 50,000 a year worldwide.
The body's own 'marijuana' is good for the skin
Scientists from Hungary, Germany and the U.K. have discovered that our own body not only makes chemical compounds similar to the active ingredient in marijuana (THC), but these play an important part in maintaining healthy skin. This finding on "endocannabinoids" just published online in, and scheduled for the October 2008 print issue of, The FASEB Journal could lead to new drugs that treat skin conditions ranging from acne to dry skin, and even skin-related tumors.
Small protein may have big role in making more bone and less fat
A small protein may have a big role in helping you make more bone and less fat, researchers say. "The pathways are parallel, and the idea is if you can somehow disrupt the fat production pathway, you will get more bone," says Dr. Xingming Shi, bone biologist at the Medical College of Georgia Institute of Molecular Medicine and Genetics.
Starvation hormone makes for small mice
Chronically high levels of a recently discovered starvation hormone markedly stunt the growth of mice, reveals a new study in the July issue of Cell Metabolism, a publication of Cell Press. The liver-produced hormone known as FGF21 does so by causing the mice to become resistant to growth hormone.

News discussion:

General Science news