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Back To Vidyya Another Obesity Causing Gene Discovered

Desert Rat Gene Identical To Gene Found In Humans - Gene Controls Some Appetite Centers

In a study to be published in the October issue of Diabetes, Australian researchers working with desert rats have discovered a human gene that experts say could lead to the first gene-based drug to treat obesity and diabetes.

A professor of microbiology at Deakin University in Melbourne, Australia uncovered the gene, which he refers to as Beacon, while researching diabetes in Israeli desert rats. The gene boosts appetite and the rat version is identical to the human one.

Beacon is the third human obesity gene to be discovered, after leptin and NPy, but Sir George Alberti, president of the Royal College of Physicians in London and president-elect of the International Diabetes Federation, said a drug based on it could be available sooner than ones targeting the other two genes because the code of the rat and human Beacon genes are a 100 percent match.

Experiments with drugs to interfere with the Beacon gene could progress more quickly and easily than drug research normally does because in this case the results in rats would be more relevant to humans, he said.

The Australian team took sand rats from the Negev desert in Israel to a laboratory in Melbourne for diabetes research. On their cactus diet in the desert, the rats were lean and healthy. But placed in a Western environment, where rat chow was abundant, some of them ate a lot, got fat and developed diabetes; others ate reasonable amounts and remained lean.

This prompted the researchers to look for genetic differences. They removed the rats' brains, examined every gene to find whether any were more active in the fat rats and came up with the Beacon gene.

Genes direct the formation, or expression, of proteins that a cell uses to function, repair or defend itself, and to divide. In the obese rats, the Beacon gene was working in overdrive, forming too much appetite-stimulating protein.

Once they had deciphered the sequence, or unique code, of the rat gene, the scientists searched for a match on an Internet gene databank.

"There was only one match. That was a fragment of DNA from the earthworm," said Dr. Paul Zimmet, professor of diabetes at Monash University in Caulfield, Australia, who participated in the research. "It was 81 percent the same as the earth worm DNA."

Then the researchers checked the libraries of human genetic information for anything that matched the rat gene sequence and found the identical gene sequence in human DNA.

The Beacon gene produces a protein that stimulates the appetite. NPy does the same thing, whereas leptin switches off the appetite. In some obese people, the body does not respond to leptin.

Collins then produced the protein from the human Beacon gene and injected it into the brains of lean rats with normal behavior of the gene. They gained about 5 percent of their own body weight in 7 days.

When he injected protein from both the Beacon and NPy human genes, the rats ate even more and ballooned by 10 percent in a week, going from 200 grams to 220 grams in weight.

The next step is to subject the protein to hundreds of chemicals to see if any can block its action.

The hope is that a drug could fix the problem if the gene is pumping out too much of the protein. The proposed drugs would then be tested on rats before being given to humans.

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Editor: Susan K. Boyer, RN
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