Wednesday September 20 5:15 AM ET
Scientists Find New Obesity Gene
By EMMA ROSS, AP Medical Writer
JERUSALEM (AP) - Australian scientists have identified a new gene responsible for controlling appetite in humans - a discovery experts said could lead to the first gene-based drug to treat obesity and diabetes.
Greg Collier, a professor of microbiology at Deakin University in Melbourne, discovered the gene while researching diabetes in Israeli desert rats. The gene, which he called Beacon, cranks up the appetite and the rat version is identical to the human one.
The find, presented Tuesday at a conference of the European Society for the Study of Diabetes, is the third gene linked to obesity, after leptin and NPy.
However, Sir George Alberti, president-elect of the International Diabetes Federation, said a drug based on Beacon could be available sooner than one targeting the other two genes because the rat and human genes are a 100 percent match. This means drug research could proceed more quickly than normal because the results in rats would be more relevant to humans, he said.
``It is a very exciting development. It could be a very important step in the whole obesity, diabetes pathway,'' he said.
Collier and his 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 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.
They found an 81 percent match with the earthworm, said Dr. Paul Zimmet, professor of diabetes at Monash University in Caulfield, Australia, who participated in the research.
About 800 million years of evolution separate the earth worm from the Israeli sand rat, said Zimmet, adding that a gene which is preserved 81 percent over 800 million years of evolution must play an important role.
Collier then searched the libraries of human genetic information for anything that matched the rat gene sequence. He 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.
Collier 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.
Preliminary studies show the human gene is the same across various regions and ethnicities, Collier said.
The next step, Collier said, 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.
``It might for all we know be a bubble, but it looks really good next to Leptin and NPy because the animal is an exact model of human obesity and diabetes,'' Zimmet said.
The discovery of the gene, located on chromosome 19, is scheduled to be published in the journal Diabetes next month.