Protein may offer clue to obesity, diabetes
Protein may offer clue to obesity, diabetes - study
Fri Apr 19, 6:22 PM ET
By Maggie Fox, Health and Science Correspondent
WASHINGTON (Reuters) - A protein that affects the body's ability to handle fat and sugar might offer a way to treat obesity and diabetes, if a way can be found to block it, scientists reported on Friday.
Mice genetically engineered to lack the protein can eat a high-fat diet and stay lean, the researchers report in this week's issue of the journal Developmental Cell.
If a way can be found to block this protein in humans, it may -- and the researchers stress the word may -- be a way to treat or prevent diabetes and obesity, they said.
"If you eat the same amount of food it will make you gain less weight," Dr. Benjamin Neel, of Harvard University and director of the cancer biology program at Beth Israel Deaconess Medical Center, said in a telephone interview.
"I want it too," he joked.
The protein, called PTP1B for protein tyrosine phosphatase 1B, joins a list of proteins and enzymes that in mice are associated with obesity. Many different small biotech firms and large pharmaceutical companies are pursuing them as potential diet pills.
One-quarter of Americans are obese and 60 percent are overweight, so the market potential is considerable.
Neel and colleagues genetically engineered mice that lack the PTP1B protein. The protein acts both on the hormone leptin, which is secreted by fat cells and strongly linked to obesity, and on insulin, they found.
The mice that lacked PTP1B, even those missing just one of their two copies of the gene that controls production of the protein, were hypersensitive to insulin.
"What was unanticipated, however, was that the mice were surprisingly lean," Neel said.
It seems that not having the gene increases the body's sensitivity to insulin and leptin, meaning the two hormones work more efficiently in smaller amounts. The result was a revved-up metabolism.
MICE LOOKED LIKE HIGHLY TRAINED ATHLETES
"A PTP1B knockout mouse has some of the characteristics of a highly trained athlete to the extent that they have increased energy expenditure," Neel said.
He hopes to develop a drug -- hopefully a pill -- that could block the effects of the PTP1B protein in people.
Obese people have too much leptin. In normal amounts, leptin can reduce appetite, but it appears that years of overeating causes the body to stop responding to the hormone.
There is a similar effect in insulin resistance, which precedes diabetes, and in type-2 diabetes, which affects 15 million Americans.
Blocking PTP1B just might be able to reverse these two effects, Neel hopes.
Neel is so hopeful that he has joined the board of a company called Ceptyr, a small biotech headquartered in Bothell, Washington that hopes to capitalize on the kind of work he is doing.
In this study Neel's team worked with Millennium Pharmaceuticals, and Ceptyr works with other big drug companies, such as Eli Lilly and Co.
There are other proteins that may have similar effects, if they work in people as they do in mice. Last year a team at the Whitehead Institute at the Massachusetts Institute of Technology (news - web sites) in Boston identified one called adipocyte complement-related protein (Acrp30), made by fat cells.
A team at GlaxoSmithKline and Cambridge University in Britain are working on one called Uncoupling Protein 3 (UCP3) that increases mouse metabolism.
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