http://www.cnn.com/2004/TECH/science...eut/index.html

Study: Molecule 'vacuums' fat in mice



WASHINGTON (Reuters) -- A new approach being used to fight cancer may also help fight fat, U.S. researchers said Sunday.

They said blocking a certain protein seems to literally vacuum fat off mice.

When fat mice were injected with the new "fat-zapper" every day for a month, they all slimmed down to normal weight with no visible side-effects, the researchers reported in the June issue of Nature Medicine.

But they stressed the experiment is still in the very early stages and it affects a function found in virtually all cells -- meaning it has a high potential for serious side-effects.

"I am trying to un-hype this," said Dr. Wadih Arap of the M.D. Anderson Cancer Center in Houston, Texas, who led the research.

In cancer, a new class of drugs called angiogenesis inhibitors starve tumors by cutting off their blood supply.

Arap and colleagues have turned this approach against fat.

It makes sense, Arap argues -- fat cells grow and proliferate quickly just as cancer cells do. Like tumors, they build themselves a scaffold of tiny blood vessels called capillaries for sustenance.

Cancer drugs tackle different proteins involved in building blood vessels. Arap's team looked for a protein that might be found only in the blood vessels that feed fat cells.

They found one. Prohibitin is active on the surface of fat-feeding blood vessels. They also found a monoclonal antibody -- a synthetic immune system molecule -- that finds and attaches to prohibitin alone.

Reversing obesity
"If even a fraction of what we found in mice relates to human biology, then we are cautiously optimistic that there may be a new way to think about reversing obesity," said Renata Pasqualini, Arap's research partner and wife.

Arap's team made the monoclonal antibody lethal by attaching it to another protein fragment or peptide that causes apoptosis -- a natural programmed cell suicide.

Then they put normal mice on what they called a "cafeteria diet". "It is high in calories," Arap said in a telephone interview. The mice started out weighing just under an ounce, 20 to 25 grams, but more than doubled their weight on the diet.

Then they injected half the mice with the new fat-killing molecule. After daily injections for a month, the fat mice lost, on average, 30 percent of their body weight.

"The weight loss was also accompanied by a reversal of fatty liver and glucose intolerance," Arap said, describing two common complications of obesity. "They actually looked better. You could see them walk and so on."

They also tested aging mice, which tend to get fat. "They responded just the same. They looked a little thinner," he said.

Arap said his team saw no side-effects. "They didn't have any signs of being ill," he said. "All measures look improved. If they had a side-effect we couldn't detect it."

Arap's team did not measure how long their mice lived and they did not measure lean body mass to see if the mice lost healthy muscle tissue, too.

Next they plan to test baboons, which tend to put on weight much as humans do.

Arap noted that other research in which fat rodents have miraculously lost weight has not translated to humans. And prohibitin is found inside cells, which means that accidentally disrupting it there could cause severe side-effects.

"I think it will be a while before we know whether this will be duplicated in humans," he said.