NEW YORK (Reuters Health) - Depriving fatty tissue of its nutrient-rich blood supply can stop obese mice from continuing to gain weight--and even, in some cases, help them lose weight by reducing existing fat tissue, new study findings show.

Investigators headed by Dr. Maria Rupnick of Brigham and Women's Hospital and Children's Hospital in Boston successfully trimmed down obese mice by giving them drugs that inhibited the formation of new blood vessels, a process known as angiogenesis.

For years, researchers have been investigating how to starve growing tumors by inhibiting angiogenesis, and these findings demonstrate that a similar approach may be possible in non-cancerous tissue as well, Rupnick told Reuters Health.

However, she cautioned, zapping fat growth with angiogenesis inhibitors has only been demonstrated in mice, and researchers have a long way to go before they can consider using this approach to treat obesity in humans.

"If humans respond similarly to mice--and that's a gigantic if--then it's possible" that the drugs could treat obesity in humans, Rupnik said.

"Finding a way to treat obesity was never our intention," she added. "It's really premature to say that now. But I don't know--it may."

Most organs do not grow much once the body reaches adult size. But in those who eat more fat and calories than their bodies can process, fat tissue will expand over time. And for fat tissue to survive and grow, it must have a blood supply.

Researchers know that tumors "recruit" blood vessels to their cause, then activate proteins that spur the growth of new vessels. As such, Rupnick and her team guessed that as the mice gained weight, the expanding fat tissue would undergo angiogenesis, as well.

During the study, Rupnick and her colleagues--including Dr. Judah Folkman of Children's Hospital, one of the early investigators into the potential of angiogenesis inhibitors to halt tumor growth--administered various angiogenesis inhibitors to obese mice.

Reporting in the August 6 issue of Proceedings of the National Academy of Sciences, the authors found that the drugs successfully slowed or stopped the growth of fat tissue and, in some cases, actually caused the mice to lose weight.

In an interview with Reuters Health, Rupnick noted that some mice lost around 30% of their original body weight.

She explained that she and her team did not try to determine which drug or dosage worked best, but noted that different drugs produced different effects in the obese mice.

"These drugs may stop new blood vessel growth, but they may do it in different ways," she suggested.

And obese mice that lost weight after receiving angiogenesis inhibitors underwent some sort of "metabolic adaptation," decreasing the amount of food they ate, Rupnick said--almost as if their bodies realized how much food they now had room to take in.

The reduction in body fat induced by the drugs was not permanent, Rupnick added. Once the researchers stopped administering treatment to the mice who lost weight, the animals gained the weight back. However, if treatment was restarted, she noted, the mice were able to shed excess pounds once more.

Rupnick said this finding indicates that, in some cases, obesity may be "something you need to treat for a lifetime."

SOURCE: Proceedings of the National Academy of Sciences 2002;99:10730-10735.

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