In lab, fat mice slim down
Weight losss and maintenance achieved with cancer drugs

In a study published in the August 6 issue of the Proceedings of the National Academy of Sciences, researchers led by Maria Rupnick, MD, PhD, research associate in the Surgical Research Laboratories and a cardiologist at Brigham and Women’s Hospital, have shown that the growth of fat tissue can be prevented by controlling the blood vessels that feed it.

As anyone who’s ever put on some pounds over the holidays knows, fat tissue can grow and expand in ways that other tissues can’t. Since all tissue requires a blood supply, researchers surmised that the growth of fat tissue depends upon the formation of new blood vessels, a process known as angiogenesis. Researchers in the Surgical Research Laboratories have been learning how to control angiogenesis ever since Judah Folkman, MD, director of the labs, discovered 30 years ago that the process is central to the growth of cancerous tumors.

Rupnick and colleagues from MIT studied blood vessels in fat tissue using a strain of mice with severe obesity. When the obese mice were given drugs that prevent blood vessel growth (angiogenesis inhibitors), the blood vessels in the fat tissue regressed, reducing fat cells and causing the animals to shed weight. Blood vessels in other organs were not affected. The mice maintained their lower weight while receiving the drugs and regained the weight when the drugs were stopped. Normal mice, which have far less fat tissue, lost relatively little weight with angiogenesis inhibitors.

“The work is most consequential because it establishes that the principles of angiogenesis-dependent tumor growth can be extended to non-tumor tissues, as well,” says Rupnick.

Rupnick and her team did not set out to develop technology aimed at weight loss. They chose to study fat because it is a good example of a non-cancerous tissue that is able to grow bigger. While the possibility exists that angiogenesis inhibitors may someday be used to maintain or reduce weight in humans, Rupnick stressed that it is premature to make this claim.

“As a cardiologist, I appreciate that treating morbid obesity can significantly lower a patient’s risk for heart disease, high blood pressure, diabetes and other conditions,” says Rupnick. “However, it is important to keep in mind that, at this point, the studies have been conducted only in mice.”

Still, doctors are hopeful that Rupnick’s findings will lead to broader applications for angiogenesis inhibitors, achieving medical benefits beyond fighting cancer.—CM

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