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August 5, 2002

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Fat Tissue Can Be Controlled By the Blood Vessels That Feed It

Weight loss and and maintenance in mice achieved with angiogenesis inhibitors

BOSTON - 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, cardiologist at Brigham and Women's Hospital and research associate in the Surgical Research Laboratories at Children's Hospital Boston, have shown that the growth of fat tissue can be prevented by controlling the blood vessels that feed it.

Rupnick and her colleagues at Children's Hospital and the Massachusetts Institute of Technology determined that fat tissue growth depends upon the formation of new blood vessels (angiogenesis). Unlike most other organs that do not change in size, fat tissue can grow and expand greatly, even in adults. The authors surmised that, like tumors, fat tissue would require new blood vessels to allow such growth to occur.

The investigators studied blood vessels in fat tissue using a strain of mice that develops severe obesity. When the obese mice were given angiogenesis inhibitors, drugs that prevent blood vessel growth, the blood vessels in the fat tissue regressed. This promoted the reduction of fat cells and the animals lost the excess 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 pioneered by Dr. Judah Folkman can be extended to non-tumor tissues as well,'' said Rupnick. ''However, I am often asked: 'Could this science be used to develop clinical applications to fight obesity?'''

Rupnick and her team did not set out to develop technology aimed at weight loss. The scientists chose to study fat because it is an example of a non-cancerous tissue that is especially able to grow. 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,'' Rupnick said. ''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 the drugs that control blood vessels, achieving medical benefits beyond fighting cancer.

BWH is a 716-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare System, an integrated health care delivery network. Internationally recognized as a leading academic health care institution, BWH is committed to excellence in patient care, medical research, and the training and education of health care professionals. The hospital's preeminence in all aspects of clinical care is coupled with its strength in medical research. A leading recipient of research grants from the National Institutes of Health, BWH conducts internationally acclaimed clinical, basic and epidemiological studies.

Children's Hospital Boston is the nation's premier pediatric medical center. Founded in 1869 as a 20-bed hospital for children, today it is a 300-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's Hospital is the primary pediatric teaching hospital for Harvard Medical School, home to the world's leading pediatric research enterprise, and the largest provider of health care to the children of Massachusetts. For more information about the hospital visit: www.childrenshospital.org.