To block fat-cell differentiation, the researchers implanted mice with preadipocytes that had an inactivated form of a protein required for fat cells to mature. Not only did the implants neither grow nor differentiate into mature fat cells, but there also was virtually no blood vessel development. Similarly, introduction of an antibody against a protein key to angiogenesis both prevented blood vessel development in the implants and also kept the fat cell precursors from maturing.
"These processes now appear to be coupled at very fundamental levels," Jain says. "And we are starting to identify the proteins involved and the stages at which they are active." Jain is the A. Werk Cook Professor of Radiation Oncology at Harvard Medical School.
Better understanding of the interaction between angiogenesis and adipogenesis and the development of ways to control and direct the processes could have a wide range of medical applications. Anti-angiogenesis compounds are already being evaluated as cancer-fighters, and the current results suggest they may be useful in combating obesity as well. The observation that blood vessels growing in response to adipogenesis form organized networks in contrast to the inefficient networks that develop in and around tumors might help with efforts to grow new organs and tissues, since the development of a circulatory system is a key challenge in the field of tissue engineering.
Fukumura, Duda and Ushiyama who is now with the National Institute of Public Health in Tokyo are co-first authors of the Circulation Research paper; other co-authors are Lei Xu, MD, PhD, Joshua Tam, BS, and Igor Garkavtsev, MD, PhD, of the Steele Lab at MGH, and Krishna Chatterjee, PhD, of the University of Cambridge, England. The study was supported by grants from the
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
2-Oct-2003