October 3 , 2003

Blood vessel development interacts with fat formation

The physiological processes of angiogenesis, the growth of new blood cells, and adipogenesis, the development and growth of fat cells, appear so closely interwoven that interfering with one process also halts the other. These findings from MGH researchers — which could help to solve problems ranging from cancer to obesity to the development of replacement organs — were published online Oct. 2 by the journal Circulation Research.

"It really looks like angiogenesis and adipogenesis are joined at the hip,"says Rakesh K. Jain, PhD, director of the Steele Laboratory for Tumor Biology at the MGH, and senior author of the study. "These findings are helping us understand just how closely these processes work together and identify new ways of controlling these functions to meet important medical challenges."

The research team first implanted normal preadipocytes (fat cell precursors) into chambers beneath the skin of immune-deficient mice, and as expected the cells differentiated into mature fat cells. Blood vessels that developed to supply the growing tissue also formed efficient, organized networks, something that rarely happens outside of natural growth conditions. To block fat cell differentiation, the researchers introduced an inactive form of a protein required for fat cells to mature. Not only did the affected implants neither grow nor differentiate into mature fat cells, but there also was no blood vessel development. Similarly, introduction of an antibody against a protein key to angiogenesis prevented blood vessel development in the implants and also kept the fat cell precursors from maturing.

These findings could have a wide range of medical applications. Anti-angiogenesis compounds already are being evaluated as cancer-fighters and now may be useful in combating obesity. The observation that blood vessels growing in response to adipogenesis form organized networks might help with efforts to grow new organs and tissues, as developing a circulatory system is a key challenge in tissue engineering.
Dai Fukumura, MD, PhD; Akira Ushiyama, PhD, and Dan Duda, DMD, PhD, of the Steele Laboratory are co-first authors of the paper. Other MGH authors are Lei Xu, MD, PhD, Joshua Tam, BS, and Igor Garkavtsev, MD, PhD.