Leptin Sparks Blood Vessel Growth

The obesity hormone leptin and blood vessel growth, called angiogenesis, have both made headlines. Now, in a curious twist, researchers have brought the two stars together: They report in today's Science that leptin triggers angiogenesis in experimental animals. Scientists suspect leptin may contribute to the formation of the new blood vessels needed when fat increases in volume. It may also spur blood vessel growth in healing wounds.

The work grew out of a chance discovery by biochemist M. Rocío Sierra-Honigmann of Yale University. She was helping her husband, who had engineered cultured cells to make the leptin receptor--which until then had been found mainly in the brain. Sierra-Honigmann was using antibodies to confirm that the cells actually contained the receptor. As a control for the antibody test, she used endothelial cells--the type of cells that form blood vessels. To her surprise, those cells scored positive, indicating that they naturally contain the leptin receptor. "It kept me awake at night," says Sierra-Honigmann. "If I were an endothelial cell, why would I want leptin receptors?"

To find out, Sierra-Honigmann enlisted the help of several angiogenesis researchers. They determined that leptin causes cultured endothelial cells to aggregate, forming tubes that resemble the early stages of blood vessels. Leptin even spurred new blood vessels to form in the corneas of rats, the "gold standard" for an angiogenic molecule.

"No one would have thought that leptin has anything to do with angiogenesis. This is a paper that is going to change people's thinking," says angiogenesis pioneer Judah Folkman of Harvard Medical School in Boston. Leptin may, he suggests, "drive the blood vessels to match the fat." It does not appear to be essential for that job, however, because the copious fat tissue in mutant mice that completely lack leptin manages to recruit an adequate blood supply.

Leptin may have other roles as well. For example, wound healing depends on blood-vessel growth, and researchers had noted that healing is slow in leptin-deficient mice. In preliminary experiments, Sierra-Honigmann and her colleagues have now shown that extra leptin can speed healing. In addition, she says, the slow-healing wounds of leptin-mutant mice "heal like normal wounds" when treated topically with leptin.