Obesity hormone tackles wound healing

In 1995, the media hailed the newly discovered protein leptin as the “obesity hormone” because it seemed to regulate the amount of fat stored by a body. While leptin remains an unproven weight-loss treatment (SN: 7/18/98, p. 43), scientists have found that the hormone may have many additional roles.

Leptin seems to play a part in immunity, puberty, reproduction, and, according to a study in the January Endocrinology, wound healing. Investigators at Amgen in Thousand Oaks, Calif., the company developing leptin for commercial purposes, report that injecting the hormone into mice lacking it significantly speeds the rodents’ ability to mend skin wounds. Applying leptin directly to a wound also accelerates its healing, the Amgen team reports.

Mice without a functioning gene for leptin become obese and develop diabetes. While trying to correct these problems by implanting leptin-releasing pumps under the skin of the animals, the Amgen group noticed something unexpected. “The wounds that surrounded the minipumps appeared to heal faster in leptin-treated animals,” recalls Dimitry M. Danilenko.

This observation raised the possibility that leptin could correct a dangerous complication of diabetes. “All aspects of wound closure are impaired or slowed in diabetic animals and in diabetic people. Lots of wounds just never heal,” notes Danilenko. “It’s a major problem.”

The investigators quickly began testing leptin specifically for its effects on healing. They applied the hormone directly to wounds, for example, to separate its local healing effect from a general improvement of metabolism after injection.

“There does appear to be, in addition to the systemic benefit, some direct local effect. As of yet, we don’t know the mechanism,” says Danilenko.

The Amgen team has found that cells in wounded skin, particularly those around blood vessels, make the cell-surface proteins that bind leptin and initiate its effects. Since formation of new blood vessels is an important facet of wound healing, the researchers tested whether leptin triggered this phenomenon, known as angiogenesis. They didn’t see such a response.

That result contrasts with a 1998 report by M. Rocío Sierra-Honigmann of Yale University, in which she and her colleagues describe angiogenesis triggered by leptin. They also observed, but have not yet reported, that leptin speeds healing in mice lacking the hormone.

Arguing that the Amgen scientists’ assay was unorthodox, Sierra-Honigmann asserts that angiogenesis largely accounts for the hormone’s healing properties. “I think angiogenesis is a central component of why they saw what they saw,” she says.

Would leptin enhance wound healing in normal mice? Danilenko says that Amgen’s data suggest a subtle boost but don’t prove it. Sierra-Honigmann, however, hints at better results in her as-yet-unpublished studies. Leptin and wound healing will make a “fascinating story,” she predicts.