Hormone signals the death of fat cells.
While the details remain obscure, the discovery of this cellular self-sacrifice may suggest new ways of treating obesity, says study coauthor Clifton A. Baile of the University of Georgia in Athens.
After finding several years ago that some strains of obese mice are deficient in either leptin production or the ability to recognize the hormone, investigators have rushed to understand leptin's roles in the human body. Leptin secreted by fat cells travels to the brain, where it seems to help regulate appetite and some aspects of the body's metabolism.
Obese rats injected with leptin, for example, eat less, burn more energy, and lose dramatic amounts of weight. Studies have also shown that leptin causes cells to shed or metabolize their fatty molecules (SN: 5/3/97, p. 271).
Prompted by colleague Hao Qian, Baile and his research group looked at whether leptin also induces fat cells to undergo apoptosis, an internal program culminating in suicide.
After injecting leptin into the brains of rats for several days, the scientists examined samples of the animals' fatty tissues. Cells committing suicide exhibit a characteristic fragmentation of their DNA. This apoptotic signature appears in the fat tissue of leptin-treated rats but not in their other tissues or in untreated rats, the investigators report in the February Endocrinology.
Other tests revealed that the leptin-treated rats experienced several times more apoptosis than the untreated rats. Moreover, when the scientists looked at fat tissue from leptin-treated rats, they saw additional signs of apoptotic cells.
The new work definitely "raises the notion that one mechanism by which leptin acts is to actually kill off fat cells rather than metabolically alter them," says Jeffrey S. Flier of Beth Israel Deaconess Medical Center in Boston.
Flier nonetheless remains skeptical that the body normally eliminates fat cells in this way. It's probably rare, he says, that leptin concentrations would be high in the brain but not in the blood.
Baile agrees but argues that this artificial situation may nevertheless have identified an unrecognized way in which the body can lose weight--the specific destruction of fat cells.
When applied directly to fat cells, leptin does not cause cell death. Baile suggests that the hormone tells the brain to induce suicide in fat cells. The brain may deliver this death sentence either by sending electric impulses through nerves connected directly to fat cells or by releasing an apoptosis-inducing protein into the blood.
Such a protein would be an obvious candidate for development as an antiobesity drug, says Baile. He and his colleagues are now investigating whether the blood-borne signal is tumor necrosis factor-alpha, a protein that other researchers have found can induce fat cells to commit suicide.