A team of University of Georgia researchers is the first to find that the hormone leptin causes the programmed death of fat cells rather than simply reducing their size.
The discovery helps explain why rats injected with leptin stay thin long after treatment has stopped. It could play a significant role in using leptin to treat obesity, said Clifton Baile, a UGA professor of foods and nutrition and animal science.
Research on leptin has exploded in the two years since it was first discovered by Rockefeller University researchers. The hormone is produced by the body's fat cells and travels through the blood stream to the brain. Animals treated with leptin eat less, lose weight and expend energy at a higher rate.
Pharmaceutical companies have invested hundreds of millions of dollars researching the use of leptin to treat obesity. Leptin-based medication is expected to be available within five years.
The UGA team's findings about leptin's effect on fat cells began after Hao Qian (pronounced Hall Chin), joined the UGA faculty a year ago. Qian spent several months researching apoptosis (programmed death) of spinal-cord cells following injuries.
In general, apoptosis is a routine process that occurs in most tissues. It's what causes leaves to fall from trees in autumn. It's also how the body eliminates diseased or unnecessary cells, such as a mother's milk-secreting mammary cells after a baby is weaned.
Apoptosis was first revealed in 1972. However, extensive research on the role it plays in a variety of organisms didn't begin until 1992. That explains why Qian's hypothesis about leptin's role in the destruction of fat cells was so novel.
"When Hao first suggested that the fat cells' reaction to leptin looked like apoptosis, we didn't think he was right," Baile said. However, the team developed a series of experiments to test the hypothesis.
The UGA scientists injected one group of rats with leptin, placed a second group on a low-calorie diet and gave a third, untreated, group normal amounts of food.
In comparing the DNA of the rats' fat cells, the cells of the leptin-treated rats clearly showed apoptosis. But the rats in the low-calorie diet and control groups showed no signs of it.
"The only cells affected in the leptin-treated rats were the fat cells," Baile said. "Cells in the liver, kidney and heart, as well as both smooth and skeletal muscle were not affected. This was true in male and female rats, young rats and older rats.
"A problem with most treatments for obesity is that once the treatment is stopped, the individual begins gaining weight almost immediately," Baile said. "However, with leptin, that's not the case."
Baile said it takes weeks for the leptin-treated rats to recover the fat they lose. "We've had trouble finding any fat cells in rats within five days of treatment," he said.
The scientists presented their results Oct. 27-28 in San Diego at the Annual Conference on Apoptosis. They also presented some of the research at a September workshop sponsored by the National Institutes of Health that focused on the brain and fat cells. The research will appear in the scientific journal, Endocrinology, later this year.