By Denise H. Horton
A team of UGA scientists has determined that the hormone leptin causes the programmed death of fat cells rather than simply reducing them in size.
Their discovery helps explain why rats injected with leptin stay thin long after treatment has stopped and could play a significant role in the use of leptin for the treatment of obesity, according to Clifton A. Baile, distinguished professor of foods and nutrition and animal science.
The scientists presented their results in San Diego last month at the Annual Conference on Apoptosis.
Research on leptin has exploded in the two years since it was 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 in research on the use of leptin to treat obesity and it's expected that leptin-based medication will be available within five years.
The UGA team's contribution to the understanding of leptin begins with the arrival of Hao Qian, a post-doctoral fellow who came to UGA a year ago after spending several months researching apoptosis--programmed death--of cells in the spinal cord following spinal-cord injuries.
In general, apoptosis is a routine process that occurs in most tissues. It causes leaves to fall from the trees in autumn; it is 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 introduced in scientific literature in 1972; however, extensive research on the role it plays in a variety of organisms didn't begin until 1992, so Qian's hypothesis was quite novel.
"When Hao first suggested that the fat cells' reaction to leptin looked like apoptosis, we didn't think he was right," Baile says.
However, the team developed a series of experiments to test the hypothesis. The scientists injected one group of rats with leptin, placed a second group on a low-calorie diet, and gave normal amounts of food and no leptin to a third group.
The DNA of the fat cells of the leptin-treated rats clearly showed apoptosis. The DNA of the rats on the low-calorie diet and of the control group, in contrast, failed to show any signs of apoptosis.
"The only cells affected in the leptin-treated rats were the fat cells," Baile says. "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 explains. "However, with leptin, that's not the case."
Baile says it takes weeks for leptin-treated rats to recover the fat they have lost.
"We have had trouble finding any fat cells in rats within five days of treatment," he says.
