ATHENS, Ga. -- A team of researchers at the University of Georgia are the first to determine 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 at UGA.
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 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 findings about leptin's effect on fat cells began after the arrival of Dr. Hao Qian (pronounced Hall Chin), a post-doctoral fellow who joined 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 is what causes leaves to fall from the trees in autumn and 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 the scientific literature in 1972; however, extensive research on the role it plays in a variety of organisms didn't begin until 1992, which 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.
In their research, the UGA scientists injected one group of rats with leptin, a second group was placed on a low-calorie diet, while a third was given normal amounts of food and not treated with leptin.
In comparing the DNA of the fat cells of rats treated with leptin and the control groups, the fat cells of the leptin-treated rats clearly showed apoptosis. The DNA of the rats on the low-calorie diet and the control group failed to show any signs of apoptosis.
"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 explained. "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 have had trouble finding any fat cells in rats within five days of treatment," he said.
The scientists will present their results Oct. 27-28 in San Diego at the Annual Conference on Apoptosis. Some of the research also was presented at a September workshop sponsored by the National Institutes of Health that focused on the brain and fat cells.
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