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.
