Research Keeps Diet Pill Dream Alive
Molecular action of fat-fighting protein leptin revealed
MONDAY, Feb. 9, 2004 (HealthDayNews) -- Work on the molecular level with the fat-fighting protein leptin has revived hopes for a simple diet pill that would shed pounds effortlessly, researchers report.
The key finding is that leptin acts differently in cells of fat people than in those of thin people, says Dr. Roger Unger, director of the Touchstone Center for Diabetes Research at the University of Texas Southwestern Medical Center and leader of a group reporting its work in this week's issue of the Proceedings of the National Academy of Sciences.
"In skinny people, leptin causes fat to burn up," Unger says. "But nothing of the sort happens in a fat person's fat cell. When a person gets fat, his fat cells have resistance to the action of [their] own leptin. If the fat cells were no longer resistant, they would burn up fat the way they do in a normal person."
It's a long way from that finding to a magic diet pill, Unger acknowledges. "But this is the first step in understanding how a fat cell can prevent the fat-burning action of its own leptin."
Unger says his group has "a lot of ideas" about how to make leptin do its job in overweight people and "we are working on them now." He says he can't give further details until the work is ready for publication.
Leptin leapt into the headlines in 2001, when it was shown to be a protein that promoted the destruction of fat. But hopes faded when human trials showed leptin treatment did nothing to promote weight loss.
The Texas research provides a new target for treatment, Unger says: first identify the barrier that prevents leptin from doing its work in a fat person's fat cell, then break down that barrier.
The latest work was done with normal-weight mice. When they were given injections of leptin, the cells that normally store fat suddenly became fat-burning cells. The activity of their mitochondria, the principal energy-processing units of the cell, increased substantially, so the mice lost a lot of weight in just two weeks.
"What we would like is to be able to do the same thing in a fat person," Unger says. "So far, the problem seems to be resistance that a fat cell has against its own leptin."
That resistance is due to a basic defense mechanism built up over the eons when food was scarce, he says "The simple purpose of a fat cell is to get fat," Unger says. "That is the only way you can survive a famine. To store that fat, the cell has to be impervious to the effect of leptin."
When food becomes abundant, as it has in American society, that defense mechanism leads to obesity, Unger says. Now the research challenge is to alter the defense mechanism on the cellular level.
Meanwhile, Unger says, "There is a better way than a pill to lose weight: Don't eat so much."
Another leptin researcher, Dr. Michael Rosenbaum, an associate clinical professor of clinical pediatrics and medicine at Columbia Presbyterian Medical Center in New York City, urges caution about the finding.
"This is a very interesting study in terms of understanding the basic physiology of leptin," Rosenbaum says. "But the levels of leptin induced in the mice were well above normal physiological levels, so the applicability to weight loss in humans is uncertain."
"I don't want people to think that getting injections of leptin will lead to weight loss," he says. "It isn't going to happen."
A review of leptin and other molecules involved in obesity can be found at the Duke Weight Loss Surgery Center. Get an overview on obesity and overweight from the National Center for Chronic Disease Prevention and Health Promotion.