The Role of Leptin in Weight Loss

How can three family members slim down to half their body weight without even trying? With the help of an appetite control hormone called leptin, new research suggests.

Leptin, from the Greek "leptos" meaning thin, strives to live up to its name. The hunger hormone "has far-reaching physiological effects on both food intake and energy expenditure," says Dr. Steven Heymsfield, a professor of medicine at Columbia University in New York City.

Manufactured in the fat cells, leptin tells the brain whether the body has sufficient energy stores, or fat. The hormone sends satiety signals to the hypothalmus — the brain's eating control center — and tells us when we can stop eating, explains Dr. Julio Licinio, a professor of psychiatry and medicine at the University of California Los Angeles School of Medicine.

Everyone possesses leptin. Everyone except for Bayrum Donsek, Elif Fakili, and Zeynep Fakili. These three cousins from Turkey are the only known adults in the world to possess the genetic mutation that renders them leptin-deficient — and the consequences have been devastating.

In the absence of leptin, the brain never receives the message that the body has sufficient food, believing it to be in a constant state of starvation. For this reason, the Turkish family members have demonstrated voracious appetites, eating and eating themselves up to weights ranging from 235 pounds to more than 300 pounds, yet never feeling full.

Licinio flew the relatives from their isolated village to the University of California Los Angeles to participate in clinical trials funded by the National Institutes of Health. Everyday for the past 10 months, the cousins have received leptin injections while researchers have tracked every system in their bodies to record the effects of the hormone injections.

The results have been dramatic. So dramatic that the same individuals who required two seats each for their journey to America will soon return home in the regular one seat each.

The researchers did not instruct the subjects to eat more or less of anything, but because leptin affects appetite, explains Licino, the subjects' spontaneously began to feel much less hungry.

In addition, leptin stimulates physical activity, so their activity levels increased as well, continues Licinio. They began to slowly lose weight, and over time, the weight just kept dropping off — half of it gone in less than one year.

The Perfect Subjects

When researchers at Rockefeller University in 1995 injected fat mice with leptin, they became miraculously skinny. The discovery of leptin, it was believed, was the magic bullet, the entry to weight loss nirvana.

Except to every dieter's dismay, it didn't quite work the same way in humans as it had in animals.

This is because most people already have varying degrees of leptin. "Many hormones like leptin, when given in excess, have no discernible effect on the body, so it is hard to tell what the hormone really does," Licinio told ABCNEWS correspondent, Dr. Nancy Snyderman.

The only way to unlock the mystery of leptin and its role in weight control was to start from scratch, and find people who had no leptin at all. The Turkish cousins were the medical version of hitting the jackpot. They were the ideal research subjects.

"These patients, because they have no leptin of their own, have allowed us to see the real effects of the hormone when it is given," says Licinio.

The absence of leptin is an extremely rare cause of obesity, "but at the same time, studying these subjects will help us to understand how leptin regulates body weight in humans," explains Dr. Louis Aronne, clinical professor of medicine at Weill Medical College of Cornell University and director of the New York Presbyterian Hospital Comprehensive Weight Control Program.

Licinio hopes that, future research will discover ways to increase obese people's sensitivity to leptin, or possibly discover new drugs that are similar to, but more potent than, the leptin available now.