A Family Affair from ABC News
Hormone Leads to Dramatic Weight Loss for Three Cousins
Aug. 7
— 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.