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http://content.nejm.org/this_week/346/21/index.shtml



(AP) --A hormone thought to boost appetite rises in the bloodstream
after dieters lose lots of weight, possibly explaining why it's so hard to
keep weight off long term -- and offering a new target for a diet drug,
researchers say.

Their small study of severely obese people found much higher levels of
a recently discovered hormone made by stomach cells, ghrelin, in the
blood after the patients had lost significant weight.

However, very little ghrelin was in the blood of several people who lost
weight after gastric bypass surgery, an operation that sews shut 95
percent of the stomach and reroutes the flow of food.

"Not only did (ghrelin levels) not go up, but in people who lost an
enormous amount of weight, it went way down," said Dr. David E.
Cummings, an endocrinologist who led the researchers at the University
of Washington and the Veterans Affairs Puget Sound Health Care
System.

Cummings and Dr. Mitchell S. Roslin, chief of obesity surgery at Lenox
Hill Hospital in New York, say the abnormally low ghrelin levels after
gastric bypass could help explain why it is more successful than dieting
or operations that simply reduce stomach size.

Ghrelin is thought to be nature's way of making people fatten up when
food is plentiful to increase survival during cycles of famine, a
protective mechanism now harmful when plenty of high-calorie food is
available.

The researchers and other experts say the findings are circumstantial
evidence of ghrelin's effects, and more research is needed.

"This is a first step, and it may be an important hormone, but we don't
know that yet," said Dr. Xavier Pi-Sunyer, former chairman of the
National Heart, Lung and Blood Institute's obesity task force and director
of the Obesity Research Center at St. Luke's/Roosevelt Hospital Center in
New York. "It's not like this is a breakthrough."

The body has multiple backup systems for regulating body weight,
probably including other hormones not yet discovered, said Dr. Stephen
H. Schneider, director of diabetes services at UMDNJ-Robert Wood
Johnson Medical School in New Brunswick, New Jersey.

"This is probably one of a number of substances which control appetite,"
and it's unclear how they interact, he said.

The study, reported in Thursday's edition of the New England Journal of
Medicine, involved patients who had sharply reduced their weight and
kept stable for three months. Five patients who had gastric bypass
surgery dropped from an average of 435 pounds to 280 pounds, while
13 people on a supervised low-fat, liquid diet dropped from an average
weight of 220 pounds to 182 pounds.

In the diet group, ghrelin levels were consistently about 50 percent
higher after weight loss. Levels spiked before meals and plunged after,
both before and after weight loss.

The bypass group had barely detectable ghrelin levels and on average
had 72 percent less ghrelin than five dieters who ended up at about the
same body mass index, a ratio of weight to height. The bypass patients
also had 77 percent less ghrelin on average than a comparison group of
10 normal-weight people.

Some 75,000 to 100,000 severely obese Americans are expected to
undergo some type of bariatric, or stomach-reducing, surgery this year.
Gastric bypass is meant only for people at least 100 pounds overweight.

Ghrelin, discovered about two years ago, has a role in promoting
growth, from making children taller to building bone density.

Injecting the hormone in rodents makes them eat right away, but ghrelin
has not been proven to stimulate appetite in people. Still, several major
pharmaceutical companies are trying to develop drugs to block the
hormone, Cummings said.

"A true cure for obesity would be the biggest moneymaker that any drug
company's ever seen," he said.