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The Hunger=20 Hormone
Aug. 13,=20 2003


The United=20 States is the fattest nation on earth. Two-thirds of Americans are = overweight.=20 Nearly 59 million are considered obese, putting them at risk for = diabetes, heart=20 disease and high blood pressure.

We=92re all casualties of a = battle=20 between our genes and our fast food culture. And now, it turns out we = may be=20 casualties of a hormone called ghrelin.

Ghrelin is the hunger = hormone.=20 It=92s made in the stomach, and it tells the brain when it=92s time to = eat. Ghrelin=20 doesn=92t cause obesity, but scientists think taming it might help us = get our=20 scales back in balance.

They=92re also investigating an opposite = hormone =96=20 PYY =96 that makes you feel full.

So, as 60 Minutes = II asked=20 this spring, what if we could take a drug that would shut off our = ghrelin or=20 boost our PYY?

In labs around the country, the race is on to = find out.=20 Correspondent Vicki Mabrey reports.
The search for a billion-dollar solution to fat begins with mice. =

In a=20 lab at the St. Louis Veterans Affairs Hospital, and in others like it,=20 scientists are studying rodents to learn about the human appetite. = They=92re=20 trying to find out why the hormone ghrelin makes a mouse so ravenous. =

We=20 observed one illustration of ghrelin=92s power. A mouse was injected = with the=20 hormone. Just 15 minutes later, he was absolutely wild for food, even = though=20 he=92d already eaten enough to be full.

Scientists are finding = that=20 ghrelin has the same power over people.
That discovery was made in = part=20 through the experience of a man named Jim Rudolph, who used to weigh 460 = pounds.=20

Taking a stroll along Seattle=92s waterfront, Rudolph says, = =93I=92m so happy=20 to be able to walk like this today.=94 Not long ago, he couldn=92t walk, = drive or=20 fit into one airplane seat. He also needed an electric cart to get = around.=20

Then, a pair of size 65 pants was a tight fit. He saved them to = show=20 60 Minutes II that he can now fit into one of the pant = legs.=20

Four years ago, Jim Rudolph underwent gastric bypass surgery. = Such=20 stomach reduction procedures are on the rise. Last year alone, 60,000 = obese=20 Americans went under the knife.

He lost 195 pounds after his = procedure.=20 But that=92s not surprising, since gastric bypass reduces the stomach by = 95=20 percent.

What is surprising, scientists say, is what Rudolph=92s = surgery=20 revealed about appetite, and about the only hormone known to trigger it. = The=20 surgery seems to have killed the ability of Jim Rudolph=92s body to = produce=20 ghrelin, or at least it put that function to sleep.

=93I don=92t = seem to get=20 really hungry,=94 he says. =93It=92s not necessarily hunger like the old = hunger,=20 going, you know, =91Feed me.'=94
Dr. David Cummings, an endocrinologist at Seattle=92s Veterans = Administration=20 Medical Center and the University of Washington, studied Rudolph and = four other=20 gastric bypass patients.

His team=92s findings have captured the = attention=20 of scientists around the world, and have spurred the race to find a less = drastic=20 way than gastric bypass surgery to block ghrelin.

Recently, = Cummings=20 showed off a test tube. =93At the bottom of this tube is a little tiny = fleck of=20 stuff, which is pure dried ghrelin,=94 he says.

What would = happen to=20 someone who ate that tiny bit of ghrelin?

=93You=92d want to = eat,=94 says=20 Cummings. =93You=92d want to eat right away.=94

Japanese = scientists discovered=20 ghrelin in 1999. A year later, American researchers found that it drives = appetite.

=94Ghrelin is the first and only yet-described=20 appetite-stimulating hormone,=94 says Cummings, explaining that ghrelin = is mainly=20 created in the stomach, where it circulates in the blood, eventually = sending a=20 message to the brain to stimulate appetite.

Cummings and his = team=20 studied ghrelin levels in obese dieters and in people of normal weight. = They=20 found that people who lost weight through dieting actually had elevated = levels=20 of ghrelin - not just occasionally, but day and night, whenever it was = measured.=20

"Implication is that this is one of the ways in which the body = fights=20 against weight loss," says Cummings, which might help explain why = millions of=20 yo-yo dieters can=92t keep the weight off.
One of those dieters is Hillary Bargar Strackbein, a Connecticut = prosecutor.=20

=93I=92m a lifetime member of Weight Watchers,=94 she says, = =93and I=92m a=20 successful Weight Watcher who lost about 90 pounds on Weight Watchers = [and]=20 gained it all back.=94

But that=92s not all. She also went on = the Jenny=20 Craig diet: =93I lost about 100 pounds, gained it all back ... then = there's the=20 the Atkins diet. I was on a grapefruit diet, soup diet." =

Basically,=20 she=92s been dieting pretty much all of her life.

Three years = ago, Bargar=20 Strackbein tipped the scales at 255 pounds. At that weight, she was = ashamed to=20 appear in court.

Most recently, she put herself on a virtual = starvation=20 diet, eating only one 700-calorie meal a day. By living mostly on soy = burgers=20 and omelettes, and by exercising daily, Bargar Strackbein lost more than = 100=20 pounds.

Even so, her weight kept creeping back up, so she = contacted=20 Cummings about his research.

What he told her was actually a = relief: =93He=20 said, =91The reason you feel your body=92s trying to gain weight back is = because it=20 is. Your body is against you.=92 It was the first time I ever saw a = doctor or=20 anyone say, =91You=92re right. I believe you. You=92re not bingeing. = You=92re doing what=20 you=92re doing and it=92s still not working right.'"

So, is = Bargar=20 Strackbein fighting a losing battle? Cummings says she may be: =93I have = to say=20 that just playing the numbers, I would predict that she will not be able = to=20 maintain that weight loss, but I encourage her to try.=94

He = says that=92s=20 because each of our bodies has a genetic set point. In effect, your = genes=20 establish your weight range, and puts you in a body weight ballpark.=20

"Within that ballpark, you can slide up or down about five or 10 = percent, with dieting and exercise and the use of a few available = medications we=20 now have,=94 says Cummings. "And for most people, not much more than = that is=20 attainable or sustainable.=94=20
So, are we battling biology or bad habits? British obesity researcher = Stephen=20 Bloom says both.

=93We are machines designed to live through = famine,=94 says=20 Bloom. =93In the days when we evolved, there would be a good harvest for = six years=20 and a bad harvest in the seventh year. And the only people who lived = through the=20 seventh year were the ones that were overweight. So, if you were able to = watch=20 your weight very nicely, you aren=92t here anymore. We are survivors of = the obese.=20 All we need is a plentiful supply of food and we gain weight. That=92s = the way we=20 are made.=94

At London=92s Imperial College, Bloom and his team = are also=20 studying ghrelin. But recently, they began experimenting with another = hormone=20 called PYY-336. You could almost call it the anti-ghrelin because this = hormone=20 makes you feel full.

In Bloom=92s study, hungry human volunteers = were=20 given PYY, and then offered an all-you-can-eat lunch. Researchers = measured the=20 leftovers, and found there was a lot left over. In fact, the test = subjects ate=20 one-third less for the full 24 hours after receiving PYY.

The = theory is,=20 ghrelin goes to the brain and hunger sets in. "The ghrelin's disappeared = after a=20 meal, but the hormone to stop you eating, PYY, has risen in the = bloodstream,"=20 says Bloom. "And as long as it's high, it stops you feeling hungry." =

The=20 evidence on ghrelin and PYY has so convinced Bloom that he=92s = practically given=20 up on the common prescription of =93eat less, exercise more.=94 He now = says obesity=20 has to be treated like any other illness, with medication. =

=93The advice=20 we give people does not seem to work,=94 he says, =93so the answer is, = as we have=20 with blood pressure, take a tablet. As we have with cholesterol, take a = tablet.=20 So, I fear, with overweight, we have to damp down appetite. We can=92t = actually=20 control ourselves. We have to accept that as a fact."

A diet = expert=20 advocating a magic pill for losing weight? =93I hate it," says Bloom. = "But I can=92t=20 think of anything better."=20
A magic pill that is safer and more effective than what=92s on the = market now=20 would be worth billions of dollars to pharmaceutical companies. =

60=20 Minutes II got a rare look into a laboratory at Eli Lilly, where = Dr.=20 Mark Heiman, whose team first establishe that ghrelin made rodents = hungry, is=20 leading the search for a ghrelin blocker.

He showed us a sample = of just=20 one of the substances being tested that may be a potential weapon for = keeping=20 weight off.

The ingredients of that powder are top secret, of = course.=20 And with the stakes so high and competition so fierce, drug = manufacturers almost=20 never allow cameras in.

Under a microscope, Heiman showed us = ghrelin=20 cells in the lining of the stomach. The fact that ghrelin is = manufactured in the=20 stomach, not in a riskier area like the brain, makes researchers hopeful = that=20 they can come up with a blocker.

But don=92t look for that magic = pill=20 soon. =93This is a long, long process,=94 says Heiman. =93It would = probably be about=20 ten years before it=92ll be in the pharmacist=92s shelf."
Doctors Heiman and Cummings hope to test the ghrelin blocker on people = like Matt=20 Heineman, 29, who suffers from a rare genetic disorder called = Prader-Willi=20 syndrome.

People who suffer from Prader-Willi suffer from slowed = development, severe obesity and insatiable appetite. Matt=92s mother, = Janalee=20 Heinemann, says it=92s a struggle to keep them alive. =

=93They=92ll just eat=20 till they die. I mean, until they=92re so obese they can=92t breathe, = that they have=20 right-sided heart failure, that they have diabetes, etc.,=94 she says. =

In=20 other words, they literally eat themselves to death.

It=92s a = condition,=20 she says, that forces parents to act like jailers. To fight his = uncontrollable=20 urge to eat, Matt=92s mother locked the refrigerator and cupboards, and = monitored=20 Matt wherever he went.

Even now, as an adult, Matt has to live a = =93safe=20 house.=94 60 Minutes II visited one outside St. Louis, = where=20 everything in the kitchen is kept locked and counselors search residents = for=20 unauthorized snacks and weigh them twice a day to make sure they=92re = not sneaking=20 food.

Cummings has found that ghrelin levels in people with = Prader-Willi=20 are off the charts: =93We examined ghrelin levels in these people and = found them=20 to be among the highest that have yet been recorded in any humans.=93 =

As=20 one sufferer puts it, it feels like piranhas are in your stomach all the = time.=20

The thinking is that if a ghrelin blocker can cut the appetite = of people=20 with Prader-Willi syndrome, it could help others with less severe = obesity=20 problems.

But don=92t get your hopes up yet. This isn=92t the = first time the=20 Holy Grail of weight loss has appeared to be close at hand. Some earlier = remedies have led to serious and sometimes deadly side effects. =

The St.=20 Louis researchers injecting mice with ghrelin are looking at other = aspects of=20 the hormone. Early evidence indicates ghrelin also may affect memory as = well as=20 growth and appetite. A ghrelin blocker could have an effect on all of = those=20 things.

So, is there ever going to be a magic pill that is going = to make=20 us as thin as we want to be?

=93I don=92t think that there=92s = ever going to=20 be a single medicine that would prove to be the magic bullet for all = people,"=20 says Cummings. "But I think there=92s reason for hope that we may have, = one day,=20 half a dozen magic bullets that can be used in combinations to help = people with=20 their body weight in much more powerful ways than we now can do.=94=20




=A9 MMIII,=20 CBS Broadcasting Inc. All Rights Reserved.
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