| Feeling famished? Or so full
you couldn't eat another bite? It may be all in your head.
Research has shown when it comes to appetite, certain hormones, enzymes
and genes all play a role in signaling the brain when it's time to eat.
Understanding how these mechanisms interact is a key pursuit in the United
States, where two-thirds of the population is overweight and nearly 59
million are obese.
Keeping the pounds off is also an expensive problem. Researchers at the
Center for Disease Control and Prevention in Atlanta recently estimated
weight-related health problems cause $93 billion in U.S. treatment costs
every year.
"We've been telling people for more than 150 years that in order to
prevent obesity, they need to eat less and take more exercise," said
Stephen Bloom, a British obesity researcher at London's Imperial College.
"And yet the population has gotten fatter and fatter and thousands of
people die unnecessarily every week because they overeat. So obviously it
doesn't work."
What could work, argue Bloom and others, is fooling the brain into
thinking it's full.
The Hungry Hormone
This has certainly been tried before. A popular diet-drug cocktail of
fenfluramine and phentermine, known as fen-phen, entered the market and
then exited when it was determined it could have dangerous side effects on
the heart.
Ephedra, an herbal diet supplement, will soon carry warning labels
following the February heatstroke death of Baltimore Orioles pitcher Steve
Bechler, who had been taking the supplement. Other pills remain available
and carry no warnings, but appear to be less effective as weight-loss
aids.
Recently, however, scientists have directed their attention to a small
group of hormones and enzymes that, they believe, could play a role in
developing a diet wonder drug.
Among the hottest targets are the hormones known as ghrelin and PYY.
Japanese scientists discovered ghrelin in 1999 and American researchers
proved its role in appetite a year later.
According to work by David Cummings, an endocrinologist at Seattle's
Veterans Administration Medical Center at the University of Washington,
ghrelin is produced in the stomach and, when delivered to the brain, tells
the body to eat — immediately.
What's more, Cummings research showed that obese people who are dieting
and losing weight have increased levels of the hungry hormone in their
blood. The more pounds they lose, the more their bodies demand they eat
more to make up the difference.
By finding a way to artificially reduce the level of ghrelin in the blood,
scientists hope to turn off the body's demand to eat.
The ‘Stop Eating’ Signal
Ghrelin appears to have a counterpart — another hormone that sends the
opposite signal — telling the brain to hold off the forkfuls.
PYY, which stands for peripheral hormone peptide YY (PYY 3-36), is
secreted in the gut and released on a bundle of brain neurons in the
hypothalamus that control appetite.
Tests on mice suggest that infusing even small amounts of the hormone into
the bloodstream leads to dramatic weight loss. And Bloom and colleagues
have shown that tinkering with levels of PYY in people works to suppress
appetite.
When his team at Imperial College infused a test group with the hormone
they ate a third less food from a free, fancy buffet than people who had
received a placebo infusion of saline. Both groups had refrained from
eating for a day before the test to ensure they had hearty appetites.
"We need to do further human studies to prove there are no side effects
when you take it every day and we need to show it would work in the very
overweight," Bloom said. "But right now it's looking like a strong
solution."
Failed Promise
It remains to be seen whether ghrelin or PYY are sensible targets or just
more dead ends in the search for the perfect diet drug. Other discoveries
have looked equally promising in the past.
In 1994, for example, a Rockefeller University scientist identified a
mouse gene that makes a protein called leptin. Mice bred without the
leptin-producing gene grew to be grossly obese while those with higher
levels of leptin stayed slim.
The fervent hope was by packaging leptin in a pill, dieters might finally
get the help they need to resist overeating. But follow-up studies showed
that, thanks to genetics or lifestyle patterns, many overweight people and
nearly all obese people tested already have unusually high levels of
leptin in their blood and seem to lose their sensitivity to it. So leptin
boosts proved to be no help.
But slumps like these can lead to new discoveries.
Ludiano Rossetti, for example, was investigating why some people lose
sensitivity to leptin when he found that hormones and proteins aren't the
only things sending "stop eating" signals to the brain. It turns out
nutrients, themselves, send signals as well.
Rossetti, a medical researcher at Albert Einstein College of Medicine in
New York City, found that when fats are digested, the enzymes used to
break down the fat tell the brain that the body's getting full. Rossetti
is eager to find out if increasing levels of this enzyme in the brain
could be a more direct method of helping people cut back on eating.
"I think what we've been learning in the past decade is the body is full
of responses that are designed regulate how much we eat," he said. "It's a
tightly controlled system."
Exercise, Exercise, Exercise
Because we have such "precisely controlled systems," many health experts
have concluded it's best to simply try and work with what we've got. That
of course, involves following the well-known refrain: eat right and
exercise.
Lisa Sutherland, a nutritionist at the University of North Carolina at
Chapel Hill, believes that exercise may be the most important part of that
prescription.
"When I was growing up I had physical education in schools five days a
week and only three channels on TV," she said. "That has changed and I
think that may be a big part of the problem."
Sutherland analyzed federal data on the diet and weight and physical
activity of teens from 1980 to 2000 and found that kids in the most recent
year were eating only 1 percent more calories while their level of
physical activity dropped by 13 percent.
William Banks, a professor of geriatrics at Saint Louis University School
of Medicine and the Veterans Affairs Medical Center, points out that some
may have to work harder than others at staying slim, thanks to genetics.
(See sidebar below.)
Still, unlike Bloom, Banks is hopeful that eventually the eat less and
exercise mantra will stick.
He points out that in the 19th century, obesity was more common among
those with wealth, since wealthier people could afford more comfortable
lifestyles. Today the reverse is true — those in higher socioeconomic
groups are less overweight than those who have less.
"This shift suggests people can educate themselves and introduce important
lifestyle changes," he said. "It's hard because we're so entrenched in a
calorie-ridden society. But it's possible."
Lazy Baboons Prove Genetics Count
A study of wild baboons shows that staying active is key to staying trim,
but some may be able to skip exercise and still avoid weight gain thanks
to their genes.
William Banks, a professor of geriatrics at Saint Louis University School
of Medicine, recently analyzed the eating and exercise patterns of two
sets of baboons in East Africa. One group lived normal baboon lifestyles
and traveled widely throughout the forest every day to forage for food.
The others discovered they could feed with little effort from garbage bins
outside a nearby a tourist area.
"What they were eating included about the same amount of calories," Banks
said. "The difference is the garbage-eating baboons weren't expending much
effort."
It wasn't surprising to Banks that there were plump baboons among the
garbage-eating group. Tests showed these baboons also had unhealthy levels
of glucose, insulin and cholesterol in their blood. Among the foragers,
there were no overweight baboons.
What was surprising, however, is that some of the garbage-munching baboons
did not get fat. The conclusion? When it comes to diet and weight gain,
life isn't fair.
"It's like in people," Banks said. "Many of us live in the same caloric
environment, but some people weigh more than others. It's always a
combination of genetics and environment." |
