Fat is an Organ!
Research shows fat is an organ
Guides new research, explains ruined diets
Brad Evenson
National Post
Monday, September 08, 2003
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In the anatomy textbooks, the major organs are easy to find. The liver is always
brown, the spleen is green, the heart is red and the small intestine is squeezed
like a row of sausages into the abdomen. But one of the principal organs,
present in close to 50% of North American men and women, is missing. Fat.
Fat cells are the colour of jaundice, greasy and thousands of times bigger than
other cells. The average adult has close to 35 billion fat cells, or adipocytes,
a number that balloons as high as 275 billion in the very obese.
It was the accepted wisdom that these cells lived quiet lives as the body’s
cushions, insulation and fuel tanks. But in recent years, scientists have been
stunned to learn fat is very busy indeed.
When fat cells accumulate into a large enough mass, they begin pumping out a
toxic array of chemical signals.
“It’s a nasty soup that comes from our [fat cells],” says Daniel Drucker, a
University of Toronto researcher.
Many scientists now consider fat an endocrine organ, like the pancreas. And
nobody will ever want a transplant.
This explains why having a big pot belly often foreshadows such woes as
diabetes, cancer and hardened arteries.
“Think of it as a tumour,” says another researcher. “One that’s caused by soft
drinks and french fries.”
If more people realized their “love handles” are in fact toxic, they might work
harder to get rid of them, experts believe.
Our new understanding of the secret life of fat has transformed the field of
obesity research. Scientists now understand that blocking the molecular signals
that fat transmits to the brain and body could lead to a thin pill. And that
could be worth billions of dollars.
“It’s almost like a gold rush now,” says David Lau, a University of Calgary
endocrinologist and president of Obesity Canada, a non-profit research
organization. “Everyone is looking for the magic bullet.”
The rush started in late 1994, when researchers at Rockefeller University
discovered that fat cells secrete a hormone called leptin. Derived from the
Greek word, “to thin,” leptin acts on the hypothalamus in the brain, where the
hunger and satiety centres are located. It was the first time research had shown
fat can control appetite. Fat deposits, it dawned on scientists, are really
organs.
“[Leptin] was the transformational discovery,” says Dr. Drucker. “The world
realized fat is more of an active player than we previously appreciated.”
Since the discovery of leptin, researchers have found dozens of molecules made
by fat.
A little fat is essential to human survival. In normal amounts, fat cells make
adiponectin, a beneficial hormone that makes the body more sensitive to insulin.
But too much of a good thing can kill.
A never-ending avalanche of new studies show that when large numbers of fat
cells accumulate, especially in the belly — creating the dreaded “apple-shaped”
body — they begin secreting chemicals known as adipokines, many of which
trigger disease.
For example, an adipokine known as resistin — resistance to insulin — is
believed to cause blood sugar levels in the body to rise, leading to type 2
diabetes. More than 150 million people around the world suffer from this
disease, a number predicted to rise to 280 million by 2025.
“This is just a huge epidemic in the world,” says Bernie Zinman, director of the
Leadership Sinai Centre for Diabetes at Mount Sinai Hospital in Toronto.
“There are 1.5 million Canadians who have been diagnosed with diabetes, and
about 750,000 who have it but don’t know it yet.”
Accumulations of fat also churn out tumour necrosis factor-alpha (NTF-a), which
causes rheumatoid arthritis, and C-reactive protein, which is linked to
atherosclerosis and heart disease. This explains why obese people are often
stricken with multiple health problems, which often vanish when they lose
weight.
However, a person who was once fat is different from someone who was always
thin.
“If I gain 20 kilograms and then I lose 20 kilograms, it’s not certain I will
have exactly the same biology as if I had not gained,” says Angelo Tremblay, a
professor of preventive medicine at Laval University in Quebec City.
This is because humans are born with billions of tiny “baby fat cells,” called
preadipocytes. If we consume too many calories, filling our adult fat cells to
bursting, they send out a molecular signal to the preadipocytes to mature.
Before they can grow up to a life of storing body fat, however, these immature
fat cells must divide at least twice. So not only do billions of new adult fat
cells add to a burgeoning waistline, billions more baby fat cells are born.
Diet and exercise reduce the amount of fatty oils stored in each of these fat
cells. But they don’t reduce the overall population of fat cells, with their
cellular machinery, which may continue to pump out nasty adipokines, screwing up
the body’s normal hunger and satiety signals. This is why diets often tend to
fail. Once fat, people will always struggle against their own bodies to be thin,
which is why most obesity experts place their greatest hopes on prevention, not
cure.
“Childhood obesity is where we’re really falling down,” says Dr. Zinman.
Children who are obese, carrying a fat organ in their bodies for decades, are
more likely to face long-term medical woes.
Some experts say it’s useful to compare fat to cancer, particularly since the
growth and proliferation of new fat cells can sharply increase the risk of
breast, prostate, colon and other cancers. Studies now link the adipokines that
switch on baby fat cells to the growth of these cancers, which means the same
molecular forces that expand girth also expand tumours.
Reducing weight can prevent the formation of these new fat cells and the cancer
risk that rises with them.
“If you can reduce body weight, you can reduce cancers,” Dr. Lau says.
“If they’re told they’re 40 pounds overweight, people think, ‘Don’t worry, I can
knock that off sometime,’ ” Dr. Drucker says. “But if you tell them they have
cancer and they’re going to lose 15 years of their life, they don’t take it so
lightly.”
The cancer analogy is now being applied to research, where some scientists are
destroying fat cells using a method of killing cancer. Last year, U.S.
researchers used a promising type of anti-cancer drug, which deprives tumours of
a blood supply, to combat weight gain in rodents. The endeavour was based on the
idea that fat tissue, like tumours, requires an extra supply of blood to grow.
Fat tissue is filled with tiny blood vessels, which proliferate as the body
thickens.
Maria Rupnick, a researcher at Brigham and Women’s Hospital in Boston, fed obese
rats with experimental cancer drugs known as angiogenesis inhibitors to prevent
excess weight gain. The drugs did more than prevent gain. The overweight mice
lost significant amounts of fat — in some cases 50% of their bodyweight.
“We were surprised by how much weight they lost,” says Dr. Rupnick, who reported
the discovery in the journal Proceedings of the National Academy of Sciences.
Dr. Rupnick says fat tissue, like tumours, probably has fewer stable blood
vessels than the rest of the body. The drugs probably destroyed capillaries in
the fat tissue, leading to the death of fat cells. Moreover, once the “fat
organ” had disappeared, the mice developed a normal appetite.
Dr. Rupnick says further study is needed to understand the drugs’ effects.
Until then, or until a magic bullet is found, new anatomy textbooks should add a
bright yellow organ to diagrams of the abdominal cavity.
Part two of a six-part series.; Tomorrow: Sixteen-year-old Jessica was so scared
of being taunted about her weight that she became a recluse, rarely leaving her
home. Now, she has joined the growing ranks of teens and children who have their
stomachs stapled in the hope surgery will succeed where diets have failed.;
bevenson@…
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