fat and angiogenesis

[Cary]

Research shows fat is an organ

Guides new research, explains ruined diets

Brad Evenson

National Post

Monday, September 08, 2003

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.

[Ry]

Holy hell Cary if this doesn't get me some new members in the diet club nothing will! This is gross!

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.

I really didn't need to know this!

[Cary]

I wonder what angiogenic drug they used. I think if we could locate this information okdebi might have a chance at winning the diet contest. LOL

[Ry]

Oh no, don't encourage her! Who knows what she'll type in her search engine and where she'll go this time. But hey, I'm not messin' with her she knows where I live and she's been known to stalk people.

[Cary]

What I don't get is, why does she even need to lose weight. she was gorgeous in her bikini avatar. I guess some people are just never happy with their bodies.

Cary

[Ry]

LOL!

Hey tell me about it, that picture even got my husband on the board!

[Debi]

Okay, Cary, what the hell is that?? You sure ruined that pint of Ben & Jerry's I had jammed in the corner of the freezer for a rainy day. I wonder if other people can remember the exact moment they turned anorexic???

Oh, and Ry, gatherer of phone numbers and addresses.... I'M the stalker????