Fat isn't just a load to bear — it's often the body's biggest organ

By Daniel Q. Haney
The Associated Press

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Experts have realized for decades that large people die young, and the explanation seemed obvious. Carrying around all those extra pounds must put a deadly strain on the heart and other organs.

Obvious but wrong, it turns out. While the physical burden contributes to arthritis, sleep apnea and other things, it is a minor hazard compared with the complex and insidious damage wrought by the oily, yellowish globs of fat that cover our bodies like never before.

Recent discoveries suggest that all fat-storage cells churn out a stew of hormones and other chemical messengers that fine-tune the body's energy balance. But when spewed in vast amounts by cells swollen with fat, they assault organs in ways bad for health.

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Details are still being worked out, but scientists say there's no doubt this flux of biological crosstalk hastens death from heart disease, strokes, diabetes and cancer — diseases especially common among the obese.

"When we look at fat tissue now, we see it's not just a passive depot of fat," says Dr. Rudolph Leibel of Columbia University. "It's an active manufacturer of signals to other parts of the body."

Fat cells send dangerous signals

The first inkling that fat is more than inert blubber was the discovery 10 years ago of the substance leptin. Scientists were amazed to find that this static-looking flesh helps maintain itself by making a chemical that regulates appetite.

Roughly 25 signaling compounds are now known to be made by fat cells, Leibel estimates, and more undoubtedly will be found.

"There is an explosion of information about just what it is and what it does," Dr. Allen Spiegel, director of the National Institute of Diabetes and Digestive and Kidney Diseases, says of fat. "It is a tremendously dynamic organ."

Fat tissue is now recognized to be the body's biggest endocrine organ, and its sheer volume is impressive even in normal-size people. A trim woman is typically 30 percent fat, a man 15 percent — enough fuel to keep someone alive without eating for three months.

The fat cell's main job is to store excess calories. When people grow obese, their fat cells swell with fat and can plump to three times normal size. As the very overweight get fatter still, they may layer on many more fat cells.

The problem is the volume of chemicals these oversize cells churn out, says Dr. George Bray of Louisiana State University. "The big cell secretes more of everything that it secreted when it was small. When you get more of these things, they are not good for you."

Many scientists are trying to learn exactly what these excess secretions do that is so harmful. The answers will help explain — and perhaps offer solutions to — the real tragedy of obesity, its disastrous effect on health.

Heart disease is still biggest threat

Obesity is a huge and growing killer, in the U.S. Moderately obese people live two to five years less than normal-size folks. For the severely obese, it can be 10 years.

The biggest threat is heart disease. Someone with a body-mass index over 30 has triple the usual risk. Scientists can visualize many ways that fat cells' chemical flood contributes to heart attacks, heart failure and cardiac arrest.

It has long been known that weight increases blood pressure. Now it is clear that fat can trigger high blood pressure by making blood vessels narrow in several chemical ways. It produces a substance called angiotensinogen, a powerful constrictor. And it stimulates the sympathetic nerves to squeeze the circulatory system. That may just be the beginning.

"It's a very complicated system, and the more we learn about it, the more complicated it becomes," says Dr. Xavier Pi-Sunyer, head of obesity research at New York's St. Luke's Roosevelt Hospital Center.

One of the clearest hazards of overfilled fat cells is their influence on insulin, the hormone that instructs the muscle to burn energy and the fat cells to store it. Oversize fat cells blunt the insulin message, in part by leaking fat into the bloodstream. So the pancreas must compensate by making more insulin.

Scientists now understand that increasing insulin levels — part of a condition called insulin resistance — are particularly harmful. They can directly damage the artery walls and lead to clogging.

The leaking fat may also infiltrate the heart muscle, contributing to congestive heart failure. Misplaced fat deposits also ruin the liver and have become the second-leading reason for transplants.

Fat cells churn out a variety of inflammatory proteins, too. These may be especially destructive to the gunky buildups in the arteries, causing them to burst and triggering heart attacks and strokes.

These proteins and other fat-driven chemicals, such as growth hormones, may also contribute to one of the less appreciated consequences of obesity — cancer.

"There is now conclusive evidence that obesity causes some cancers and strong evidence that it contributes to a wide variety of others," says Dr. Michael Thun, epidemiology chief at the American Cancer Society.

The cancer society estimates that staying trim could eliminate 90,000 U.S. cancer deaths a year. Among varieties linked to weight are cancer of the breast, uterus, colon, kidney, esophagus, pancreas and gallbladder.

The best evidence of how obesity causes malignancy is in breast cancer in older women. When the ovaries shut down after menopause, fat tissue becomes the No. 1 producer of estrogen, which can fuel the growth of breast tumors.

The heavier women are when diagnosed with breast cancer, the more likely they are to die from the disease, says Dr. Michelle Holmes of Boston's Brigham and Women's Hospital.

Still, big-ticket killers like heart disease and cancer only start the long list of obesity's health ills. Among other things, the obese are more prone to depression, gallstones, even dying when in car accidents.

Copyright © 2004 The Seattle Times Company

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