Obesity kills — in many ways

Third in an occasional series.

Research into the biology of fat is turning up some surprising new insights about how obesity kills. The weight of the evidence: It's the toxic mischief of the flesh itself.

Experts have realized for decades that large people die young, and the explanation long 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 and sleep apnea, among other things, it is a minor hazard compared to the complex and insidious damage wrought by the oily, yellowish globs of fat that cover human bodies like never before.

A series of recent discoveries suggests 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 to capacity with fat, they assault many organs in ways that are bad for health.

The exact details are still being worked out, but scientists say there is no doubt this flux of biological crosstalk hastens death from heart disease, strokes, diabetes and cancer, diseases that are 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."

The first real inkling that fat is more than just 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 producing a chemical that regulates appetite.

Roughly 25 different signaling compounds — with names like resistin and adiponectin — are now known to be made by fat cells, Leibel estimates, and many 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. That is enough fuel to keep someone alive without eating for three months.