Decoding the Surprisingly Active Life Of Fat Cells

For decades, scientists thought fat cells were passive blobs that did nothing more than store energy, bloat flabby hips and bellies, and perhaps wear down the body by forcing it to cart around a lot of extra weight.

But as the nation's obesity crisis has intensified scientific interest in fat, researchers have fundamentally altered that view: Fat cells, they now realize, are extraordinarily dynamic, complex and influential entities that affect a staggering array of crucial bodily functions.

The new insights into fat's commanding, self-sustaining powers, scientists say, have profound implications for understanding how flab forms, why it hangs on so stubbornly, how it causes disease, and therefore possibly how to help people shed pounds and avoid the devastating health problems wrought by fat cells.

"They were always thought to be poor, dumb sacks of lard," said Roger Unger, an obesity researcher at the University of Texas Southwestern Medical Center. "It turns out that they end up being very talented, very versatile, very important players."

Instead of sitting idly by, waiting for a famine or a foot race, fat cells continuously dispatch dozens of potent chemical signals to myriad tissues throughout the body, including the brain, liver, muscles, reproductive organs and immune system, orchestrating a host of activities.

"Knowing its whole communication network is going to help us answer many important questions, and possibly lead us in a direction to cure obesity and therefore the diseases caused by obesity," said Barbara Corkey, a Boston University scientist who serves as president of the North American Association for the Study of Obesity.

Like guardians of the nation's strategic oil reserve, fat coordinates how, when and where the body's energy supply is stored and how and when it is mobilized. Fat also emits signals that can unleash, or damp down, the immune system. Fat influences when blood clots and when blood vessels constrict. Fat even tells the body when it can reproduce, and when it must await more favorable conditions. And perhaps most insidiously, fat cells most likely beget new fat cells, perpetuating their existence and magnifying their effects.

"In the old days, people used to think fat tissue was a passive organ," said Rexford S. Ahima, an endocrinologist at the University of Pennsylvania. "Now it's obvious that it makes and secretes more hormones and proteins than probably any other. It's at the center of a very complex system. It coordinates how much we eat, how much energy we burn, how the immune system works, how we reproduce. The list goes on."

And scientists suspect they have just begun to unravel the intricate web of fat's reach, with perhaps dozens of other functions and signals awaiting discovery, including some that probably affect mood and behavior beyond just hunger and eating.

"Many people think your brain controls your fat," said Gokhan S. Hotamisligil, a professor of genetics and metabolism at the Harvard School of Public Health. "We promote the idea that your fat controls your brain."

The new understanding has led to the discovery of new chemical messengers that fat cells deploy, and drug companies are scrambling to find ways to manipulate those hormones to help people lose weight and avoid the health problems associated with obesity.

"Once you know the players you can try to cage them in," said Xavier Pi-Sunyer, chief of endocrinology at St. Luke's-Roosevelt Hospital in New York.

The new insights also may help alter societal views of obesity, further undermining the notion that obesity is a sign of moral defect and bolstering the case that it is a discreet and stubbornly self-perpetuating biological state.

"The rules of the game have changed. The way you look at an individual who is obese has to be radically changed as a result of this," said Rudolph L. Leibel, a molecular geneticist at Columbia University. "Before the naysayers could say this is all free will and has nothing to do with biology. I don't think anything could be farther from the truth."