Will We Keep Getting Fatter?

By MICHAEL D. LEMONICK

If the past 2 million or 3 million years of human history are any guide, obesity is our unfortunate but inevitable fate. That's not to say there's any special secret to weight control. All it takes, as we've heard over and over, is a sensible diet and plenty of exercise.

But knowing and doing are two very different things, as hundreds of thousands of lapsed weight watchers have learned to their despair. The trouble, according to one theory, is that our best intentions about weight control go up against several million years of human evolution. Our hunter-gatherer ancestors literally didn't know where their next meal was coming from. So evolution favored those who craved energy-rich, fatty foods--and whose metabolism stored excess calories against times of famine. Love handles, potbellies, thick thighs are all part of Mother Nature's grand design.

From about 2.5 million B.C. to, say, 100 years ago, the system worked fine. Only a tiny percentage of humans had unlimited access to food and no need to lift a finger on their own behalf. What happened to them? Picture Henry VIII. But over the past century or so, most Americans have been living like kings. Thanks to increasingly high-tech farming methods, the fatty foods we crave have become plentiful and cheap in the U.S. and other developed nations. At the same time (thanks again to technology), physical exertion is no longer a part of most people's lives; most of us have to drag ourselves away from our computer or TV to burn off the excess calories. The result is inevitable. In 1950 one-quarter of Americans were classified as overweight; today half are.

And despite the harangues of medical experts, who constantly point out that obesity can lead to diabetes, heart disease and high blood pressure, that's not likely to change. We'll keep getting fatter and fatter, with no real prospect of reversing the trend.

Unless medical science provides a quick fix, that is. So far, the record on diet pills has been pretty dismal. Amphetamines, which speeded metabolism and suppressed appetite, looked promising in the 1950s and '60s but turned out to be physically harmful and powerfully addictive. Drugs like fen-phen and Redux, which alter the brain's chemistry, had scary side effects. Newer drugs like orlistat and food substitutes like olestra keep fat from entering the body, but they cause serious bowel discomfort.

Researchers are learning more every day about how the body processes fat. One clue involves the hormone leptin, which is pumped out by fat cells and signals lab mice, at least, not to eat. Unfortunately, as reported last week in the Journal of the American Medical Association, it doesn't seem to work in humans. Researchers are still trying to figure out why not--and how to get around the problem. Another natural substance, called pro-opiomelanocortin (POMC), seems to signal that it's time to stop eating. Mice treated with POMC boosters shed 40% of their excess body weight in just two weeks. Again, it's not clear that this will work in humans, but it's conceivable that POMC therapy--perhaps in shots--could someday be standard.

Scientists are also focusing on the differences between two types of fat cells, known as brown and white. The former, active in young mammals (including humans), convert fat into heat rather than storing it. That's crucial in newborns, whose temperature-regulation systems aren't fully formed. As we age, the brown cells become inactive and the white, which convert dietary fat to body fat, take over. Several research teams have found that by reactivating the brown cells in an adult animal with medication, they can burn off fat dramatically. Now the doctors are looking for a genetic switch that can do the same for humans.

What's becoming clear to scientists in the obesity business is that the body's energy-processing system involves not one or two but a maze of metabolic pathways. POMC, leptin and brown fat cells are part of the story. But nerve cells have also been implicated in weight regulation, and it's not clear how these different pathways relate to one another. "Not a month goes by," says Dr. Eric Ravussin, director of endocrine research at Eli Lilly, "without publication of a new pathway that regulates feeding behavior, giving us new potential targets."

Untangling this metabolic mess will probably take decades. But given the immense profits waiting for whoever can invent a safe, effective weight-control substance, drug companies aren't waiting. With the clues they have in hand, pharmaceutical firms are now investigating about 60 compounds, most of them based on some of the 130 genes that have so far been implicated in weight control.

So it seems likely that for a while at least we'll keep getting fatter. We can't undo evolution, and we haven't found a way to fool Mother Nature--yet. But before the 21st century is half over, with the body's fat-centric metabolism laid bare and the ability to manipulate genes part of medicine's standard tool kit, the trend may finally stop. Chubbiness may not disappear, but it could become optional. A future without Richard Simmons' commercials would be a wonderful future indeed.

--Reported by Alice Park/New York

TIME senior writer Michael D. Lemonick is the author of The Light at the Edge of the Universe and Other Worlds

[SIZE]

HEADING FOR SIZE 14 1975 NOW 2025

Weight of an average American woman 116 to 124 to 145 to 131 lbs. 148 lbs. 169 lbs.

Percentage who are overweight 25% 47% 75%

Source: Dr. George Blackburn, N.A. Assoc. for the Study of Obesity

With reporting by Alice Park/New York