A Lot To Lose: Mind Over Matter?

New Theories Point To Brain Chemistry

Joe Solimine is the first to admit, he's a man obsessed with food.

"Now I'm not really hungry when I get up in the morning," he tells 48 Hours, but as the day wears on it gets worse and worse and the appetite starts to build. And by the end of the day, I'm like a vampire looking for blood."

That obsession is a trait the 58-year-old insurance executive shares with his good friends John Pfieffer, a 38-year-old construction contractor, and Wall Street lawyer Bill O'Connor, 46.

They call themselves "The Three Amigos". And now, with each of them weighing in at around 300 pounds, Jim Axelrod reports, they're turning to New York obesity expert Dr. Louis Aronne.

Aronne has put Joe and John on a liquid diet to jumpstart their weight loss. It was not without drawbacks: "I had a dream of this fluffy cheese omelette," John says.

That John consistently craves so much food doesn't exactly surprise Aronne.

"It could be that John has a mutation of some receptor in his brain and so he can't sense fullness," the doctor says.

It's what many overweight people have been saying for years – that being heavy isn't their fault. And now, Aronne and other top researchers believe that obesity is indeed driven by genetics and a complex series of circuits in the brain.

"Over time, the body loses control of weight," explains Aronne. "And you just can't control your weight because you're not getting the right messages from your body telling you how much fat is stored."

Scientists believe the hormone leptin is a key player in this messaging system. Leptin, which is produced by fat cells, sends signals to the brain, telling it whether enough fat is stored in the body and if it's time to stop eating.

Dr. Rudolph Leibel of Columbia University, who has been studying obesity for more than 20 years, works with mice deprived of leptin who have gotten fatter and fatter - in a sense, to try to increase the signal to the brain that would tell the animal, 'I have enough fat.'

"This animal never gets the signal," he says. "So it just keeps eating and eating and eating, and getting bigger and bigger." He and other researchers suspect the same thing happens in humans.

So now the race is on to develop that "magic bullet" - medication that will manipulate those genetic tendencies, including the regulation of leptin. The hope is that not only will people lose more weight but they'll keep it off.

When much weight is lost, the doctors say, the body senses this and responds as if a person were starving to death. The body does things like increase appetite and slow down the metabolism in an effort to spark a weight gain.

Joe is familiar with that: "I can't discipline myself," he says, "because I start to eat like I'vgot a tip on a famine. You know, like 'hey. Joe, eat today 'cause tomorrow there might not be any food.'"

Both Aronne and Leibel believe that medication is the best tool to "trick" the brain into thinking the belly's had enough food. One such drug, the anti-depressant Meridia, is already widely prescribed for weight loss, though its effects are limited. Two other drugs have shown great promise in clinical trials: Axokine, another appetite suppressant, and Topamax, an anti-seizure drug already being used to treat epilepsy.

The "Three Amigos began their diets without medication but several weeks into it, Solimine's cravings got the better of him. He's taking Topamax, while following a part liquid, low-carbohydrate diet.

Pfieffer and O'Connor are sticking to their own low-carb diets, so far without the help of any drugs.

After two months of dieting, each lost 30 pounds. They are looking better and fitting into clothes they couldn't wear a few months ago. But the bottom line for all three is that life lasts longer, when it's lived a little lighter.

"I'd like to enjoy my grandchildren," says Solimine, to I've got to get my act together."

July 2002 Update:

Joe Solimine has lost 6-7 lbs since January. He's still on Topomax. John Pfieffer has lost 15 more lbs since January. Bill O'Connor has lost 30 lbs.

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