Experts Try to Trim Hype on Fat Hormone
Arguably no trend is easier to predict than the future craze for leptin, the newly discovered hormone that regulates body fat so dramatically that obese laboratory mice given injections of it shed a third of their weight in two weeks.
The obese mice, weighing three times the norm--comparable to a 500-pound man--were born with a genetic defect that kept them from producing the hormone. In studies conducted in three laboratories, obese mice that received leptin injections soon started eating less, moving around more, generating more heat, and otherwise adjusting their thermostats to burning fat. Also, researchers have discovered that normal mice injected with leptin lost some fat.
Those findings, announced two weeks ago, were hailed and hyped nationwide, offering new evidence for the widespread hope that being fat is not the result of too much of a good thing, but too little.
And with a vividness that few novelists and historians muster, the scientific research helps explain a modern American dilemma, what might be called the Predicament of Plenty. The voracious appetite and fat-grabbing metabolism of human beings, biologists say, evolved eons ago, when famine was a constant threat and making the most of every hard-won morsel made good physiological sense. But now a pizza is never more than a phone call away, and our extraordinary ability to store calories as fat seems a curse.
It has long been assumed that science’s ultimate contribution to gustation was going to be the meal-in-a-pill. According to that sci-fi scenario, people in the future would be too busy to eat and too intellectual to miss doing so.
Now we know that that was a vision only a brainiac could love. To judge from the interest in leptin, what people really want is a meal-on-a-plate, followed by a pill that lets them have dessert.
But that updated scenario creates nearly as many problems as it would appear to solve, researchers say. Scientists, psychotherapists and others are debating the possible uses and abuses of a powerful hormone that shows promise of hastening the disappearance of humanity’s least popular tissue.
Barbara J. Moore, nutritionist and executive director of Shape Up America, a public health education campaign, said the leptin hubbub is something of a red, if not creamed, herring. “One of the things we’re concerned about is that people are waiting for science to catch up with their fantasies about a fat-reducing drug that works while they’re sitting on the couch watching TV,” she said.
Moore said most people are overweight “for simple, non-genetic reasons”: They eat too much and move around too little. If a powerful leptin-like drug discouraged them from exercising, she added, it could be harmful in the long run. Users would lose out on the many benefits of physical activity, such as better heart function and higher self-esteem. “Even if science does catch up with their fantasies,” she said, “they’ll be selling their health down the drain.”
Psychotherapists suggest that giving chronically obese people a leptin-like drug would be something like forcing anorexic people to eat banana splits: The body might change, but the underlying urge or discontent would remain untouched.
“I’m afraid of abuse” of leptin, said Deena Solomon, a cognitive therapist in Santa Monica, who counsels people with eating disorders. She said she thinks of an obese person’s fat as evidence of a skewed “coping strategy”--roughly, when the going gets tough, food equals comfort. “What terrifies me,” she said of the possibility of a leptin drug, “is that it’s a way of getting rid of the evidence without addressing the coping strategy.”
And because this hypothetical leptin drug would also be attractive to people who were merely a few pounds overweight, some observers see an ominous trend in which high-tech medicine serves the god of human vanity on a scale unimagined by even the most zealous plastic surgeon.
“We’re getting to the point with our biological sophistication that we’re going to start taking people who are healthy and trying to make them even better,” said Dr. John D. Lantos, a pediatrician and medical ethicist at the University of Chicago. “That’s a whole new field for medicine.”
Offering a sort of Thin New World scenario, Hillel Schwartz, author of “Never Satisfied,” a history of dieting and body image in America, worried that a powerful, widely available thinning drug could make pariahs of obese people. Long cast out for being judged indulgent or lazy, now they would be shunned for refusing to take their medicine.
“There is great fear that this could become a kind of socially compulsory drug for fat people to take,” Schwartz said. “If this becomes available, people will say, ‘Well, there is no reason for you to be fat.’ ”
According to studies in several labs, people also produce leptin. Amgen, a Torrance-based biotechnology company, holds an exclusive patent to develop leptin products, and is producing the human hormone in genetically engineered bacteria. While a lot can happen to nix the best-laid plans, Amgen hopes to begin testing the hormone in people as soon as next year.
But leptin’s discoverer, Jeffrey Friedman, a molecular biologist at the Howard Hughes Medical Institute and Rockefeller University in New York, pointed out that leptin is far from ready for prime time. “The next critical step is to see if it’s safe in animals.” He added, “You can’t contemplate giving anything to humans until those safety concerns are met.”
Before leptin reaches the public, laboratory and clinical experiments will first have to show that it works in people and is safe. Only then could it possibly win Food and Drug Administration approval.
One group is unlikely to wait for government approval to get its slice of the leptin pie: the diet hucksters.
Americans spend $30 billion a year trying to get slim, or at least appearing to, because that figure includes not only weight-loss clinic fees but low-cal sodas, Lycra exercise shorts and other accouterments of the light lifestyle. Given that bonanza, it seems that leptin is ripe for exploitation. “Con artists always leap on new science to try and sell scam products,” said Dr. Victor Herbert, a nutritionist and authority on medical fraud at the Bronx Veterans Affairs Medical Center in New York.
What happened with the prescription acne drug Retin-A is instructive. Shortly after researchers announced that it also reduced fine skin wrinkles, demand skyrocketed and fly-by-night firms capitalized by selling bogus products with sound-alike ingredients such as “Retinyl-A.”
Similarly, Herbert agreed, one can imagine an enterprising firm developing a weight-reducing product with the miracle ingredient “leptron” or “leptix” or something else calculated to confuse. Clinics and posh spas also may try luring customers with “leptin” treatments, whether or not they bother obtaining the real thing. “That’s the history of quackery--turning science into pseudoscience,” he said.
It attests to Americans’ faith in biomedicine, never mind their longing for flat tummies, that so much worry and excitement has been inspired by a mouse built like a tennis ball that is perpetually eating what it believes to be its last meal.
Ironically, explained Stephen K. Burley, a biochemist also at the Howard Hughes Institute and Rockefeller University, these lab-bred leptin-lacking obese mice, called ob/ob, “actually behave as though they’re starving.” No matter how much the mice eat, Burley said, their appetites rage.
As far as Friedman and Burley can tell, leptin is secreted by fat cells, and then travels the bloodstream to brain centers that control appetite, fat storage and fat breakdown. The name leptin, which won’t be official nomenclature until accepted by a scientific panel, is from the Greek word for thin.
Dr. Jose Caro, a metabolism specialist at Thomas Jefferson University in Philadelphia, said that all of the 160 obese people he has checked appear to have a functioning leptin gene.
If leptin plays a role in human obesity, the matter is more complex than a simple lack of the hormone, Caro said. Out of 60 people whose genetic material Caro has closely analyzed, three--5%--had a slightly mutated form of the leptin gene. They may produce a somewhat different, perhaps less efficient, version of the leptin molecule--rather like a key that fits a lock but still doesn’t turn the cylinder.
Or, researchers speculate, some obese people may have a genetic defect in the cellular structures that are meant to receive leptin’s message--a glitch in the lock itself, as it were. By thus preventing leptin’s message from being accepted, a defective receptor may also predispose one to obesity.
A direct analogy is type II diabetes, which occurs in spite of adequate natural insulin because of a defect in the insulin receptors on the surface of cells. And just as type II diabetes can be treated with massive doses of insulin, essentially overwhelming the reluctant receptors, scientists believe that a person with defective leptin receptors may also be treated with massive leptin doses.
Caro said it is crucial to understand “fat genes,” but added that the “fat environment” is even more important.
The percentage of fat Americans is twice as high today as in 1900, Caro said, and the reason is not that our gene pool has changed drastically. The difference, Caro said: “Your grandmother grew up in a lean environment. You live in an obese environment.”
He recently had an experience akin to time travel that drove that point home nicely. While visiting rural Colorado, he rode horses and bicycles, hiked and didn’t once step into a 7-Eleven. “A lean environment,” he called it.
Then, passing through the Denver airport, he was struck by the moving sidewalks that rolled by one snack bar after another. “An obese environment,” he said.
Linda Webb Carilli, spokeswoman for Weight Watchers International, was similarly disinclined to look at obesity genes and the discovery of leptin out of context.
“I don’t think of obesity as a nutrition problem,” she said. “I think of it as a social problem. How many other countries have restaurants with all you can eat for $9.95?”
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The Leptin Top 10
Hearing for the first time about leptin, the newly found hormone that got genetically obese mice to shed a third of their fat in two weeks, many Americans had just one question: Where can I get it?
Answer: Nowhere.
To be sure, leptin has not been tested on people, though it may be as soon as next year. Meanwhile, health experts are raising questions about the much-hoped-for-but-still-hypothetical human obesity treatment.
Here, with apologies to Mr. Letterman, are the Top 10:
10. How does it work? Though scientists suspect that leptin is secreted almost exclusively by fat cells, they say they don’t know how it passes along its chemical message to the brain.
9. Is it safe in animals? Until scientists test it for longer than a month, they can’t rule out toxic side effects.
8. Does it work in people? The multi-multimillion-dollar question.
7. Could it possibly work as dramatically in people as in the lab animals? Doubtful. Unlike the monster mice, virtually all people tested so far produce some leptin of their own. Then again, normal mice injected with leptin lost some fat.
6. Is it safe in people? This is a crucial question because people might have to take it for years.
5. Will the Food and Drug Administration approve its use? Not until it is shown to be safe and effective.
4. If it passes muster, will it be affordable? Genetically engineered drugs aren’t cheap.
3. Will it always be a drug that has to be injected? A pill seems unlikely, since the digestive system may break leptin down.
2. What does it say about human beings that we seem willing to spend a fortune repeatedly injecting ourselves with a powerful drug in order to lose pounds of flesh that would disappear if we simply moved more and ate less? It isn’t pretty.
1. How are diet hucksters likely to make you lose weight with leptin? By selling bogus “leptin” that lightens your wallet.
