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Why fat people are hungrier

Like all people who are "a bit" overweight, I am fascinated by any scientific advance that even hints at a way to solve the problem -- by which I mean some kind of magic anti-fat pill that I can take and become slim, without the bother of dieting. I've tried dieting, and all I've lost is confidence. In a column about fad diets I wrote a few months ago, "Searching for an easy way to loose weight," I argued that there is no easy way -- just eat less, exercise more, and keep at it. But, being human and imperfect, I find I cannot help hoping.

My hope has centered on a hormone called leptin. Leptin was discovered in 1994 by a researcher named Jeffrey Friedman. Friedman was investigating how your body regulates its appetite. He found that a hormone he called leptin is produced in the adipose (fat) cells that store the body's fat reserves. This hormone acts as a simple feedback signal. When ample fat is present in your body's adipose cells, they produce leptin. The leptin is carried via the bloodstream to the portion of your brain called the hypothalamus, the brain's appetite center. Leptin turns off the "I'm hungry" signal emitted by the hypothalamus, reducing your desire to eat.

You can understand my fascination with leptin. Maybe its not my fault after all. Maybe I'm overweight not because I eat too much, but simply because I don't manufacture enough leptin! Just give me a leptin pill and I could return to the svelte 165 I weighed the day I married.

Unfortunately, things aren't that simple. "Anti-fat" leptin pills have been tried on obese people, and they don't seem to work. It turns out that these people are not overweight because they are not producing leptin. They have fully functioning leptin systems, and their appetite regulation systems function perfectly. So how come overweight people like them -- and me -- still have such an urge to eat?

The answer became clear with experiments reported in July by Luciano Rossetti and his colleagues at the Albert Einstein College of Medicine in New York. It turns out your body adjusts its propensity to produce leptin to suite its expectations. Not only does your hypothalamus learn from leptin how much fat your cells contain now, it also learns how much you expect to get in the future. Humans evolved, like other animals, in a world where food was scarce, and we are biologically programmed to treat it as a precious commodity, to be consumed aggressively when available. If your body thinks there is abundant food to be had, it will adjust its appetite upward to encourage you to consume more.

To learn about human appetite, Rossetti studies rats. This isn't unusual. Dietary experiments on human eating patterns are expensive and difficult to do, and rats seem to run their bodies much as we do. Rossetti set up two groups of laboratory rats. In group 1, the rats were allowed to eat all they wanted for three days. They ate a lot. We'll call this group the "overeaters." In group 2, the rats were restricted to eating half of what the first group had consumed. We'll call this group the "restricted eaters."

After the three day eating period, the two groups of rats were injected with leptin. Rossetti then looked to see what this jolt of leptin did to the rats' own leptin production. Normally, such an injection of leptin would reduce the animal's leptin production. Sensors in the fat cells that manufacture the leptin would detect excessive leptin levels, and reduce production accordingly.

In this case, however, that is not what happened. Instead, the "restricted eaters" did not reduce leptin production in their fat cells. The sensors in their fat cells simply ignored the added leptin and kept on making leptin at the regular rate. The extra leptin added by researchers did not change the relation between fat and leptin production in the rats' adapose tissue, so it increased their appetites only transiently.

The "overeaters," on the other hand, reduced the amount of leptin they produced. That means that, unlike a poorly fed rat, a fat rat's appetite is still able to increase. Researchers were able to trick their adipose tissue into decreasing the amount of leptin produced for a given amount of fat -- increasing their appetite!

Why would fat rats want to eat more than slimmer ones? Apparently the leptin system adjusts rapidly to the dietary environment. In just three days of binging, the "overeaters" learned to accommodate to a richer life. Expecting good times to go on, their fat tissue downgrades its leptin production to maximize food consumption and fat storage. Soon, despite their binging, they will be hungry and want to go out and seek more food. This makes perfectly good evolutionary sense if you think of food as a scare resource. They are simply making hay while the sun shines.

The poorly fed "restricted eaters," by contrast, will expect little in the way of food, and feel sated with the food they are able to get. From an evolutionary point of view, there is little sense in wasting energy in searching for food that isn't there. If food is available, a sensible animal will hoard it. If not, better to stop worrying about eating and get on with the business of living.

At first I was discouraged, learning that there is not going to be an "anti-fat" leptin pill. Then I brightened up. Look at the slim rats, I told myself, not the fat ones. They reduced their appetites by not overeating. If a rat can do it, so can I.

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