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Q. How does leptin affect weight

"Here's the question: If this thing works like a thermostat -- an adipostat -- why do we keep gaining weight?" Lustig says.

The problem is that overweight people have large amounts of leptin, but their brains aren't getting the important signal to stop eating.

"How come the brain doesn't get it? That phenomenon is called ‘leptin resistance,'" says Lustig, who has done research on the subject. Leptin resistance is similar to insulin resistance in type 2 diabetes, in which the pancreas produces large amounts of insulin, but the body doesn't respond to it properly.

Leptin levels can keep going higher as people get fatter. "We all have a leptin floor; the problem is, we don't have a leptin ceiling," Lustig says.

"In leptin resistance, your leptin is high, which means you're fat, but your brain can't see it. In other words, your brain is starved, while your body is obese. And that's what obesity is: it's brain starvation."

Not only is leptin part of the hunger system, it's also part of the reward system, Lustig says. "When your leptin levels are low, food is even more rewarding. When your leptin levels are high, that's supposed to extinguish the reward system so that you don't need to eat so much, and food doesn't look nearly as good."

But in leptin-resistant people, the reward system doesn't cue a person to stop eating when leptin levels rise, Lustig says. "The leptin is being made by the fat cells, the fat cells are trying to tell the brain, ‘Hey, I don't need to eat so much,' but the brain can't get the signal. You feel hungrier and the reward doesn't get extinguished. It only gets fostered, and so you eat more and you keep going and it becomes a vicious cycle. If your brain can't see the leptin signal, you're going to get obese."

Q. Can leptin work as an obesity treatment?

That was the great hope after leptin's discovery in 1994, says Richard Atkinson, MD, an endocrinologist, obesity expert, and clinical professor of pathology at Virginia Commonwealth University.

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