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The Facts on Leptin: FAQ

The truth about the hormone leptin and obesity.

Q. How does leptin affect weight continued...

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.

According to Atkinson, mouse experiments that began in the early 1970s pointed to "some sort of a hormone that affected food intake and body fat, but [scientists] didn't know what it was."

When researchers finally discovered leptin in 1994, it helped "put obesity on the map because it suggested…obesity may have some physiological basis, instead of just being, "fat people can't keep their mouth shut,'" Atkinson says. "For those of us in the field of obesity, it was a watershed moment. Suddenly, everybody jumped on the bandwagon. This became a frantic obsession with the obesity community, at least."

Many scientists explored leptin as a possible treatment for obesity; they believed that if people were leptin-deficient, giving them leptin would raise levels, which would signal them to stop overeating. "But when you started giving it to people, it didn't work so well," Atkinson says.

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