4:52pm

Thu June 9, 2011
Research News

The Skinny On Smoking: Why Nicotine Curbs Appetite

Originally published on Fri June 10, 2011 4:13 am

Scientists say they have finally figured out how smoking helps people keep off extra pounds.

It turns out that nicotine activates a pathway in the brain that suppresses appetite, according to a study in the journal Science. This discovery should lead to better diet drugs, the researchers say.

The finding comes after decades of research showing that smokers tend to be a bit thinner than nonsmokers, and that smokers who quit tend to put on weight.

Researchers made the discovery after stumbling onto a major clue recently, says Marina Picciotto, a professor of psychiatry at Yale and one of the study's authors.

The clue turned up during experiments looking for chemicals to treat depression, Picciotto says. A scientist at Yale named Yann Mineur was giving mice a chemical that's a lot like nicotine, she says.

"He was watching these mice and he said, 'You know what, they don't eat as much as the mice that didn't get this medication,' " she says. "And so he decided to follow that up. It was a window into how nicotine might be decreasing appetite."

The scientists knew that nicotine must be triggering a response in certain brain cells. So they started looking at cells in the hypothalamus, a part of the brain known to regulate appetite. And they focused on a type of nerve cell, called POMC cells, known to be involved in eating behavior.

Sure enough, nicotine made these POMC cells more active. But the researchers still needed to figure out how nicotine was communicating with these cells.

To find out, the team took a closer look at the different types of receptors on the surface of the cells, Picciotto says.

"And we actually thought that maybe the same nicotine receptors that make you want to smoke, that make you rewarded when you smoke, would be the ones that also control appetite," she says. "But we were wrong."

So the team looked at another type of receptor. These receptors don't make you feel good — they're involved in the so-called fight-or-flight response that occurs when animals or people encounter a threat.

It turned out these fight-or-flight receptors responded to nicotine in a way that reduced hunger. That would make sense from an evolutionary perspective, Picciotto says.

"The fight-or-flight response is one where you actually want to preserve your energy to do something very important," she says. "So maybe you don't want to be out there eating while you're supposed to be running away from a tiger."

The nicotine research does not mean people should take up smoking to lose weight, Picciotto says. But for people who already smoke and want to quit, but don't want to put on weight, she says, nicotine gum or a patch might help.

Still, Picciotto says, any form of nicotine has a downside, and scientists who study weight loss agree.

If people used, say, a nicotine patch, "you might find that patients do lose weight but then become dependent on a patch all the time," says Michael Cowley, who directs the Obesity and Diabetes Institute at Monash University in Melbourne, Australia.

Fortunately, Cowley says, Picciotto's new research hints at a much better solution: drugs that suppress appetite without triggering the brain circuits involved in addiction.

"What this shows is that there's a whole new class of drugs that can potentially be used as weight-loss agents," Cowley says.

Picciotto's lab has already shown that a nicotine-like chemical called cytisine causes mice to eat less.

Cytisine comes from a natural source: the laburnum plant, a flowering shrub found in Eastern Europe, Picciotto says. She says it's sold there as an herbal smoking cessation product.

Copyright 2013 NPR. To see more, visit http://www.npr.org/.

Transcript

MELISSA BLOCK, host:

This is ALL THINGS CONSIDERED from NPR News. I'm Melissa Block.

MICHELE NORRIS, host:

And I'm Michele Norris.

Smoking is a pretty risky way to control your weight, but it can work. Studies show that smokers tend to be a bit thinner than nonsmokers. And now scientists think they've figured out why.

NPR's Jon Hamilton reports on an accidental discovery that could lead to safer diet drugs.

JON HAMILTON: Most smokers know that tobacco can suppress hunger, like the young woman lighting up a Virginia Slim outside this bar in Washington, D.C.

Ms. ANN-MARIE VANTASSELL: My name is Ann-Marie Vantassell. I'm a bartender-server at the Red Derby here in Columbia Heights.

HAMILTON: Vantassell is 24. She smokes during her breaks. And she's thin.

Ms. VANTASSELL: I mean I think everyone knows, look, this is terrible, but I do this. I need to stop, but I can't stop. And then, yeah, I mean, I have tried to quit, and I have noticed I do eat a lot more, and, you know you might gain a little weight: Like, oh, might as well just keep smoking.

(Soundbite of laughter)

HAMILTON: Vantassell says she has no idea how nicotine affects a person's appetite. And scientists were puzzled too, until a few months ago when researchers at Yale stumbled upon a major clue.

Marina Picciotto says they were studying chemicals to treat depression. Picciotto says a scientist named Yann Mineur was giving mice something a lot like nicotine.

Ms. MARINA PICCIOTTO (Yale University): He was very, very good as a scientist. He was watching these mice, he said: You know what? They don't eat as much as the mice that didn't get this medication. And so he decided to follow that up. It was a window into how nicotine might be decreasing appetite.

HAMILTON: The scientists knew that nicotine must be triggering a response in certain brain cells. So they started looking at cells in the hypothalamus, a part of the brain known to regulate appetite. And they focused on a type of cell involved in eating behavior. Sure enough, nicotine made these cells more active.

But how was nicotine communicating with them? Picciotto says to find out, they took a closer look at the different types of receptors on the surface of the cells.

Ms. PICCIOTTO: And we actually thought that maybe the same nicotine receptors that make you want to smoke, that make you rewarded when you smoke, would be the ones that also control appetite. But we were wrong.

HAMILTON: So they looked at another type of receptor. These receptors don't make you feel good; they're involved in the so-called fight-or-flight response when you're faced with, say, a tiger. It turned out these fight-or-flight receptors responded to nicotine in a way that reduced hunger. Picciotto says from an evolutionary perspective, that makes sense.

Ms. PICCIOTTO: The fight-or-flight response is one where you actually want to preserve your energy to do something very important. So maybe you don't want to be out there eating while you're supposed to be running away from a tiger.

HAMILTON: Picciotto says her research does not mean you should take up smoking to lose weight: think lung cancer or a heart attack. But she says if you already smoke and want to quit but don't want to put on weight, nicotine gum or a patch might help.

Still, Picciotto says, any form of nicotine has a downside. And scientists who study weight loss agree. Michael Cowley directs the Obesity and Diabetes Institute at Monash University in Melbourne, Australia.

Mr. MICHAEL COWLEY (Director, Obesity and Diabetes Institute, Monash University): If you were to develop, say, a nicotine patch, as we have, and use that for weight loss, you might find that patients do lose weight but then become dependent on a patch all the time.

HAMILTON: Cowley says Picciotto's new research hints at a much better solution: drugs that suppress appetite without triggering the brain circuits involved in addiction.

Mr. COWLEY: What this shows is that there's a whole new class of drugs that can potentially be used as weight-loss agents, particularly molecules that mimic nicotine a little bit.

HAMILTON: But aren't addictive. Picciotto says her lab has already experimented in mice with a promising natural substance called cytisine.

Ms. PICCIOTTO: It's found in the Laburnum plant, which is a flowering shrub, and it turns out that this chemical is used in Eastern Europe for an herbal smoking cessation remedy.

HAMILTON: The new study appears in the journal Science. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.