A discovery of precisely how nicotine suppresses appetite, suggests it may be possible to develop drugs that help people stop gaining weight when they give up smoking, something that puts many smokers off quitting, according to a new study published online this week in the journal Science. The scientists discovered a brain pathway in mice that could be the target of new drugs for smoking cessation and weight control without triggering a craving for tobacco.
Previous studies have shown that although on average people gain no more than 10 lbs (4.5 kg) in weight when they give up smoking, the fear of weight gain is often what discourages some smokers from quitting
Previous studies have shown that although on average people gain no more than 10 lbs (4.5 kg) in weight when they give up smoking, the fear of weight gain is often what discourages some smokers from quitting
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Led by Yale School of Medicine, the research team found that a specific type of brain nicotine receptor in the hypothalamus, a brain center that controls feeding, allows nicotine to reduce food intake in laboratory mice.
(A receptor is a "gatekeeper" molecule that sits on the surface of cells and only allows a matching chemical - in this case nicotine - to activate specific instructions for cells to do things.)
In this study, the researchers found that nicotine activates a different set of receptors on the surface of brain cells to those that trigger a craving for tobacco.
Senior author Dr Marina Picciotto, the Charles B.G. Murphy Professor of Psychiatry, and professor of neurobiology and pharmacology at Yale School of Medicine, told the press that:
"We found that nicotine reduced eating and body fat through receptors implicated in nicotine aversion and withdrawal rather than reward and reinforcement."
"Ultimately, we would like to help people maintain their body weight when they kick the habit and perhaps help non-smokers who are struggling with obesity," said Picciotto.
Picciotto and colleagues showed that nicotine activated a specific type of nicotine receptor located on pro-opiomelanocortin or POMC cells, a specific subset of neurons in the hypothalamus.
They also showed that when given nicotine, mice that did not have the POMC pathway did not lose weight, whereas mice whose POMC pathway was still intact, did lose weight.
Plus, they found that these particular receptors were not the same as those known to trigger tobacco craving in smokers.
Picciotto said this means it may be possible to get the effect of appetite suppression without triggering the reward centers in the brain.
"We found that nicotine reduced eating and body fat through receptors implicated in nicotine aversion and withdrawal rather than reward and reinforcement," she said.
A nicotine-like drug, cytisine, also had the same effect: it specifically activated the nicotinic receptors in the hypothalamus, leading to reduced food intake and body fat in the mouse model. The effect was very specific, since a drug that stopped cytisine from binding to the receptor stopped the reduction in food intake.
So far this effect has only been shown in mice. More needs to be done to prove that these pathways behave in the same way in humans, and that it is possible to achieve the same selective effect with nicotine-like drugs in humans.
Dr Nora Volkow, Director of the National Institute on Drug Abuse, part of the National Institutes of Health, which funded the study, said:
"These results indicate that medications that specifically target this pathway could alleviate nicotine withdrawal as well as reduce the risk of overeating during smoking cessation."
"Although more research is warranted, such a highly selective compound might be more effective than drugs that act on more than one type of nicotinic receptor," she added.
Led by Yale School of Medicine, the research team found that a specific type of brain nicotine receptor in the hypothalamus, a brain center that controls feeding, allows nicotine to reduce food intake in laboratory mice.
(A receptor is a "gatekeeper" molecule that sits on the surface of cells and only allows a matching chemical - in this case nicotine - to activate specific instructions for cells to do things.)
In this study, the researchers found that nicotine activates a different set of receptors on the surface of brain cells to those that trigger a craving for tobacco.
Senior author Dr Marina Picciotto, the Charles B.G. Murphy Professor of Psychiatry, and professor of neurobiology and pharmacology at Yale School of Medicine, told the press that:
"We found that nicotine reduced eating and body fat through receptors implicated in nicotine aversion and withdrawal rather than reward and reinforcement."
"Ultimately, we would like to help people maintain their body weight when they kick the habit and perhaps help non-smokers who are struggling with obesity," said Picciotto.
Picciotto and colleagues showed that nicotine activated a specific type of nicotine receptor located on pro-opiomelanocortin or POMC cells, a specific subset of neurons in the hypothalamus.
They also showed that when given nicotine, mice that did not have the POMC pathway did not lose weight, whereas mice whose POMC pathway was still intact, did lose weight.
Plus, they found that these particular receptors were not the same as those known to trigger tobacco craving in smokers.
Picciotto said this means it may be possible to get the effect of appetite suppression without triggering the reward centers in the brain.
"We found that nicotine reduced eating and body fat through receptors implicated in nicotine aversion and withdrawal rather than reward and reinforcement," she said.
A nicotine-like drug, cytisine, also had the same effect: it specifically activated the nicotinic receptors in the hypothalamus, leading to reduced food intake and body fat in the mouse model. The effect was very specific, since a drug that stopped cytisine from binding to the receptor stopped the reduction in food intake.
So far this effect has only been shown in mice. More needs to be done to prove that these pathways behave in the same way in humans, and that it is possible to achieve the same selective effect with nicotine-like drugs in humans.
Dr Nora Volkow, Director of the National Institute on Drug Abuse, part of the National Institutes of Health, which funded the study, said:
"These results indicate that medications that specifically target this pathway could alleviate nicotine withdrawal as well as reduce the risk of overeating during smoking cessation."
"Although more research is warranted, such a highly selective compound might be more effective than drugs that act on more than one type of nicotinic receptor," she added.
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