Smokers tend to die young, but they tend to die thinner than non-smokers. A team of scientists led by Yale School of Medicine has discovered exactly how nicotine suppresses appetite – findings that suggest that it might be possible to develop a drug that would help smokers, and non-smokers, stay thin.

Nicotine activates a small set of neurons in a section of the hypothalamus that signals the body has had enough to eat, the researchers report in the June 10 issue of the journal Science. Nicotine accomplishes this trick by activating a different set of receptors on the surface of neurons than those that trigger a craving for tobacco.

"Unfortunately, smoking does keep weight off," said Marina Picciotto, the Charles B.G. Murphy Professor of Psychiatry, professor of neurobiology and pharmacology and senior author of the paper. "Many people say they won't quit smoking because they'll gain weight. 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."

Picciotto is an expert on the function of nicotine receptors located on the surface of neurons. Nicotinic acetylcholine receptors have many functions, and in the brain are the primary targets of nicotine. Yann Mineur, an associate research scientist in her lab, was investigating a potential drug for depression that acts upon these receptors when he noticed that mice given the drug ate less than those not on the medication. With the help of researchers at Carleton University in Ottawa and the University of Hawaii, they decided to investigate why.

In a variety of experiments, the researchers found that the experimental drug activated a specific type of nicotine receptor, which in turn activated the subset of neurons in the hypothalamus, called pro-opiomelanocortin or POMC cells. The team also found that when subjected to nicotine, mice lacking the POMC pathway did not lose weight, unlike mice with the pathway intact. Intriguingly, they also showed that these receptors were of a different type than those known to trigger tobacco craving in smokers.

"This suggests it is possible to get the effect of appetite suppression without also triggering the brain's reward centers," Picciotto said. Baylor College of Medicine contributed to the study. Other Yale authors are Yan Rao, Ralph J. DiLeone, Sabrina Diano, Tamas L. Horvath and Xiao-Bing Gao.