Recent findings from two different publications reveal parts of this mechanism, but while most reports have pin-pointed the results involving appetite suppression through pro-opiomelanocortin neurons, there is evidence that the complete picture is more complicated than that.
The neural and endocrine substrates of appetite and hunger form an intricate web of counteracting hunger and satiety signals that give each other feedback at different levels. Add to that the cognitive neural substrates of motivation and it becomes very apparent that simply getting us to eat, or stop eating for that matter, is a very complex task for the brain. Central to this task though, is a group of neurons in the arcuate nucleus of the hypothalamus that contain the peptide pro-opiomelanocortin, or POMC. These neurons are essentially an "off button" for appetite, initiating the second-order signals in the brain that reduce hunger and food intake. They are sensitive to circulating levels of leptin and insulin, which are higher after meals.
Until recently it remained unknown if this central regulation of appetite was the neural substrate for the effect of nicotine on body weight, even though it was a likely hypothesis. A recent article in Science headed by researchers from the Yale University School of Medicine (ref. 1 below) details a series of very elegant experiments showing that nicotinic drugs can activate these POMC neurons and reduce food intake in mouse models. As a part of this, the researchers demonstrated that POMC neurons express nicotinic receptors, nACHRs, and that these receptors were likely behind the observed reduction in food intake. Of course the nicotinic receptors don't normally respond to nicotine, which is an external substance, but to the signal substance acetylcholine. The finding that nicotinic acetylcholine receptors are expressed on POMC neurons adds a new level to the regulation of appetite. You can read more about the experiments and some of the specific results at Ars Technica or 80beats.
This work is beautifully done, not only because it reveals a central mechanism, but also because it has possible future applications in medical intervention to prevent weight gain in smokers who want to quit, and perhaps also in obesity treatment. Most media reports of this finding have taken up this perspective. See for instance the reports at NPR and TIME.com.
Understanding the link between nicotine and satiety, for example, could lead to new drugs that target the nicotine receptors on appetite-controlling cells, giving smokers a way to quit without the weight gain. <...>
"If we had a medicine targeted at these receptors, then people who are not quitting smoking because they are afraid of gaining weight now might make the attempt," Picciotto says. "That's a really exciting area of drug development."
Even if such medicines were to prove effective, however, they may come with side effects. The nicotine receptors that regulate fullness and appetite are also closely linked to the body's fight-or-flight stress response, in which the body revs itself up in the face of a threat. Activating these receptors could lead to increased blood pressure and heart rate, which may not be a good thing for anyone.
However, most reports of these findings are not providing a perspective on how complex appetite and feeding regulation is. Rather than nicotine affecting only one neural substrate, it's likely that nicotine affects the whole network of hunger and satiety signals.
Similar research, published practically simultaneously in the June issue of the Journal of Neurophysiology (ref. 2 below) and curiously also by researchers from the Yale University School of Medicine, leads us in that direction. The researchers found that acetylcholine neurons are indeed present in the mouse arcuate nucleus and that nicotine is indeed able to activate the POMC neurons. But they also found that nicotine can activate other neurons in the arcuate nucleus that stimulate appetite and food intake, although to a lesser degree. These neurons release the neuropeptide NPY, affecting some of the same second-order signals as the POMC neurons. So NPY neurons can be seen as the corresponding "on button" to the POMC neurons' "off button", and nicotine seems to stimulate both.
These findings highlights the fact that appetite regulation in the brain consists of an intricately balanced network of hunger and satiety signals, rather than a singular mechanism, and that nicotine affects this network at different points, finely shifting the balance towards decreased appetitive behavior and therefore lower body-mass.
(1) Mineur, Y., Abizaid, A., Rao, Y., Salas, R., DiLeone, R., Gundisch, D., Diano, S., De Biasi, M., Horvath, T., Gao, X., & Picciotto, M. (2011). Nicotine Decreases Food Intake Through Activation of POMC Neurons Science, 332 (6035), 1330-1332 DOI: 10.1126/science.1201889
(2) Huang, H., Xu, Y., & van den Pol, A. (2011). Nicotine excites hypothalamic arcuate anorexigenic proopiomelanocortin neurons and orexigenic neuropeptide Y neurons: similarities and differences Journal of Neurophysiology DOI: 10.1152/jn.00740.2010