Nicotine Suppresses Appetite by Binding Receptors in the Hypothalamus

A new study that identifies critical molecular and synaptic mechanisms involved in nicotine-induced decrease in appetite suggests it may be possible to develop drugs to help quitters stop gaining weight when they give up smoking.

Researchers at Yale School of Medicine (Yale; New Haven, CT, USA) and Baylor College of Medicine (Houston, TX, USA) using a combination of pharmacological, molecular genetics, electrophysiological, and feeding studies in mice, found that activation of hypothalamic α3β4 nicotinic acetylcholine receptors leads to activation of pro-opiomelanocortin (POMC) neurons. The POMC neurons and the subsequent activation of melanocortin 4 receptors were found to be critical for nicotinic-induced decreases in food intake in mice.

The researchers also showed that when given nicotine, mice that did not have the POMC pathway did not lose weight, whereas those, whose POMC pathway was still intact, did lose weight. These particular receptors were not the same as those known to trigger tobacco craving in smokers; according to the researchers, this means it may be possible to effect appetite suppression without triggering the reward centers in the brain. In fact, 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 blocked cytisine from binding to the receptor stopped the reduction in food intake. The study was published in the June 10, 2011, issue of Science.

"We found that nicotine reduced eating and body fat through receptors implicated in nicotine aversion and withdrawal rather than reward and reinforcement," said senior author Marina Picciotto, MD, PhD, a professor of neurobiology and pharmacology at Yale. "Ultimately, we would like to help people maintain their body weight when they kick the habit and perhaps help nonsmokers who are struggling with obesity."

Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6% - 3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves. In low concentrations (an average cigarette yields about 1 mg of absorbed nicotine), the substance acts as a stimulant in mammals, and is the main factor responsible for the dependence-forming properties of tobacco smoking. Nicotine content in cigarettes has slowly increased over the years, and one study found that there was an average increase of 1.6% per year between the years of 1998 and 2005; this was found for all major market categories of cigarettes.

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