Despite the impressive gains in cardiovascular morbidity and mortality that have occurred over the past decades, a veritable elephant still exists in the room in the shape of the tidal wave of obesity sweeping the globe, which may reverse these advances.  Obesity has proved fundamentally difficult to manage, with few therapies demonstrating sustained weight loss over time be they pharmacological or behavioural.  Paradoxically, that other great modifiable risk factor for cardiovascular disease, smoking, is highly effective at controlling weight, with smokers having notably lower BMIs than non-smokers, some smokers smoking as a method of weight control and weight gain being common when quitting.  These anorexic effects have been attributed to nicotine as it effectively decreases feeding in animal models, but while nicotine has some effect on peripheral energy metabolism, little is known about its effect on central pathways determining food intake and body mass.

To investigate this the authors of this study performed a series of elegant experiments using a combination of pharmacological, molecular genetic, electrophysiological, and feeding studies in mice, to first demonstrate that specific neurons in the arcuate nucleus are acted on by nicotine and that these in turn influence pro-opiomelanocortin cells.  These constituents of the hypothalamic melanocortin system are an essential mechanism involved in the regulation of energy balance and food intake and as is demonstrated here, are influenced by nicotine to increase their firing rate and thus reduce appetite and weight gain.  Notably, naturally occurring strains of obese mice demonstrate defects in these same systems and so provide further evidence to support this mechanism as being significant in promoting weight gain.

Conclusions

These important data convincingly demonstrate the neurobiological mechanisms behind nicotine’s anorexic effects.  Further work may demonstrate new drug targets both to control smoking behaviours and to combat obesity.

• Mineur YS, Abizaid A, Rao Y, Salas R, DiLeone RJ, Gündisch D, Diano S, De Biasi M, Horvath TL, Gao XB, Picciotto MR. Nicotine decreases food intake through activation of POMC neurons. Science. 2011 Jun 10;332(6035):1330-2.