Our data support the pathophysiological relevance of the hypothalamic AMPK-BAT axis in the control of energy balance (7,8,41) and demonstrate that the well-established effects of nicotine on body weight are mediated through this mechanism. These results also raise the question of its suitability as a therapeutic target for the treatment of human obesity. Up to now this was considered unlikely because of the well-known addictive actions of nicotine. Our data, however, show that its effects on increasing EE are mediated by a specific hypothalamic nuclei, the VMH (8). VMH neurons play a minor role in the rewarding properties of nicotine (31), indicating that by targeting this nicotine-activated pathway it may be feasible to preserve nicotine's effect on body weight without developing addiction. Further work addressing this issue is clearly merited, since it has also been demonstrated that peripheral AMPK is a suitable target for human disease using, for example, metformin and thiazolidinediones to improve insulin sensitivity (14,15). Current evidence has highlighted the importance of BAT in adult humans and its potential as an alternative to the existing strategies to solely
