nicotinic acetylcholine receptors, which have recently been demonstrated to be involved in the action of nicotine in the hypothalamus (3). Together, these results suggest the existence of a mechanistic link between hypothalamic AMPK function and nicotine-induced changes in energy homeostasis. To specifically address this hypothesis we investigated whether activation of hypothalamic AMPK could prevent the anorexigenic and thermogenic effects of nicotine. We first showed that intracerebroventricular administration of the AMPK activator AICAR reversed nicotine-induced anorexia. Secondly, overexpression of AMPKα-CA in the VMH reversed the anorectic and thermogenic effects observed in nicotine-treated rats. The VMH is considered as a key hypothalamic nucleus controlling both sides of the energy balance equation (feeding and EE) (41–43), and recent evidence has demonstrated that AMPK in this nucleus plays a major role in its ability to do so (8,18,41). In addition, our data demonstrate that genetic overactivation of AMPK in the VMH totally reversed the nicotine-induced anorexia and weight loss. AMPK-mediated normalization of energy balance was associated with normalized mRNA levels of AgRP, NPY, and POMC in the ARC, as well as reduced or restored levels of thermogenic markers in BAT increased previously by nicotine treatment. Overall, our results indicate that nicotine impairs AMPK function
