To establish the dependence of the actions of nicotine on AMPK, we investigated whether pharmacological or genetic activation of hypothalamic AMPK could reverse nicotine-induced effects on food intake and EE. First, intracerebroventricular administration of the AMPK activator AICAR reversed the hypophagia observed in rats treated with nicotine for 48 h (Fig. 6A). Second, we aimed to identify the hypothalamic nucleus where nicotine exerted its actions on AMPK. To elucidate the contribution of AMPK in the VMH to the effects of nicotine on neuropeptide expression and the thermogenesis in BAT, adenoviruses encoding either constitutively active AMPKα (AMPKα-CA) with GFP, or control virus expressing GFP alone (8,18), were injected stereotaxically into the VMH of nicotine-treated rats. Infection efficiency was assessed by 1) expression of GFP in the VMH, 2) increased hypothalamic protein concentration of pACCα, and 3) decreased hypothalamic malonyl-CoA levels (data not shown) (8,18). Overexpression of AMPKα-CA in the VMH was accompanied by increased body weight (Fig. 6B) and food intake (Fig. 6C) in nicotine-treated rats. AMPKα-CA administration also restored expression levels of AgRP, NPY, and POMC in the ARC (Fig.
