title: Nicotine enhances modulation of food-cue reactivity by leptin and ghrelin in the ventromedial prefrontal cortex.
abstract: Endocrine signals such as ghrelin and leptin are known to modulate the mesocorticolimbic dopaminergic system and, consequently, show associations with food and drug reward. In animal models, nicotine was demonstrated to reduce body weight by attenuating food intake and effects of leptin and ghrelin are partly modulated by nicotinic acetylcholine receptors which hint at potential interactions. However, the neuropharmacological modulation of endocrine signals by nicotine in healthy humans remains to be tested experimentally. We used functional magnetic resonance imaging to investigate food-cue reactivity after an overnight fast and following a caloric load (oral glucose tolerance test, OGTT) in 26 healthy normal-weight never-smokers. Moreover, we administered either nicotine (2 mg) or placebo gums using a randomized cross-over design and assessed blood plasma levels of ghrelin and leptin. During fasting, nicotine administration decreased correlations with ghrelin levels in the mesocorticolimbic system whereas correlations with leptin were increased. After the OGTT, nicotine increased the modulatory effects of ghrelin and leptin on food-cue reactivity, particularly in the ventromedial prefrontal cortex (vmPFC) and the amygdala. Critically, this led to an indirect modulation of the behavioral 'appetizer effect' (i.e. cue-induced increases in subjective appetite) by homeostatic feedback signals via food-cue reactivity in vmPFC. We conclude that nicotine enhances the effect of ghrelin and leptin in the valuation and relevance network which might, in turn, reduce appetite. This highlights that amplifying the impact of homeostatic signals such as ghrelin and leptin in normal-weight individuals might hint at a mechanism contributing to nicotine's anorexic potential.
authors: Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Germany.
authors: Nils B
authors: NB
authors: Kroemer
authors: Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Germany.
authors: Franziska
authors: F
authors: Wuttig
authors: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians Universität, Germany.
authors: Martin
authors: M
authors: Bidlingmaier
authors: Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Germany.
authors: Ulrich S
authors: US
authors: Zimmermann
authors: Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Germany.
authors: Michael N
authors: http://orcid.org/0000-0001-5398-5569
authors: MN
authors: Smolka
mesh_terms: D000328:Adult; D001066:Appetite / Q000187:drug effects*; D018592:Cross-Over Studies; D003463:Cues; D004435:Eating / Q000187:drug effects; D005215:Fasting / Q000502:physiology; D005260:Female; D005731:Ganglionic Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D054439:Ghrelin / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D020738:Leptin / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D017397:Prefrontal Cortex
chemical_list: D005731:Ganglionic Stimulants; D054439:Ghrelin; D020738:Leptin; D009538:Nicotine
keywords: Appetite; caloric intake; food; homeostatic signals; obesity; smoking