Central insulin modulates food valuation via mesolimbic pathways

Central insulin is thought to act at the neural interface between metabolic and hedonic drives to eat. Here, using pharmacological fMRI, we show that intranasal insulin (INI) changes the value of food cues through modulation of mesolimbic pathways. Overnight fasted participants rated the palatability of food pictures and attractiveness of non-food items (control) after receiving INI or placebo. We report that INI reduces ratings of food palatability and value signals in mesolimbic regions in individuals with normal insulin sensitivity. Connectivity analyses reveal insulinergic inhibition of forward projections from the ventral tegmentum to the nucleus accumbens. Importantly, the strength of this modulation predicts decrease of palatability ratings, directly linking neural findings to behaviour. In insulin-resistant participants however, we observe reduced food values and aberrant central insulin action. These data demonstrate how central insulin modulates the cross-talk between homeostatic and non-homeostatic feeding systems, suggesting that dysfunctions of these neural interactions may promote metabolic disorders. The influence of insulin on food preference and the corresponding underlying neural circuits are unknown in humans. Here, the authors show that increasing insulin changes food preference by modulating mesolimbic neural circuits, and that this pattern is changed in insulin-resistant individuals.