Main
obesity, metabolic dysfunction, metabolic impairments, associative learning
OBESITY, INSULIN RESISTANCE, INSULIN SENSITIVITY
Learning associations emerging from the sensory information that we perceive in a changing environment are essential to survive and thrive under selective pressureThe regulation of energy balance, for instance, requires our behaviour to adapt to our physiological needsOn a neural level, dopamine (DA) neurons of the ventral midbrain and their projection targets promote adaptive behaviour by regulating motivation and reinforcing actions through DA-dependent plasticityFurthermore, the amplitude of an error needs to be put in perspective with the precision of the relative predictionIn the more general context of associative learning, and in addition to the above, prediction errors indicate a need to update current beliefs about incoming sensory inputsSimilarly, insulin action on these neurons depresses excitatory synaptic transmissionIn line with this hypothesis, the overconsumption of food and, ultimately, obesity relate to metabolic impairments reflected by reduced insulin sensitivityIntriguingly, recent evidence suggests that GLP-1 receptor agonists augment glucose-dependent insulin releaseTherefore, we performed a randomized, placebo-controlled crossover functional magnetic resonance imaging (fMRI) study to assess the effect of GLP-1 receptor activation on associative learning in humans with and without metabolic dysfunction. We recruited as participants lean individuals and those with obesity and assessed their peripheral insulin sensitivity using the homeostasis model assessment of insulin resistance (HOMA-IR)