It has only been recently that the brain was identified as an insulin-sensitive organ important to regulate feeding behavior, body weight, and cognitive processes. Impaired insulin action in the brain, referred to as cerebral insulin resistance, has been linked to obesity, type 2 diabetes as well as neurodegenerative diseases.

To investigate the underlying neural mechanism of insulin action in the human brain, modern neuroimaging techniques, as functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG), have emerged as valuable tools. I will review previous studies revealing the clinical relevance of insulin signaling in the brain, by discovering that cerebral insulin resistance in obese adults is also linked to peripheral insulin resistance, age and the genetic background. Since the effects of insulin and glucose in human studies are difficult to differentiate, the intranasal administration of insulin is preferably used to investigate cerebral insulin action. This technique makes it possible to selectively deliver insulin into the brain, without relevant effects on peripheral glucose concentrations. Intervention studies have shown that intranasal insulin administration has beneficial effects on cognitive functions and weight loss, partially overcoming cerebral insulin resistance.

However, to date, specific brain areas affected by insulin resistance in humans still remain ill-defined. I will present novel fMRI data demonstrating that intranasal insulin attenuates specific brain regions of the homeostatic, reward and prefrontal circuitry in healthy normal-weight adults, potentially decreasing the rewarding properties of food. Obesity, however, dampens this attenuation, promoting an altered homeostatic set-point and potentially reduced inhibitory control contributing to overeating behavior.