Our focus in the neurobiology of insulin peptides (ILPs) as a model system in the body→brain dialog provides us with a specific paradigm to approach the intricate physiological network relating metabolism and brain health. Building on previous work that led to positioning ILPs as relevant components of brain homeostasis and consequently, of neurodegenerative diseases, we are currently working on two aspects of ILP neurobiology. A first one relates to the role played by these hormones in brain metabolism, focusing most prominently on astrocytes and their support to neurons. A second one is aimed to define specific circuits underlying the pleiotropy of ILPs, such as the orexin system in the lateral hypothalamus. From a more general perspective we are using a multidisciplinary approach “from molecules to behavior” to determine mechanisms whereby life-style factors (physical exercise, stress, diet, social engagement…etc) modulate the activity of the Insulin/ IGF-I dyad in the brain and its physiological and pathological impacts.