Astrocyte-neuron COmmunication in METabolism and obesity.

ended

Obesity and type 2 diabetes have been increasing during the last decades, becoming highly prevalent diseases in our society. Until very recently, astrocytes and other glial cells have been traditionally known as supportive cells to neurons, but the host research group led by Prof. Matthias Tschöp has recently reported that insulin receptors (IRs) in astrocytes regulate glucose delivery into the brain and lack thereof leads to a reduced response of glucose-induced suppression of food intake (Garcia-Caceres et al., Cell 2016). These data, together with previous findings, suggest a new paradigm in which astrocytes interplay with neurons in the CNS control of metabolism, body weight, and energy balance. However, the molecular underpinnings remain to be investigated. My main objective is to test the hypothesis that astrocyte-neuron communication is required for maintaining a normal energy homeostasis, and its impairment contributes to the pathogenesis of obesity. To achieve this, I will use Designer Receptors Exclusively Activated by Designer Drugs (DREADD) technology to examine whether astrocyte activity is required for maintaining a normal energy homeostasis. I will generate two transgenic mouse models (dnSNARE mouse and iBot mouse) to specifically interfere with the release of gliotransmitters in order to test whether astrocytes release vesicles to regulate the activity of hypothalamic neurons in the control of energy metabolism. Finally, I will investigate whether hypercaloric diet disrupts astrocyte-neuron communication, thus contributing to obesity progression. This project has the potential to reveal new mechanism(s) of metabolic homeostasis and how its impairment explains the development of obesity. Moreover, this proposal will enhance my individual competence in terms of skill acquisition and creativity through an advanced training in a privileged host environment; representing all together a significant contribution to the Horizon 2020 Work Programme.