Objective This MSCA Reintegration proposal is aimed to study the heterogeneity of neuronal populations implicated in the maintenance of energy balance. Because of their location, neurons in the arcuate nucleus of the hypothalamus (ARC) integrate nutrient and hormonal signals carried in the blood. Then, they regulate downstream neuron’s activity in order to adapt food intake and energy expenditure. Deregulation of energy homeostasis can lead to obesity and diabetes, two of the major chronic diseases in the EU. AgRP neurons, an ARC population, have a prominent role in the regulation of food intake and systemic insulin sensitivity. They establish axonal projections with several brain areas and recent evidences show that each sub-circuit can have a specific function in the regulation of food intake and/or glucose homeostasis. For this fellowship I propose to use an innovative experimental approach to investigate a specific novel AgRP neuronal subpopulation, characterized by the expression of the UDP-receptor, P2Y6, as a first step to unravel the heterogeneity of the total population. Although P2Y6 activation increases short-term food intake, its effects on glucose homeostasis are still unknown. I plan to combine new recombinase technologies with state of the art techniques to genetically identify the AgRP, P2Y6 subpopulation and then: 1) characterize their in vivo dynamic response to physiological activators; 2) map specific AgRP+, P2Y6+ sub-circuits and dissect their role in each facet of energy homeostasis; and 3) investigate new molecular markers, as possible drugable targets. Results from this project will unveil new aspects of neuronal heterogeneity that participate in the regulation of energy homeostasis and will contribute to design new strategies to curb the actual obesity trends. The completion of this MSCA fellowship represents an exceptional opportunity to reinforce my professional maturity and to develop my independent research line. Fields of science medical and health scienceshealth sciencespublic healthmedical and health sciencesclinical medicineendocrinologydiabetesmedical and health sciencesclinical medicinecardiologycardiovascular diseasesmedical and health sciencesbasic medicinephysiologyhomeostasismedical and health scienceshealth sciencesnutritionobesity Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2016 - Individual Fellowships Call for proposal H2020-MSCA-IF-2016 See other projects for this call Funding Scheme MSCA-IF-EF-RI - RI – Reintegration panel Coordinator MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Net EU contribution € 171 460,80 Address HOFGARTENSTRASSE 8 80539 Munchen Germany See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 171 460,80