Projektbeschreibung
Neue Ära der Entwicklung von Medikamenten gegen Adipositas
Adipositas, eine eskalierende Krise der öffentlichen Gesundheit, geht mit einem alarmierenden Anstieg chronischer Krankheiten wie Diabetes, Herz-Kreislauf-Erkrankungen und Krebs einher. Die komplizierte Steuerung des Energiehaushalts, die vom Nucleus arcuatus des Hypothalamus gelenkt wird, nimmt dabei eine zentrale Rolle ein. Doch ungeachtet unseres Wissens über diese zentrale Regulierung sind uns bisher wirksame Behandlungen verwehrt geblieben. Das Ziel des im Rahmen der Marie-Skłodowska-Curie-Maßnahmen unterstützten Projekts FEEDING besteht darin, diese Komplexität besser zu verstehen, indem sich das Team in das unerforschte Gebiet der verwaisten G-Protein-gekoppelten Rezeptoren und deren Interaktion mit Leptinrezeptoren vorwagt. Die Forschenden versuchen, mithilfe des ausgeklügelten Einsatzes von Knockout-Modellen, pharmakologischen Wirkstoffen und Stoffwechseluntersuchungen den Code der Leptinresistenz zu knacken. Dieses Unterfangen birgt das Potenzial, den Kampf gegen Adipositas neu zu definieren.
Ziel
"Obesity is a major burden to public health as it increases the risk of several chronic diseases, like diabetes, cardiovascular diseases, musculoskeletal disorders or some cancers. Energy homeostasis is centrally regulated by the hypothalamus where the arcuate nucleus (ARC) orchestrates feeding behaviors and energy balance. Two neuronal populations of the ARC are considered as the first-order neurons mediating the effects of various signals such as leptin and insulin, the orexigenic neuropeptide (NP)Y/Agouti-related peptide (AgRP) neurons and the anorexigenic pro-opiomelanocortin (POMC)/Amphetamine-regulated transcript (CART) neurons. Leptin is an adipocyte-secreted peptidic hormone that inhibits food intake and regulates body weight. Nearly in all forms of obesity, circulating levels of leptin increase but fail to suppress food intake and body weight. This condition has been identified as ""leptin resistance"".
G protein-coupled receptors (GPCRs) are the largest family of membrane proteins and a notoriously successful source of drug targets. However, many GPCRs are understudied or even orphans meaning they have no known ligands. Despite our knowledge of the principal circuits regulating feeding, satiety, hunger and energy expenditure, we have been unable to deliver effective drugs targeting these systems. The failure in targeting the melanocortin pathways comes out partly from an incomplete understanding of leptin action, especially leptin resistance, at the central level. Here, we propose to investigate the interplay between the signaling of orphan GPCR and leptin receptor in leptin sensitive cells of the arcuate nucleus. To do so, we will use conditional knockout animals and pharmacological modulators. We will measure various metabolic parameters including weight and food intake with the Comprehensive Laboratory Animal Monitoring System (CLAMS). We will also establish hypothalamic cell cultures in which we will address the impact of G protein signaling on leptin."
Wissenschaftliches Gebiet
- medical and health scienceshealth sciencespublic health
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicinecardiologycardiovascular diseases
- medical and health sciencesbasic medicinephysiologyhomeostasis
- medical and health scienceshealth sciencesnutritionobesity
Schlüsselbegriffe
Programm/Programme
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Aufforderung zur Vorschlagseinreichung
Andere Projekte für diesen Aufruf anzeigenFinanzierungsplan
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsKoordinator
4000 Liege
Belgien