Objectif The major interest of my research activity is to understand the pathophysiological mechanisms leading to the development of obesity, particularly focusing on the role of the central nervous system (CNS) in this context. The CNS is the critical organ for the coordination of intracellular metabolic processes that are essential to guarantee energy homeostasis at the organism level. Thus, centering my studies on the atypical kinase mammalian Target Of Rapamycin (mTOR), I recently demonstrated that this evolutionarily conserved fuel sensing pathway integrates sensory inputs from nutrients and hormones within the hypothalamus, in order to modulate food intake and body weight. The ciliary neurotrophic factor (CNTF) is a cytokine whose central administration reduces body weight even in leptin-resistant states, including diet-induced obesity, and causes a weight loss that is maintained after therapy discontinuation. The explanation for this long-term effect of CNTF on energy balance likely resides in its newly described ability to induce neurogenesis within the adult murine hypothalamus. Cellular development and differentiation are tightly coordinated with nutritional status; and induction of mitogenic signaling and neuronal differentiation is known to involve modulation of the mTOR signaling. Thus, I propose that the CNTF effects on neurogenesis and energy balance require the activation of the hypothalamic mTOR signaling pathway. To investigate this hypothesis, I will use a multidisciplinary approach, including the use of genetically modified mice, specific behavioral paradigms and molecular strategies. These studies will clarify the role of cellular fuel sensing mechanisms in the regulation of energy balance and possibly highlight the function of processes, such as neurogenesis and neuronal differentiation, which might be important for the appropriate regulation of energy balance within the hypothalamus and that might require a functional mTOR signaling cascade. Champ scientifique natural sciencesbiological sciencesneurobiologyengineering and technologyenvironmental engineeringenergy and fuelsmedical and health sciencesbasic medicinephysiologyhomeostasismedical and health scienceshealth sciencesnutritionobesity Mots‑clés Brain research Neurobiology Physiology energy balance feeding behavior neurogenesis target of rapamycin Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) PEOPLE-2007-4-3.IRG - Marie Curie Action: "International Reintegration Grants" Appel à propositions FP7-PEOPLE-2007-4-3-IRG Voir d’autres projets de cet appel Régime de financement MC-IRG - International Re-integration Grants (IRG) Coordinateur INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Contribution de l’UE € 50 000,00 Adresse RUE DE TOLBIAC 101 75654 Paris France Voir sur la carte Région Ile-de-France Ile-de-France Paris Type d’activité Research Organisations Contact administratif Pier-Vincenzo Piazza (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée