Obiettivo Type 2 diabetes (T2D) and obesity are leading causes of mortality and are associated with the Western lifestyle, which is characterized by excessive nutritional intake and lack of exercise. A central player in the pathophysiology of these diseases is the nuclear hormone receptor (NHR) PPARγ, a lipid sensor and master regulator of adipogenesis. PPARγ is also the molecular target for the Thiazolidinedione (TZD)-class of insulin sensitizers, which command a large share of the current oral anti-diabetic drug market. Despite their efficacy in glycemic control, TZDs are associated with various adverse side effects, including weight gain, edema, and liver and cardiovascular toxicity, which limits their clinical use. During my postdoctoral research in the laboratory of dr Ronald M. Evans, at The Salk Institute, I have developed a novel screening tool for the functional analysis of complex transcriptional pathways. Using this technology, we have identified Fibroblast Growth Factor 1 (FGF1) as a novel target of PPARγ. In experiments with FGF1 knockout mice, we further demonstrated that these mice develop high-fat diet induced insulin resistance and hepatic steatosis, underscoring its significance in the development of T2DM. The studies proposed here aim to investigate the pharmacologic effects of FGF1 on energy metabolism and the development of T2D. This novel pathway defines a previously unrecognized mechanism for the insulin sensititizing actions of TZDs. Therapeutic targeting of FGF1 could serve as an improved strategy for the treatment of T2D, eliminating some of the adverse effects of TZDs that are mediated through direct activation of PPARγ. Campo scientifico medical and health sciencesbasic medicinephysiologypathophysiologymedical and health sciencesclinical medicineendocrinologydiabetesnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural sciencesmathematicspure mathematicsmathematical analysisfunctional analysismedical and health scienceshealth sciencesnutritionobesity Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Invito a presentare proposte FP7-PEOPLE-2010-RG Vedi altri progetti per questo bando Meccanismo di finanziamento MC-IRG - International Re-integration Grants (IRG) Coordinatore ACADEMISCH ZIEKENHUIS GRONINGEN Contributo UE € 100 000,00 Indirizzo HANZEPLEIN 1 9713 GZ Groningen Paesi Bassi Mostra sulla mappa Regione Noord-Nederland Groningen Overig Groningen Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Henkjan Verkade (Prof.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato