Objectif This proposal aims to clarify mitochondrial contribution to obesity and thinness, using carefully characterized mitochondrial disease and obese patient materials, and genetically modified disease models. Manifestations of mitochondrial respiratory chain (RC) defects range from infantile multisystem disorders to adult-onset myopathies or neurodegeneration, and even aging-related wasting. Why defects in oxidative ATP production can lead to such variety of manifestations and tissue specificity is unknown. We have previously identified a number of gene defects that lead to RC disorders. In addition to neurological symptoms, these patients often show various metabolic manifestations: specific gene defects associate with short stature and thinness, whereas others with metabolic syndrome or obesity. This implies that specific mitochondrial defects can have opposing effects for fat storage or utilization. The involved pathways may contribute to mitochondrial disease progression, but are unknown.We propose to a) undertake a major clinical study on genetically defined, obese or thin, mitochondrial patients, and examine their metabolic phenotype in finest detail. These data will be compared to those from normal obesity, to search for common mechanisms between mitochondrial and general obesity. b) generate a set of disease models for mitochondrial disorders associated with obesity, and knock-out models for specific signallers for crossing with the disease models. c) identify in detail the involved regulatory pathways, and utilize these for searching chemical compounds that could modulate the response, and have therapeutic potential. The project has potential for major breakthroughs in the fields of mitochondrial disease pathogenesis and treatment, neurodegeneration and obesity. Champ scientifique natural sciencesbiological sciencesneurobiologymedical and health scienceshealth sciencesnutritionobesity Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Appel à propositions ERC-2010-AdG_20100317 Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil HELSINGIN YLIOPISTO Contribution de l’UE € 2 500 000,00 Adresse YLIOPISTONKATU 3 00014 Helsingin Yliopisto Finlande Voir sur la carte Région Manner-Suomi Helsinki-Uusimaa Helsinki-Uusimaa Type d’activité Higher or Secondary Education Establishments Contact administratif Berg Tiina (Ms.) Chercheur principal Anu Elina Wartiovaara (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire HELSINGIN YLIOPISTO Finlande Contribution de l’UE € 2 500 000,00 Adresse YLIOPISTONKATU 3 00014 Helsingin Yliopisto Voir sur la carte Région Manner-Suomi Helsinki-Uusimaa Helsinki-Uusimaa Type d’activité Higher or Secondary Education Establishments Contact administratif Berg Tiina (Ms.) Chercheur principal Anu Elina Wartiovaara (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
