Objective 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. Fields of science 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) Topic(s) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Call for proposal ERC-2010-AdG_20100317 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Coordinator HELSINGIN YLIOPISTO Address Yliopistonkatu 3 00014 Helsingin yliopisto Finland See on map Region Manner-Suomi Helsinki-Uusimaa Helsinki-Uusimaa Activity type Higher or Secondary Education Establishments Administrative Contact Berg Tiina (Ms.) Principal investigator Anu Elina Wartiovaara (Prof.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all HELSINGIN YLIOPISTO Finland EU contribution € 2 500 000,00 Address Yliopistonkatu 3 00014 Helsingin yliopisto See on map Region Manner-Suomi Helsinki-Uusimaa Helsinki-Uusimaa Activity type Higher or Secondary Education Establishments Administrative Contact Berg Tiina (Ms.) Principal investigator Anu Elina Wartiovaara (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
