Lipid-mediated mitochondrial dysfunction in HFpEF during obesity (A09)

• Subject Area: Pharmacology ; General Genetics and Functional Genome Biology ; Cardiology, Angiology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437531118

Obesity and ageing is a main pathogenic driver of HFpEF and accompanied by pronounced disturbances of lipid metabolism which, to a large extent, are based on adipose tissue (AT) dysfunction. In parallel, obesity results in cardiac mitochondrial dysfunction during HFpEF. It is currently unknown whether this mitochondrial dysfunction results from an intrinsic cardiac damage or whether it is, more likely, a cardiac response to systemic, non-cardiac dysfunction finally inducing HFpEF. Thus, the main research question of this project has been defined as follows: Does AT-lipid metabolism control cardiac and mitochondrial function in HFpEF, in particular in obese phenotypes? To answer this question, we will manipulate lipid uptake in AT-specific knockout mouse models which will be challenged with HFpEF. To delineate critical cardiac pathways relevant for AT-controlled cardiac function, the mouse model will be complemented by a Drosophila model (lean/obese) of heart failure with diastolic dysfunction and impaired lipid uptake in the fly fat body.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1470: Multilevel mechanistic characterisation of Heart Failure with Preserved Ejection Fraction - Towards a novel classification of HFpEF for targeted therapies
• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Project Heads: Professor Dr. Ulrich Kintscher; Professor Dr. Stephan J. Sigrist