TY - JOUR A1 - Smeir, E. A1 - Leberer, S. A1 - Blumrich, A. A1 - Vogler, G. A1 - Vasiliades, A. A1 - Dresen, S. A1 - Jaeger, Carsten A1 - Gloaguen, Y. A1 - Klose, C. A1 - Beule, D. A1 - Schulze, P. A1 - Bodmer, R. A1 - Foryst-Ludwig, A. A1 - Kintscher, U. T1 - Depletion of Cardiac Cardiolipin Synthase Alters Systolic and Diastolic Function JF - iScience N2 - Cardiolipin (CL) is a major cardiac mitochondrial phospholipid maintaining regular mitochondrial morphology and function in cardiomyocytes. Cardiac CL production includes ist biosynthesis and a CL-remodeling process. Here we studied the impact of CL-biosynthesis and the enzyme Cardiolipin Synthase (CLS) on cardiac function. CLS and cardiac CL-species were significantly downregulated in cardiomyocytes following catecholamine-induced cardiac damage in mice, accompanied by increased oxygen consumption rates, signs of oxidative stress and mitochondrial uncoupling. RNAi-mediated cardiomyocyte-specific knockdown of CLS in Drosophila melanogaster resulted in marked cardiac dilatation, severe impairment of systolic performance and slower diastolic filling velocity assessed by fluorescence-based heart imaging. Finally, we showed that CL72:8 is significantly decreased in cardiac samples from patients with heart failure with reduced ejection fraction (HFrEF). In summary, we identified CLS as a regulator of cardiac function. Considering the cardiac depletion of CL-species in HFrEF, pharmacological targeting of CLS may be a promising therapeutic approach.zeige mehrzeige weniger KW - High-resolution mass spectrometry KW - Nontarget analysis KW - Heart failure KW - Cardiolipins KW - Lipidomics PY - 2021 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-536833 DO - https://doi.org/10.1016/j.isci.2021.103314 VL - 24 IS - 11 SP - 103314 PB - Cell Press AN - OPUS4-53683 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Blumrich, A. A1 - Vogler, G. A1 - Dresen, S. A1 - Diop, S. B. A1 - Jaeger, Carsten A1 - Leberer, S. A1 - Grune, J. A1 - Wirth, E. K. A1 - Hoeft, B. A1 - Renko, K. A1 - Foryst-Ludwig, A. A1 - Spranger, J. A1 - Sigrist, S. A1 - Bodmer, R. A1 - Kintscher, U. T1 - Fat-body brummer lipase determines survival and cardiac function during starvation in Drosophila melanogaster JF - iScience N2 - The cross talk between adipose tissue and the heart has an increasing importance for cardiac function under physiological and pathological conditions. This study characterizes the role of fat body lipolysis for cardiac function in Drosophila melanogaster. Perturbation of the function of the key lipolytic enzyme, brummer (bmm), an ortholog of themammalian ATGL (adipose triglyceride lipase) exclusively in the fly’s fat body, protected the heart against starvation-induced dysfunction. We further provide evidence that this protection is caused by the preservation of glycerolipid stores, resulting in a starvation-resistant maintenance of energy supply and adequate cardiac ATP synthesis. Finally, we suggest that alterations of lipolysis are tightly coupled to lipogenic processes, participating in the preservation of Lipid energy substrates during starvation. Thus, we identified the inhibition of adipose tissue lipolysis and subsequent energy preservation as a protective mechanism against cardiac dysfunction during catabolic stress. KW - High-resolution mass spectrometry KW - Nontarget analysis PY - 2021 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-528756 DO - https://doi.org/10.1016/j.isci.2021.102288 VL - 24 IS - 4 SP - 102288 AN - OPUS4-52875 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -