Abstract 15489: Adipose Tissue Lipolysis Modifies the Cardiac Lipidome in Chronic Heart Failure
Introduction: Adipose tissue lipolysis often occurs during the development of heart failure as a consequence of chronic adrenergic stimulation and increased natriuretic peptide levels. However, the impact of enhanced adipose triacylglycerol hydrolysis on cardiac function is mainly unknown.
Hypothesis: Adipose tissue lipolysis regulates cardiac function and the cardiac lipidome.
Methods: To investigate the role of fat tissue lipolysis during heart failure development we generated mice with impaired lipolytic capacity. Mice deficient for adipose triglyceride lipase (ATGL) (atATGL-KO) were subjected to transverse aortic constriction (TAC) and phenotyped after 11 weeks. The cardiac mouse lipidome was analyzed by shotgun lipidomics using a Q Exactive mass spectrometer in quadrupole-Orbitrap configuration. The profiling encompassed 542 lipid species from 16 different classes.
Results: We have recently shown that TAC-induced cardiac dysfunction was attenuated in atATGL-KO compared to wild-type (wt) mice. In particular, pressure-induced increases in left ventricular mass (LVM) and diastolic LV inner diameter were significantly reduced in atATGL-KO mice. In addition, atATGL-KO mice were completely protected against TAC-induced systolic LV-failure. Perturbation of lipolysis in adipose tissue in atATGL-KO mice resulted in the prevention of major cardiac lipidome changes observed after TAC in wt mice. Major changes occurred in the lipid class of phosphatidylethanolamines (PE) in which multiple PE-species (PE18:0-20:4; PE16:0-18:1; PE16:0-18:2; PE16:0-20:4; PE17:0-20:4; PE18:0-22:4; PE18:1-18:1; PE18:2-18:0; PE18:2-19:0) were markedly induced in failing wt-hearts. This was attenuated in atATGL-KO hearts. TAC-induced cardiac PE induction resulted in a lipid species-specific decrease of PC/ PE-ratios almost exclusively in failing wt-hearts, a process previously associated with enhanced apoptosis.
Conclusions: Perturbation of adipose tissue lipolysis leads to an improvement of pressure-induced heart failure accompanied with the prevention of deleterious cardiac lipidome changes. Non-cardiac mediated-modulation of the cardiac lipidome may play an important role in the pathogenesis of chronic heart failure.
Author Disclosures: A. Blumrich: None. J. Salatzki: None. A. Foryst-Ludwig: None. K. Bentele: None. E. Smeir: None. Z. Ban: None. S. Brix: None. J. Grune: None. R. Klopfleisch: None. C. Klose: Employment; Significant; Employee of Lipotype GmbH. E.E. Kershaw: None. D. Beule: None. N. Marx: None. U. Kintscher: None.
- © 2016 by American Heart Association, Inc.