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    Adipose tissue ATGL modifies the cardiac lipidome in pressure-overload-induced left ventricular failure (2018)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Salatzki, Janek
    Foryst-Ludwig, Anna
    Bentele, Kajetan
    Blumrich, Annelie
    Smeir, Elia
    Ban, Zsofia
    Brix, Sarah
    Grune, Jana
    Beyhoff, Niklas
    Klopfleisch, Robert (WE 12)
    Dunst, Sebastian
    Surma, Michal A
    Klose, Christian
    Rothe, Michael
    Heinzel, Frank R
    Krannich, Alexander
    Kershaw, Erin E
    Beule, Dieter
    Schulze, P Christian
    Marx, Nikolaus
    Kintscher, Ulrich
    Quelle
    PLoS Genetics
    Bandzählung: 14
    Heftzählung: 1
    Seiten: e1007171
    ISSN: 1553-7390
    Sprache
    Englisch
    Verweise
    DOI: 10.1371/journal.pgen.1007171
    Pubmed: 29320510
    Kontakt
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    14163 Berlin
    +49 30 838 62450
    pathologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Adipose tissue lipolysis occurs during the development of heart failure as a consequence of chronic adrenergic stimulation. However, the impact of enhanced adipose triacylglycerol hydrolysis mediated by adipose triglyceride lipase (ATGL) on cardiac function is unclear. To investigate the role of adipose tissue lipolysis during heart failure, we generated mice with tissue-specific deletion of ATGL (atATGL-KO). atATGL-KO mice were subjected to transverse aortic constriction (TAC) to induce pressure-mediated cardiac failure. The cardiac mouse lipidome and the human plasma lipidome from healthy controls (n = 10) and patients with systolic heart failure (HFrEF, n = 13) were analyzed by MS-based shotgun lipidomics. TAC-induced increases in left ventricular mass (LVM) and diastolic LV inner diameter were significantly attenuated in atATGL-KO mice compared to wild type (wt) -mice. More importantly, atATGL-KO mice were protected against TAC-induced systolic LV failure. Perturbation of lipolysis in the adipose tissue of atATGL-KO mice resulted in the prevention of the major cardiac lipidome changes observed after TAC in wt-mice. Profound changes occurred in the lipid class of phosphatidylethanolamines (PE) in which multiple PE-species were markedly induced in failing wt-hearts, which was attenuated in atATGL-KO hearts. Moreover, selected heart failure-induced PE species in mouse hearts were also induced in plasma samples from patients with chronic heart failure. TAC-induced cardiac PE induction resulted in decreased PC/ PE-species ratios associated with increased apoptotic marker expression in failing wt-hearts, a process absent in atATGL-KO hearts. Perturbation of adipose tissue lipolysis by ATGL-deficiency ameliorated pressure-induced heart failure and the potentially deleterious cardiac lipidome changes that accompany this pathological process, namely the induction of specific PE species. Non-cardiac ATGL-mediated modulation of the cardiac lipidome may play an important role in the pathogenesis of chronic heart failure.