title: Adipose Tissue Lipolysis Promotes Exercise-induced Cardiac Hypertrophy Involving the Lipokine C16:1n7-Palmitoleate.
abstract: Endurance exercise training induces substantial adaptive cardiac modifications such as left ventricular hypertrophy (LVH). Simultaneously to the development of LVH, adipose tissue (AT) lipolysis becomes elevated upon endurance training to cope with enhanced energy demands. In this study, we investigated the impact of adipose tissue lipolysis on the development of exercise-induced cardiac hypertrophy. Mice deficient for adipose triglyceride lipase (Atgl) in AT (atATGL-KO) were challenged with chronic treadmill running. Exercise-induced AT lipolytic activity was significantly reduced in atATGL-KO mice accompanied by the absence of a plasma fatty acid (FA) increase. These processes were directly associated with a prominent attenuation of myocardial FA uptake in atATGL-KO and a significant reduction of the cardiac hypertrophic response to exercise. FA serum profiling revealed palmitoleic acid (C16:1n7) as a new molecular co-mediator of exercise-induced cardiac hypertrophy by inducing nonproliferative cardiomyocyte growth. In parallel, serum FA analysis and echocardiography were performed in 25 endurance athletes. In consonance, the serum C16:1n7 palmitoleate level exhibited a significantly positive correlation with diastolic interventricular septum thickness in those athletes. No correlation existed between linoleic acid (18:2n6) and diastolic interventricular septum thickness. Collectively, our data provide the first evidence that adipose tissue lipolysis directly promotes the development of exercise-induced cardiac hypertrophy involving the lipokine C16:1n7 palmitoleate as a molecular co-mediator. The identification of a lipokine involved in physiological cardiac growth may help to develop future lipid-based therapies for pathological LVH or heart failure.
authors.affiliation: From the Institute of Pharmacology, Center for Cardiovascular Research, Charité-Universitaetsmedizin Berlin, 10115 Berlin, Germany, the DZHK (German Center for Cardiovascular Research), 10115 Berlin, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Foryst-Ludwig
authors.affiliation: the Department of Nuclear Medicine, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Kreissl
authors.affiliation: From the Institute of Pharmacology, Center for Cardiovascular Research, Charité-Universitaetsmedizin Berlin, 10115 Berlin, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Benz
authors.affiliation: From the Institute of Pharmacology, Center for Cardiovascular Research, Charité-Universitaetsmedizin Berlin, 10115 Berlin, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Brix
authors.affiliation: From the Institute of Pharmacology, Center for Cardiovascular Research, Charité-Universitaetsmedizin Berlin, 10115 Berlin, Germany.
authors.forename: Elia
authors.initials: E
authors.lastname: Smeir
authors.affiliation: From the Institute of Pharmacology, Center for Cardiovascular Research, Charité-Universitaetsmedizin Berlin, 10115 Berlin, Germany.
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Ban
authors.affiliation: From the Institute of Pharmacology, Center for Cardiovascular Research, Charité-Universitaetsmedizin Berlin, 10115 Berlin, Germany.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Januszewicz
authors.affiliation: From the Institute of Pharmacology, Center for Cardiovascular Research, Charité-Universitaetsmedizin Berlin, 10115 Berlin, Germany.
authors.forename: Janek
authors.initials: J
authors.lastname: Salatzki
authors.affiliation: From the Institute of Pharmacology, Center for Cardiovascular Research, Charité-Universitaetsmedizin Berlin, 10115 Berlin, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Grune
authors.affiliation: From the Institute of Pharmacology, Center for Cardiovascular Research, Charité-Universitaetsmedizin Berlin, 10115 Berlin, Germany.
authors.forename: Anne-Kathrin
authors.initials: AK
authors.lastname: Schwanstecher
authors.affiliation: From the Institute of Pharmacology, Center for Cardiovascular Research, Charité-Universitaetsmedizin Berlin, 10115 Berlin, Germany.
authors.forename: Annelie
authors.initials: A
authors.lastname: Blumrich
authors.affiliation: the Department of Nuclear Medicine, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schirbel
authors.affiliation: the Department of Veterinary Pathology, College of Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Klopfleisch
authors.affiliation: the Lipidomix GmbH, 13088 Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Rothe
authors.affiliation: the Department of Prevention, Rehabilitation, and Sports Medicine, Technische Universitaet Muenchen, 80809 Muenchen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Blume
authors.affiliation: the Department of Prevention, Rehabilitation, and Sports Medicine, Technische Universitaet Muenchen, 80809 Muenchen, Germany, the DZHK (German Center for Cardiovascular Research), Munich Heart Alliance, 80809 Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Halle
authors.affiliation: the Department of Sports Medicine, Humboldt University/Charité-Universitaetsmedizin Berlin, 10115 Berlin, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Wolfarth
authors.affiliation: the Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, and.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Kershaw
authors.affiliation: From the Institute of Pharmacology, Center for Cardiovascular Research, Charité-Universitaetsmedizin Berlin, 10115 Berlin, Germany, the DZHK (German Center for Cardiovascular Research), 10115 Berlin, Germany ulrich.kintscher@charite.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kintscher
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology* / Q000378:metabolism; D002460:Cell Line; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism*; D008066:Lipolysis; D051379:Mice; D018345:Mice, Knockout; D010805:Physical Conditioning, Animal
chemical_list: D005229:Fatty Acids, Monounsaturated; C008757:palmitoleic acid
keywords: adipose tissue metabolism; adipose triglyceride lipase (ATGL); cardiac hypertrophy; cardiac metabolism; lipid signaling