Sex differences in adipose tissue lipolysis and pathological cardiac hypertrophy
Final Report Abstract
Our previous study indicates that adipose tissue ATGL is an important regulator of exercise-induced lipolysis and modulates circulating FA levels during physical training. Importantly, training induced cardiac FA- and glucose uptake is also determined by ATGL-mediated FA-mobilization from adipose tissue. In addition to cardiac metabolism, adipose ATGL seems to control the development of cardiac hypertrophy during exercise. We were able to demonstrate, that palmitoleic acid (C16:1), released from adipose tissue in an ATGL-dependent manner, serves as a molecular mediator of exercise- induced cardiac hypertrophy in vivo and in vitro. The molecular mechanism by which C16:1 is able to induce a hypertrophic response in cardiomyocytes reminds elusive. A planned next-generation RNA sequencing study would allowed the identification of new target genes/transcripts regulated during C16:1-mediated hypertrophic response in both human and murine primary cardiomyocytes. Taken together, these data suggest that lipid species imply the potential as new molecular markers and therapeutic agents for cardiovascular disease.
Publications
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Metabolic impact of estrogen signalling through ERalpha and ERbeta. J Steroid Biochem Mol Biol. 2010 Oct;122(1-3):74-81
Foryst-Ludwig A, Kintscher U
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Sex differences in physiological cardiac hypertrophy are associated with exercise-mediated changes in energy substrate availability. Am J Physiol Heart Circ Physiol. 2011;301:H115-122
Foryst-Ludwig A, Kreissl MC, Sprang C, Thalke B, Bohm C, Benz V, Gurgen D, Dragun D, Schubert C, Mai K, Stawowy P, Spranger J, Regitz-Zagrosek V, Unger T, Kintscher U
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High-mobility group A1 protein: a new coregulator of peroxisome proliferator-activated receptor-gamma-mediated transrepression in the vasculature. Circ Res. 2012 Feb 3;110(3):394-405
Bloch M, Prock A, Paonessa F, Benz V, Bahr IN, Herbst L, et al.
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Sex-specific differences in Type 2 Diabetes Mellitus and dyslipidemia therapy: PPAR agonists. Handb Exp Pharmacol. 2012(214):387-410
Benz V, Kintscher U, Foryst-Ludwig A
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Sex differences in exercise-induced cardiac hypertrophy. Pflugers Arch. 2013 May;465(5):731-7
Foryst-Ludwig A, Kintscher U
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Sexual dimorphism in obesity- mediated left ventricular hypertrophy. Am J Physiol Heart Circ Physiol. 2013 Jul;305(2):H211-8
Bohm C, Benz V, Clemenz M, Sprang C, Hoft B, Kintscher U, et al.
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Adipose Tissue Lipolysis Promotes Exerciseinduced Cardiac Hypertrophy Involving the Lipokine C16:1n7-Palmitoleate. J Biol Chem. 2015;290:23603-23615
Foryst-Ludwig A, Kreissl MC, Benz V, Brix S, Smeir E, Ban Z, Januszewicz E, Salatzki J, Grune J, Schwanstecher AK, Blumrich A, Schirbel A, Klopfleisch R, Rothe M, Blume K, Halle M, Wolfarth B, Kershaw EE, Kintscher U
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Gender in cardiovascular diseases: impact on clinical manifestations, management, and outcomes. Eur Heart J. 2016;37:24-34
Regitz-Zagrosek V, Oertelt-Prigione S, Prescott E, Franconi F, Gerdts E, Foryst-Ludwig A, Maas AH, Kautzky-Willer A, Knappe-Wegner D, Kintscher U, Ladwig KH, Schenck- Gustafsson K, Stangl V
