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Arrhythmia causes lipid accumulation and reduced glucose uptake

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An Invited Editorial to this article was published on 28 May 2015

Abstract

Atrial fibrillation (AF) is characterized by irregular contractions of atrial cardiomyocytes and increased energy demand. The aim of this study was to characterize the influence of arrhythmia on glucose and fatty acid (FA) metabolism in cardiomyocytes, mice and human left atrial myocardium. Compared to regular pacing, irregular (pseudo-random variation at the same number of contractions/min) pacing of neonatal rat cardiomyocytes induced shorter action potential durations and effective refractory periods and increased diastolic [Ca2+]c. This was associated with the activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and AMP-activated protein kinase (AMPK). Membrane expression of fatty acid translocase (FAT/CD36) and 14C-palmitic acid uptake were augmented while membrane expression of glucose transporter subtype 4 (GLUT-4) as well as 3H-glucose uptake were reduced. Inhibition of AMPK and CaMKII prevented these arrhythmia-induced metabolic changes. Similar alterations of FA metabolism were observed in a transgenic mouse model (RacET) for spontaneous AF. Consistent with these findings samples of left atrial myocardium of patients with AF compared to matched samples of patients with sinus rhythm showed up-regulation of CaMKII and AMPK and increased membrane expression of FAT/CD36, resulting in lipid accumulation. These changes of FA metabolism were accompanied by decreased membrane expression of GLUT-4, increased glycogen content and increased expression of the pro-apoptotic protein bax. Irregular pacing of cardiomyocytes increases diastolic [Ca2+]c and activation of CaMKII and AMPK resulting in lipid accumulation, reduced glucose uptake and increased glycogen synthesis. These metabolic changes are accompanied by an activation of pro-apoptotic signalling pathways.

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Acknowledgments

We thank Ellen Becker, Simone Jäger and Catrin Pittke for their excellent technical assistance. This study was funded by grants of the Deutsche Forschungsgemeinschaft (DFG) to UL, OA, CM, MB), the Deutsche Gesellschaft für Kardiologie (DGK) to ML, the HOMFOR Programm to ML, OA, and the Universität des Saarlandes to ML, OA.

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Authors and Affiliations

  1. Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, 66421, Homburg, Germany

    Matthias Lenski, Gregor Schleider, Michael Kohlhaas, Lucas Adrian, Oliver Adam, Christoph Maack, Michael Böhm & Ulrich Laufs

  2. Institut für Molekulare Zellbiologie, Universität des Saarlandes, 66421, Homburg, Germany

    Qinghai Tian, Lars Kaestner & Peter Lipp

  3. Medizinische Klinik I, Klinik für Kardiologie, Pneumologie, Angiologie und Internistische Intensivmedizin, Uniklinik RWTH Aachen, 52074, Aachen, Germany

    Michael Lehrke

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  1. Matthias Lenski
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Correspondence to Matthias Lenski.

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To this original contribution an invited editorial is available at doi:10.1007/s00395-015-0498-1.

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Lenski, M., Schleider, G., Kohlhaas, M. et al. Arrhythmia causes lipid accumulation and reduced glucose uptake. Basic Res Cardiol 110, 40 (2015). https://doi.org/10.1007/s00395-015-0497-2

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