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AMPK Prevents Palmitic Acid-Induced Apoptosis and Lipid Accumulation in Cardiomyocytes

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Lipids

Abstract

Palmitic acid, a main fatty acid (FA) in human nutrition, can induce apoptosis of cardiomyocytes. However, a specific combination of palmitic, myristic and palmitoleic acid (CoFA) has been reported to promote beneficial cardiac growth. The aim of this study was to investigate the relevance of CoFA for cardiac growth and to delineate the underlying signaling pathways of CoFA and palmitic acid treatment. CoFA treatment of C57Bl/6 mice increased FA serum concentrations. However, morphologic and echocardiographic analysis did not show myocardial hypertrophy. Cell culture studies using rat ventricular cardiomyocytes revealed an increased phosphorylation of AMP activated protein kinase α (AMPKα) to 155 ± 19% and its target acetyl-CoA-carboxylase to 177 ± 23% by CoFA. Treatment with myristic acid also increased AMPKα phosphorylation to 189 ± 32%. Palmitic acid did not activate AMPKα but increased expression of the FA translocase CD36 (FAT/CD36) to 163 ± 23% and adipose-differentiation-related-protein (ADRP), a sensitive marker of lipid accumulation, to 168 ± 42%. This was associated with an increased phosphorylation of the stress-activated-protein-kinase/Jun-amino-terminal-kinase (SAPK/JNK) to 173 ± 27%. In CoFA-treated cells, phosphorylation of SAPK/JNK was unaltered. FACS analysis revealed increased apoptosis to 159 ± 5% by palmitic acid but not by CoFA. AMPK activator AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) prevented up-regulation of ADRP and increased apoptosis by palmitic acid. Confirming these findings, inhibition of AMPK by compound C in CoFA-treated cardiomyocytes resulted in an increased expression of ADRP to 154 ± 27%, FAT/CD36 to 167 ± 28% and apoptosis to 183 ± 12%. These data reveal that AMPK activation plays an important role in prevention of palmitic acid-induced apoptosis and lipid accumulation in cardiomyocytes.

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Abbreviations

CoFA:

Combination of the FA palmitic, myristic and palmitoleic acid

FA:

Fatty acid

AMPK:

AMP activated protein kinase

ACC:

Acetyl-CoA-carboxylase

FAT/CD36:

Fatty acid translocase CD36

ADRP:

Adipose differentiation related protein

SAPK/JNK:

Stress-activated protein kinase/Jun-amino-terminal kinase

AICAR:

5-Aminoimidazole-4-carboxamide ribonucleotide

GLUT-4:

Glucose transporter 4

BSA:

Bovine serum albumin

TAC:

Transaortic constriction

PPAR:

Peroxisome proliferator-activated receptor

ROS:

Reactive oxygen species

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Acknowledgements

We thank Ellen Becker and Simone Jäger for an excellent technical assistance. This study was funded by the Deutsche Forschungsgemeinschaft (DFG), the HOMFOR program and the Universität des Saarlandes.

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Authors and Affiliations

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

    Lucas Adrian, Matthias Lenski, Michael Böhm & Ulrich Laufs

  2. Institut für Biochemie und Molekulare Zellbiologie, Universitätsklinikum Hamburg-Eppendorf, 20246, Hamburg, Germany

    Klaus Tödter & Jörg Heeren

  3. Klinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, 04103, Leipzig, Germany

    Ulrich Laufs

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  1. Lucas Adrian
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Correspondence to Lucas Adrian.

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Adrian, L., Lenski, M., Tödter, K. et al. AMPK Prevents Palmitic Acid-Induced Apoptosis and Lipid Accumulation in Cardiomyocytes. Lipids 52, 737–750 (2017). https://doi.org/10.1007/s11745-017-4285-7

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  • DOI: https://doi.org/10.1007/s11745-017-4285-7

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