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Lipids

, Volume 52, Issue 9, pp 737–750 | Cite as

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

  • Lucas AdrianEmail author
  • Matthias Lenski
  • Klaus Tödter
  • Jörg Heeren
  • Michael Böhm
  • Ulrich Laufs
Original Article

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.

Keywords

Fatty acids Metabolism Nutrition 

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

Notes

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.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

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Copyright information

© AOCS 2017

Authors and Affiliations

  • Lucas Adrian
    • 1
    Email author
  • Matthias Lenski
    • 1
  • Klaus Tödter
    • 2
  • Jörg Heeren
    • 2
  • Michael Böhm
    • 1
  • Ulrich Laufs
    • 1
    • 3
  1. 1.Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische IntensivmedizinUniversitätsklinikum des SaarlandesHomburgGermany
  2. 2.Institut für Biochemie und Molekulare ZellbiologieUniversitätsklinikum Hamburg-EppendorfHamburgGermany
  3. 3.Klinik und Poliklinik für KardiologieUniversitätsklinikum LeipzigLeipzigGermany

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