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Monounsaturated 14:1n-9 and 16:1n-9 Fatty Acids but not 18:1n-9 Induce Apoptosis and Necrosis in Murine HL-1 Cardiomyocytes

  • Original Article
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Lipids

Abstract

Patients with inborn errors of long-chain fatty acid oxidation accumulate disease-specific acylcarnitines and triacylglycerols in various tissues. Some of these patients present significant cardiac diseases such as arrhythmias and cardiomyopathy. The mechanism of how fatty acid accumulation is involved in disease pathogenesis is still unclear but apoptosis of cardiomyocytes has been suggested to be one possible mechanism of cardiomyopathy development. In this study, we measured lipid uptake and intracellular lipid accumulation after incubation of HL1 cardiomyocytes with different saturated and monounsaturated long- and medium-chain fatty acid species for various time periods and at different physiological concentrations. We assessed apoptosis induction by analyzing the mitochondrial membrane potential and TLR-4 expression as well as the composition of the accumulating triacylglycerols. We identified only 14:1 and 16:1 monounsaturated fatty acids potentially leading to an increase in TLR-4 expression and disruption of the mitochondrial membrane potential, resulting in apoptosis and necrosis in cultured cardiomyocytes. This study demonstrates significant toxicity of especially those fatty acid species in vitro that significantly accumulate in fatty acid oxidation defects presenting with cardiac disease such as very long-chain acyl-CoA dehydrogenase, carnitine acylcarnitine translocase and carnitine palmitoyl-CoA transferase deficiencies.

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Abbreviations

CACT:

Carnitine/acylcarnitine translocase

CDDE:

Cell death detection ELISA

ELISA:

Enzyme linked immunosorbent assay

FACS:

Fluorescence activated cell sorting

FCS:

Fetal calf serum

FFA:

Free fatty acid(s)

HMGB:

High mobility group binding protein

LDH:

Lactate dehydrogenase

MMP:

Mitochondrial membrane potential

MCAD:

Medium-chain-acyl-CoA-dehydrogenase

mRNA:

Messenger ribonucleic acid

PBS:

Phosphate buffered saline

PCR:

Polymerase chain reaction

PGC-1α:

Peroxisome proliferator activated receptor-gamma coactivator 1 alpha

PPAR-α:

Peroxisome proliferator activated receptor-alpha

PDK4:

Pyruvate dehydrogenase kinase 4

TLR-4:

Toll-like receptor 4

UPLC-MS/MS:

Ultra pressure liquid chromatography tandem mass spectrometry

VLCAD:

Very long-chain-acyl-CoA-dehydrogenase

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Acknowledgments

The study was supported by grants from the Deutsche Forschungsgemeinschaft (SFB 575 and SFB 612 Heinrich Heine University Duesseldorf).

Conflict of interest

Nothing to disclose.

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Authors and Affiliations

  1. Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children’s Hospital, Moorenstrasse 5, 40225, Duesseldorf, Germany

    Lars Hoffmann, Annette Seibt, Diran Herebian & Ute Spiekerkoetter

  2. Department of General Pediatrics, University Children’s Hospital, Freiburg, Germany

    Ute Spiekerkoetter

Authors
  1. Lars Hoffmann
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  2. Annette Seibt
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  3. Diran Herebian
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  4. Ute Spiekerkoetter
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Correspondence to Lars Hoffmann.

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Hoffmann, L., Seibt, A., Herebian, D. et al. Monounsaturated 14:1n-9 and 16:1n-9 Fatty Acids but not 18:1n-9 Induce Apoptosis and Necrosis in Murine HL-1 Cardiomyocytes. Lipids 49, 25–37 (2014). https://doi.org/10.1007/s11745-013-3865-4

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  • DOI: https://doi.org/10.1007/s11745-013-3865-4

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