Abstract
Background and aims
The cardiovascular health benefits of eicosapentaenoic acid (EPA) have been demonstrated previously; however, the exact mechanism underlying them remains unclear. Our previous study found that lipotoxicity induced cardiomyocyte apoptosis via the inhibition of autophagy. Accordingly, in this study, we investigated whether EPA attenuated lipotoxicity-induced cardiomyocyte apoptosis through autophagy regulation. The role of EPA in mitochondrial dynamics was analyzed as well.
Methods
To explore how EPA protected against lipotoxicity-induced myocardial injury, cardiomyoblast (H9C2) cells were left untreated or were treated with 400 μM palmitic acid (PAM) and/or 80 μM EPA for 24 h.
Results
Excessive PAM treatment induced apoptosis. EPA reduced this PAM-induced apoptosis; however, EPA was unable to ameliorate the effects of PAM when autophagy was blocked by 3-methyladenine and bafilomycin A1. PAM blocked the autophagic flux, thus causing the accumulation of autophagosomes and acid vacuoles, whereas EPA restored the autophagic flux. PAM caused a decrease in polyunsaturated fatty acid (PUFA) content and an increase in saturated fatty acid content in the mitochondrial membrane, while EPA was incorporated in the mitochondrial membrane and caused a significant increase in the PUFA content. PAM also decreased the mitochondrial membrane potential, whereas EPA enhanced it. Finally, PAM elevated the expressions of autophagy-related proteins (LC3I, LC3II, p62) and mitochondrial fission protein (Drp1), whereas EPA inhibited their elevation under PAM treatment.
Conclusions
EPA reduces lipotoxicity-induced cardiomyoblast apoptosis through its effects on autophagy.
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Abbreviations
- Baf A1:
-
Bafilomycin A1
- EPA:
-
Eicosapentaenoic acid
- HFD:
-
High-fat diet
- 3-MA:
-
Methyladenine
- ∆ψ:
-
Mitochondrial membrane potential
- PAM:
-
Palmitic acid
- PUFA:
-
Polyunsaturated fatty acid
- SFA:
-
Saturated fatty acid
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Acknowledgements
This work was supported by the research grants MOST 104-2313-B-002-038-MY3 (from the Ministry of Science and Technology) and NTU-CESRP-104R7615-3 (from National Taiwan University). The authors are grateful to Miss Mai-Jun Lai and Miss Cian-Jyun Kao for their technical assistance.
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Hsu, HC., Li, SJ., Chen, CY. et al. Eicosapentaenoic acid protects cardiomyoblasts from lipotoxicity in an autophagy-dependent manner. Cell Biol Toxicol 34, 177–189 (2018). https://doi.org/10.1007/s10565-017-9406-9
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DOI: https://doi.org/10.1007/s10565-017-9406-9