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High-fat diet induces cardiomyocyte apoptosis via the inhibition of autophagy

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European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

Excessive fat intake induces obesity and causes cardiac injury. Intracellular degradation process involving destruction of long-lived proteins and organelles maintains homeostasis for cells under stress. The purpose of this study was to explore the relation of high-fat diet (HFD)-induced cardiac injury and intracellular degradation process with regard to autophagy and ER stress.

Methods and results

HFD feeding for 24 weeks induced hyperglycemia, hyperlipidemia, and cardiac hypertrophy in adult male C57BL/6 mice. In the heart, PARP cleavage, an indicator of apoptosis, levels of LC3-II and p62, indicators of autophagy, and CHOP, indicator of ER stress, were increased. A palmitate-treated cardiomyoblast (H9C2) cell culture was examined to explore how HFD induced myocardial injury. Excessive palmitate (400 μM) treatment induced apoptosis and increased the number of autophagosomes and acid vacuoles of H9C2 cells. Besides, it elevated the expression of LC3-II, p62, and PARP cleavage. Induction of autophagy by rapamycin ameliorated palmitate-induced apoptosis, while inhibition of autophagy by 3-methyladenine or LC3 siRNA exacerbated palmitate-induced apoptosis. Palmitate treatment also induced CHOP expression which is associated with ER stress.

Conclusion

HFD can cause cardiac injury by induction of apoptosis which is associated with autophagy dysregulation and ER stress. In addition, autophagy deficiency augments cardiac apoptosis, suggesting that autophagy serves as a pro-survival role in lipotoxic condition.

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Acknowledgments

This study was supported in part by Grant NSC 101-2313-B-002-030-MY3, NSC 101-2314-B-002-187-MY3, and MOST 103-2313-B-002-035 from the Ministry of Science and Technology, Taiwan. The authors are grateful to Miss Mai-Jun Lai and Miss Cian-Jyun Kao for their technical assistance.

Authors’ contributions

Hsu C. H. carried out the studies and data analyses and drafted the manuscript. Chen C. Y. conceived the study, participated in its design and coordination, and helped to draft the manuscript. Lee B. C. carried out the animal studies and data analyses. Chen M. F. obtained funding and supervised the study. All authors read and approved the final manuscript.

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Author notes

  1. Ching-Yi Chen

    Present address: Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei 112, 10673, Taiwan

Authors and Affiliations

  1. Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan S Rd, Taipei, Taiwan

    Hsiu-Ching Hsu, Bai-Chin Lee & Ming-Fong Chen

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Correspondence to Ching-Yi Chen.

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Hsu, HC., Chen, CY., Lee, BC. et al. High-fat diet induces cardiomyocyte apoptosis via the inhibition of autophagy. Eur J Nutr 55, 2245–2254 (2016). https://doi.org/10.1007/s00394-015-1034-7

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  • DOI: https://doi.org/10.1007/s00394-015-1034-7

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