High-fat diet induces cardiomyocyte apoptosis via the inhibition of autophagy
High-fat diet induces cardiomyocyte apoptosis via the inhibition of autophagy
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DOI：
10.1007/s00394-015-1034-7
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发表时间：
2016-10-01
影响因子：
5
通讯作者：
Chen, Ming-Fong
中科院分区：
文献类型：
--
作者：
Hsu, Hsiu-Ching;Chen, Ching-Yi;Chen, Ming-Fong
过多的脂肪摄入会导致肥胖，并导致心脏损伤。细胞内降解过程包括破坏长寿命的蛋白质和细胞器，维持细胞在应激状态下的动态平衡。本研究旨在探讨高脂饮食(HFD)诱导的心肌损伤与细胞内降解过程与自噬和内质网应激的关系。高脂饲料喂养24周可引起成年雄性C57BL/6小鼠高血糖、高脂血症和心肌肥大。在心脏中，作为细胞凋亡指标的PARP裂解、自噬指标Lc3-II和p62的水平以及内质网应激指标CHOP的水平均增加。以棕榈酸酯处理的心肌母细胞(H9C2)为研究对象，探讨HFD对心肌的损伤作用。过量棕榈酸酯(400 MU M)处理可诱导H9C2细胞凋亡，并增加自噬小体和酸性空泡的数量。此外，它还上调了Lc3-II、p62和PARP的表达。雷帕霉素诱导的自噬减轻棕榈酸酯诱导的细胞凋亡，而3-甲基腺嘌呤或LC3siRNA抑制自噬加剧棕榈酸酯诱导的细胞凋亡。棕榈酸酯处理还诱导CHOP的表达，这与内质网应激有关。HFD可通过诱导细胞凋亡而导致心脏损伤，这与自噬、调节失调和内质网应激有关。此外，自噬缺陷增加了心肌细胞的凋亡，这表明自噬在脂毒状态下起着促进生存的作用。
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.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 mu M) 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.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.