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首页> 外文期刊>International Journal of Cardiology >PPARβ/δ attenuates palmitate-induced endoplasmic reticulum stress and induces autophagic markers in human cardiac cells
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PPARβ/δ attenuates palmitate-induced endoplasmic reticulum stress and induces autophagic markers in human cardiac cells

机译：PPARβ/δ减轻棕榈酸酯诱导的内质网应激并诱导人心肌细胞自噬标记

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Background Chronic endoplasmic reticulum (ER) stress contributes to the apoptotic cell death in the myocardium, thereby playing a critical role in the development of cardiomyopathy. ER stress has been reported to be induced after high-fat diet feeding in mice and also after saturated fatty acid treatment in vitro. Therefore, since several studies have shown that peroxisome proliferator-activated receptor (PPAR)β/δ inhibits ER stress, the main goal of this study consisted in investigating whether activation of this nuclear receptor was able to prevent lipid-induced ER stress in cardiac cells. Methods and results Wild-type and transgenic mice with reduced PPARβ/δ expression were fed a standard diet or a high-fat diet for two months. For in vitro studies, a cardiomyocyte cell line of human origin, AC16, was treated with palmitate and the PPARβ/δ agonist GW501516. Our results demonstrate that palmitate induced ER stress in AC16 cells, a fact which was prevented after PPARβ/δ activation with GW501516. Interestingly, the effect of GW501516 on ER stress occurred in an AMPK-independent manner. The most striking result of this study is that GW501516 treatment also upregulated the protein levels of beclin 1 and LC3II, two well-known markers of autophagy. In accordance with this, feeding on a high-fat diet or suppression of PPARβ/δ in knockout mice induced ER stress in the heart. Moreover, PPARβ/δ knockout mice also displayed a reduction in autophagic markers. Conclusion Our data indicate that PPARβ/δ activation might be useful to prevent the harmful effects of ER stress induced by saturated fatty acids in the heart by inducing autophagy.
机译：背景慢性内质网（ER）应激会导致心肌细胞凋亡，从而在心肌病的发展中起关键作用。据报道，高脂饮食喂养小鼠和体外饱和脂肪酸治疗后，会诱发内质网应激。因此，由于数项研究表明过氧化物酶体增殖物激活受体（PPAR）β/δ抑制内质网应激，因此本研究的主要目标在于调查该核受体的活化是否能够预防脂质诱导的心肌细胞内质网应激。 。方法和结果给PPARβ/δ表达降低的野生型和转基因小鼠喂食标准饮食或高脂饮食两个月。为了进行体外研究，用棕榈酸酯和PPARβ/δ激动剂GW501516处理了人类来源的心肌细胞系AC16。我们的结果证明棕榈酸酯诱导AC16细胞中的内质网应激，这一事实在GW501516激活PPARβ/δ后被阻止。有趣的是，GW501516对内质网应激的影响以与AMPK无关的方式发生。这项研究最令人惊讶的结果是，GW501516处理还上调了自噬的两个著名标志物beclin 1和LC3II的蛋白质水平。据此，以高脂饮食为食或在敲除小鼠中抑制PPARβ/δ可引起心脏的内质网应激。此外，PPARβ/δ基因敲除小鼠的自噬标志物也减少。结论我们的数据表明，PPARβ/δ激活可能通过诱导自噬来预防饱和脂肪酸对心脏的内质网应激的有害作用。

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