Monounsaturated fatty acids protect against palmitate-induced lipoapoptosis in human umbilical vein endothelial cells
Monounsaturated fatty acids protect against palmitate-induced lipoapoptosis in human umbilical vein endothelial cells
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DOI：
10.1371/journal.pone.0226940
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发表时间：
2019-12-31
期刊：
影响因子：
3.7
通讯作者：
Gentile, Christopher L.
中科院分区：
文献类型：
--
作者：
Lee, Dustin M.;Sevits, Kyle J.;Gentile, Christopher L.
富含饱和脂肪酸的饮食与心血管疾病风险增加有关，而单不饱和脂肪酸与改善心血管结局有关。因此，细胞培养研究表明，饱和脂肪酸，特别是长链饱和脂肪酸，例如棕榈酸酯，可诱导多种细胞类型的功能障碍和细胞死亡，而单不饱和脂肪酸可以提供针对棕榈酸酯介导的损伤的保护。本研究的目的是检查单不饱和脂肪酸是否可以防止内皮细胞中棕榈酸酯介导的细胞死亡，以确定 AMPK 失活和激活（分别通过化合物 C 和 AICAR）是否是棕榈酸酯诱导的损伤和单不饱和脂肪酸介导的保护的基础，并探讨 ER 应激在这方面的作用。单独用棕榈酸酯（0.25和0.5mM）或与单不饱和脂肪酸油酸酯或棕榈油酸酯（0.25和0.5mM）、AICAR、化合物C、4μ8C或TUDCA组合处理24小时后，检查人脐静脉内皮细胞的细胞活力和细胞凋亡。与对照细胞相比，棕榈酸以剂量依赖性方式显着降低细胞活力并增加细胞凋亡。单不饱和脂肪酸油酸酯和棕榈油酸酯完全阻止了棕榈酸酯的细胞毒性作用。尽管棕榈酸诱导内质网应激标志物，但化学抑制内质网应激并不能阻止棕榈酸诱导的脂肪细胞凋亡。相反，AMPK激活剂AICAR（0.1和0.5mM）可防止棕榈酸酯介导的活力、细胞凋亡和内质网应激改变，而AMPK抑制剂化合物C（20和40μM）则显着加剧棕榈酸酯介导的损伤。最后，与棕榈酸酯、单不饱和脂肪酸和化合物 C 共孵育显着减轻了油酸酯和棕榈油酸酯的保护作用。总之，单不饱和脂肪酸可以保护血管内皮细胞免受棕榈酸酯的细胞毒性作用；和棕榈酸介导的损伤以及单不饱和介导的保护分别部分归因于代谢调节剂 AMPK 的失活和激活。这些结果可能有助于了解高饱和脂肪饮食对心血管功能障碍和疾病风险的有害影响。
Diets high in saturated fatty acids are linked to increased cardiovascular disease risk, whereas monounsaturated fatty acids have been associated with improved cardiovascular outcomes. Accordingly, cell culture studies have demonstrated that saturated fatty acids, particularly long chain saturated fatty acids such as palmitate, induce dysfunction and cell death in a variety of cell types, and monounsaturated fatty acids may confer protection against palmitate-mediated damage. The aim of the present study was to examine whether monounsaturated fatty acids could protect against palmitate-mediated cell death in endothelial cells, to determine if AMPK inactivation and activation (via compound C and AICAR, respectively) underlies both palmitate-induced damage and monounsaturated fatty acid mediated protection, and to explore the role of ER stress in this context. Human umbilical vein endothelial cells were examined for cell viability and apoptosis following treatment for 24 hours with palmitate (0.25 and 0.5mM) alone or in combination with the monounsaturated fatty acids oleate or palmitoleate (0.25 and 0.5mM), AICAR, compound C, 4 mu 8C, or TUDCA. Compared to control cells, palmitate significantly decreased cell viability and increased apoptosis in a dose-dependent manner. The monounsaturated fatty acids oleate and palmitoleate completely prevented the cytotoxic effects of palmitate. Although palmitate induced markers of ER stress, chemical inhibition of ER stress did not prevent palmitate-induced lipoapoptosis. Conversely, the AMPK activator AICAR (0.1 and 0.5mM) conferred protection from palmitate mediated-alterations in viability, apoptosis and ER stress, whereas the AMPK inhibitor compound C (20 and 40 mu M) significantly exacerbated palmitate-mediated damage. Lastly, co-incubation with palmitate, monounsaturated fatty acids, and compound C significantly mitigated the protective effects of both oleate and palmitoleate. In conclusion, monounsaturated fatty acids confer protection against the cytotoxic effects of palmitate in vascular endothelial cells; and palmitate-mediated damage, as well as monounsaturated-mediated protection, are due in part to inactivation and activation, respectively, of the metabolic regulator AMPK. These results may have implications for understanding the deleterious effects of high saturated fat diets on cardiovascular dysfunction and disease risk.