Clinical Veterinary Medicine, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China.
J Cell Physiol. 2020 Sep;235(9):6246-6256. doi: 10.1002/jcp.29553. Epub 2020 Feb 3.
To evaluate the effects of fatty acids on endoplasmic reticulum (ER) stress, oxidative stress, and lipid damage. We treated BRL3A rat liver cells with, linoleic (LA), linolenic, oleic (OA), palmitic (PA), palmitoleic (POA), or stearic (SA) acid for 12 hr. The characteristics of cell lipid deposition, oxidative stress indexes, ER stress markers, nuclear factor κB p65 (NF-κB p65), lipid synthesis and transport regulators, and cholesterol metabolism regulators were analyzed. Endoplasmic chaperones like glucose-regulated protein 78, CCAAT-enhancer-binding protein, NF-κB p65, hydrogen peroxide, and malonaldehyde in PA- and SA-treated cells were significantly higher than in other treated cells. Deposition of fatty acids especially LA and POA were significantly increased than in other treated cells. De novo lipogenesis regulators sterol regulatory element-binding protein 1c, fatty acid synthase, and acetyl-coenzyme A carboxylase 1 (ACC1) expression were significantly increased in all fatty acid stimulation groups, and PA- and SA-treated cells showed lower p-ACC1 expression and higher scd1 expression than other fatty acid groups. Very low-density lipoprotein synthesis and apolipoprotein B100 expression in free fatty acids treated cells were significantly lower than control. PA, SA, OA, and POA had shown significantly increased cholesterol synthesis than other treated cells. PA and SA showed the lower synthesis of cytochrome P7A1 and total bile acids than other fatty acids treated cells. Excess of saturated fatty acids led to severe ER and oxidative stress. Excess unsaturated fatty acids led to increased lipid deposition in cultured hepatocytes. A balanced fatty acid intake is needed to maintain lipid homeostasis.
为了评估脂肪酸对内质网（ER）应激、氧化应激和脂质损伤的影响。我们用亚油酸（LA）、亚麻酸、油酸（OA）、棕榈酸（PA）、棕榈油酸（POA）或硬脂酸（SA）处理 BRL3A 大鼠肝细胞 12 小时。分析细胞脂质沉积、氧化应激指标、内质网应激标志物、核因子κB p65（NF-κB p65）、脂质合成和转运调节剂以及胆固醇代谢调节剂的特征。PA 和 SA 处理细胞中的葡萄糖调节蛋白 78、CCAAT 增强子结合蛋白、NF-κB p65、过氧化氢和丙二醛等内质网伴侣明显高于其他处理细胞。脂肪酸特别是 LA 和 POA 的沉积明显高于其他处理细胞。所有脂肪酸刺激组的固醇调节元件结合蛋白 1c、脂肪酸合成酶和乙酰辅酶 A 羧化酶 1（ACC1）的从头脂肪生成调节剂表达均显著增加，PA 和 SA 处理细胞的 p-ACC1 表达较低，scd1 表达较高与其他脂肪酸组相比。游离脂肪酸处理细胞中的极低密度脂蛋白合成和载脂蛋白 B100 表达明显低于对照。PA、SA、OA 和 POA 显示出比其他处理细胞更高的胆固醇合成。PA 和 SA 显示出比其他脂肪酸处理细胞更低的细胞色素 P7A1 和总胆汁酸合成。过量的饱和脂肪酸导致内质网和氧化应激严重。过量的不饱和脂肪酸导致培养的肝细胞中脂质沉积增加。需要平衡的脂肪酸摄入来维持脂质稳态。
