Excessive consumption of saturated fat leads to non-alcoholic fatty liver disease (NAFLD), which is attenuated by supplementation of n-3 polyunsaturated fatty acids (PUFAs). Endoplasmic reticulum (ER) stress is crucial in the development of NAFLD, but how high-saturated fat diet (HFD) causes ER stress and NAFLD remains unclear. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in hepatic ER stress. We aimed to explore the roles of LOX-1 in HFD-induced ER stress. Male Sprague–Dawley rats were fed an HFD without or with supplementation of fish oil for 16 weeks. The effects of n-3 PUFAs on hepatic ER stress degrees and the expression levels of LOX-1 were examined. Then human L02 hepatoma cells were treated with palmitate or palmitate and DHA to determine the ER stress and LOX-1 expression levels in vitro. After that the expression of LOX-1 in L02 cells was either knocked-down or overexpressed to analyze the roles of LOX-1 in palmitate-induced ER stress. The feeding of HFD induced NAFLD development and ER stress in the liver, and LOX-1 expressing level, which were all reversed by fish oil supplementation. In vitro, DHA treatment reduced the expression of LOX-1, and palmitate-induced ER stress. SiRNA-mediated knock-down of LOX-1 inhibited palmitate-induced ER stress, whereas overexpression of LOX-1 dramatically induced ER stress in L02 cells.LOX-1 is critical for HFD-induced ER stress, and inhibition of its expression under the treatment of n-3 PUFAs could ameliorate HFD-induced NAFLD.

过量摄入饱和脂肪会导致非酒精性脂肪性肝病 (NAFLD)，而补充 n-3 多不饱和脂肪酸 (PUFA) 可减轻这种情况。内质网 (ER) 应激在 NAFLD 的发展中至关重要，但高饱和脂肪饮食 (HFD) 如何导致 ER 应激和 NAFLD 尚不清楚。凝集素样氧化低密度脂蛋白受体-1 (LOX-1) 参与肝脏内质网应激。我们旨在探索 LOX-1 在 HFD 诱导的内质网应激中的作用。雄性 Sprague-Dawley 大鼠在不补充鱼油或不补充鱼油的情况下喂食 HFD 16 周。检查n-3 PUFAs对肝脏ER应激程度和LOX-1表达水平的影响。然后用棕榈酸酯或棕榈酸酯和DHA处理人L02肝癌细胞以确定ER应激和LOX-1表达水平体外。之后 L02 细胞中 LOX-1 的表达被敲低或过表达，以分析 LOX-1 在棕榈酸酯诱导的 ER 应激中的作用。喂食HFD诱导肝脏中NAFLD的发展和ER应激，以及LOX-1的表达水平，这些都被鱼油补充逆转。在体外，DHA 处理降低了 LOX-1 的表达和棕榈酸酯诱导的内质网应激。SiRNA 介导的 LOX-1 敲低抑制了棕榈酸酯诱导的内质网应激，而 LOX-1 的过表达显着诱导了 L02 细胞中的内质网应激。 LOX-1 对 HFD 诱导的内质网应激至关重要，并且在n-3 PUFA 的治疗可以改善 HFD 诱导的 NAFLD。