Vascular Biology Program and Department of Surgery.
Robert Wood Johnson Medical School, Piscataway, NJ.
Am J Clin Nutr. 2019 Apr 1;109(4):1038-1050. doi: 10.1093/ajcn/nqy370.
Fish oil (FO) intravenous lipid emulsions (ILEs) are used as a monotherapy to treat parenteral nutrition (PN)-associated liver disease and provide essential fatty acids (EFAs) needed to sustain growth and prevent EFA deficiency (EFAD). Studies have suggested that medium-chain triglycerides (MCTs) and α-tocopherol have anti-inflammatory properties.
The purpose of this study was to test whether FO-ILEs containing MCTs and/or additional α-tocopherol decrease the inflammatory response to an endotoxin challenge compared with FO-ILE alone and preserve the ability to prevent PN-induced liver injury in mice.
A murine model of PN-induced hepatosteatosis was used to compare the effects of ILEs formulated in the laboratory containing varying ratios of FO and MCTs, and subsequently FO- and 50:50 FO:MCT-ILE plus 500 mg/L α-tocopherol (FO + AT and 50:50 + AT, respectively). C57BL/6 mice receiving unpurified diet (UPD), PN-equivalent diet (PN) + saline, and PN + soybean oil (SO)-ILE served as controls. After 19 d, mice received an intraperitoneal saline or endotoxin challenge 4 h before being killed. Serum and livers were harvested for histologic analysis, fatty acid profiling, and measurement of systemic inflammatory markers (tumor necrosis factor-α, interleukin-6).
All ILEs were well tolerated and prevented biochemical EFAD. Livers of mice that received saline and SO developed steatosis. Mice that received 30:70 FO:MCT developed mild hepatosteatosis. All other FO-containing ILEs preserved normal hepatic architecture. Mice that received FO- or SO-ILE had significantly elevated systemic inflammatory markers after endotoxin challenge compared with UPD-fed controls, whereas 50:50 FO:MCT, 30:70 FO:MCT, FO + AT, and 50:50 + AT groups had significantly lower inflammatory markers similar to those seen in UPD-fed controls.
Mixed FO/MCT and the addition of α-tocopherol to FO improved the inflammatory response to endotoxin challenge compared with FO-ILE alone while still preventing PN-induced liver injury and EFAD in mice. There was no synergistic relation between α-tocopherol and MCTs.
鱼油（FO）静脉内脂肪乳剂（ILE）被用作单一疗法来治疗肠外营养（PN）相关的肝病，并提供维持生长和预防必需脂肪酸缺乏（EFAD）所需的必需脂肪酸（EFAs）。研究表明，中链甘油三酯（MCT）和α-生育酚具有抗炎特性。
本研究旨在测试含有 MCT 和/或额外α-生育酚的 FO-ILE 是否能降低内毒素挑战引起的炎症反应，与单独使用 FO-ILE 相比，并保持预防小鼠 PN 诱导的肝损伤的能力。
使用 PN 诱导的肝脂肪变性的小鼠模型来比较实验室中含有不同比例 FO 和 MCT 的 ILE 的作用，随后是 FO 和 50:50 FO:MCT-ILE 加 500mg/Lα-生育酚（FO+AT 和 50:50+AT，分别）。接受未纯化饮食（UPD）、PN 等效饮食（PN）+盐水和 PN+大豆油（SO）-ILE 的 C57BL/6 小鼠作为对照。19 天后，在处死前 4 小时，小鼠接受腹腔内盐水或内毒素挑战。采集血清和肝脏进行组织学分析、脂肪酸谱分析和测量全身炎症标志物（肿瘤坏死因子-α、白细胞介素-6）。
所有 ILE 均耐受良好，预防了生化 EFAD。接受盐水和 SO 的小鼠肝脏发生脂肪变性。接受 30:70 FO:MCT 的小鼠发生轻度肝脂肪变性。所有其他含有 FO 的 ILE 均保持正常的肝结构。与 UPD 喂养的对照组相比，接受 FO 或 SO-ILE 的小鼠在接受内毒素挑战后，全身炎症标志物显著升高，而 50:50 FO:MCT、30:70 FO:MCT、FO+AT 和 50:50+AT 组的炎症标志物显著降低，与 UPD 喂养的对照组相似。
与单独使用 FO-ILE 相比，混合 FO/MCT 和在 FO 中添加α-生育酚可改善对内毒素挑战的炎症反应，同时仍能预防小鼠的 PN 诱导的肝损伤和 EFAD。α-生育酚和 MCT 之间没有协同关系。
