Alpha-tocopherol in intravenous lipid emulsions imparts hepatic protection in a murine model of hepatosteatosis induced by the enteral administration of a parenteral nutrition solution

Intestinal failure-associated liver disease (IFALD) is a risk of parenteral nutrition (PN)-dependence. Intravenous soybean oil-based parenteral fat can exacerbate the risk of IFALD while intravenous fish oil can minimize its progression, yet the mechanisms by which soybean oil harms and fish oil protects the liver are uncertain. Properties that differentiate soybean and fish oils include α-tocopherol and phytosterol content. Soybean oil is rich in phytosterols and contains little α-tocopherol. Fish oil contains abundant α-tocopherol and little phytosterols. This study tested whether α-tocopherol confers hepatoprotective properties while phytosterols confer hepatotoxicity to intravenous fat emulsions. Utilizing emulsions formulated in the laboratory, a soybean oil emulsion (SO) failed to protect from hepatosteatosis in mice administered a PN solution enterally. An emulsion of soybean oil containing α-tocopherol (SO+AT) preserved normal hepatic architecture. A fish oil emulsion (FO) and an emulsion of fish oil containing phytosterols (FO+P) protected from steatosis in this model. Expression of hepatic acetyl CoA carboxylase (ACC) and peroxisome proliferator-activated receptor gamma (PPARγ), was increased in animals administered SO. ACC and PPARγ levels were comparable to chow-fed controls in animals receiving SO+AT, FO, and FO+P. This study suggests a hepatoprotective role for α-tocopherol in liver injury induced by the enteral administration of a parenteral nutrition solution. Phytosterols do not appear to compromise the hepatoprotective effects of fish oil.

肠功能衰竭相关性肝病（Intestinal failure-associated liver disease, IFALD）是肠外营养（parenteral nutrition, PN）依赖患者的潜在并发症风险。静脉输注的大豆油基肠外脂肪乳剂会加重IFALD的发病风险，而静脉鱼油乳剂则可延缓其病情进展，但大豆油损伤肝脏、鱼油保护肝脏的具体机制尚不明确。区分大豆油与鱼油的核心特性包括α-生育酚（α-tocopherol）与植物甾醇（phytosterol）的含量：大豆油富含植物甾醇，仅含少量α-生育酚；鱼油则富含α-生育酚，植物甾醇含量极低。本研究旨在验证α-生育酚是否可为静脉脂肪乳剂赋予肝保护特性，而植物甾醇是否会介导其肝毒性。本研究利用实验室自主配制的脂肪乳剂开展实验：经肠内给予肠外营养溶液的小鼠模型中，单纯大豆油乳剂（soybean oil emulsion, SO）未能改善肝脂肪变性；添加α-生育酚的大豆油乳剂（SO+AT）则可维持肝脏正常组织结构。鱼油乳剂（fish oil emulsion, FO）与添加植物甾醇的鱼油乳剂（FO+P）均可在该模型中对抗肝脂肪变性。在给予SO的小鼠肝脏组织中，乙酰辅酶A羧化酶（acetyl CoA carboxylase, ACC）与过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptor gamma, PPARγ）的表达水平显著升高；而在给予SO+AT、FO及FO+P的小鼠中，上述两种蛋白的表达水平与正常饲料喂养的对照组小鼠相当。本研究结果提示，α-生育酚在肠外营养溶液经肠内给药诱导的肝损伤中发挥明确的肝保护作用；而植物甾醇并未削弱鱼油的肝保护效应。