Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
JPEN J Parenter Enteral Nutr. 2019 Jul;43(5):668-676. doi: 10.1002/jpen.1437. Epub 2018 Aug 23.
Neonates with intestinal failure dependent on parenteral nutrition (PN) are at risk of intestinal failure-associated liver disease (IFALD). PN lipid composition relates to the risk of IFALD, but the mechanisms are poorly understood. We investigated the effects of soybean oil (SO), a mixed-lipid (ML) emulsion containing fish oil (FO), and a pure FO. We hypothesized FO-containing PN lipids would result in increased gene expression of canalicular bile acid transporters and a larger, more hydrophilic bile acid pool, predictive of increased bile flow.
Neonatal piglets were allocated to receive 1 of SO, ML, or FO throughout 14 days of PN feeding. Relative expression of genes involved in bile acid synthesis and transport were determined through quantitative polymerase chain reaction. Bile secreted from the liver was collected and measured. Bile acid composition was determined using tandem mass spectrometry. Regression analysis was used to determine predictors of bile flow.
PN reduced bile acid secretion (P < .001). FO-containing PN lipids were associated with greater expression of bile acid and organic solute transport genes (P < .05) and greater secretion of hydrophobic bile acids (P < .001). Farnesoid X receptor (P = .01), bile salt export pump (P < .01), multidrug resistant protein 2 (P < .01), and unconjugated hyocholic acid (P < .001) independently predicted bile flow.
PN lipid modulation altered bile acid metabolism and composition. These alterations may explain the hepatoprotective effects of FO-containing PN lipids and support their use in the prevention and treatment of IFALD.
依赖于肠外营养（PN）的肠衰竭新生儿有发生肠衰竭相关肝病（IFALD）的风险。PN 脂质组成与 IFALD 的风险相关，但机制尚不清楚。我们研究了大豆油（SO）、含有鱼油（FO）的混合脂质（ML）乳液和纯 FO 的作用。我们假设含有 FO 的 PN 脂质会导致胆小管胆汁酸转运体的基因表达增加，并产生更大、更亲水的胆汁酸池，这预示着胆汁流量增加。
将新生仔猪分配接受 SO、ML 或 FO 中的 1 种 PN 喂养 14 天。通过定量聚合酶链反应确定参与胆汁酸合成和转运的基因的相对表达。从肝脏收集和测量分泌的胆汁。使用串联质谱法确定胆汁酸组成。回归分析用于确定胆汁流量的预测因子。
PN 降低了胆汁酸分泌（P<0.001）。含有 FO 的 PN 脂质与胆汁酸和有机溶质转运基因的表达增加相关（P<0.05），并与疏水性胆汁酸的分泌增加相关（P<0.001）。法尼醇 X 受体（P=0.01）、胆汁盐输出泵（P<0.01）、多药耐药蛋白 2（P<0.01）和未结合的胆酸（P<0.001）独立预测了胆汁流量。
PN 脂质调节改变了胆汁酸代谢和组成。这些改变可能解释了含有 FO 的 PN 脂质的肝保护作用，并支持其用于预防和治疗 IFALD。
