Lucchinetti Eliana, Lou Phing-How, Chakravarty Akash, Marcolla Camila Schultz, Pauline Mirielle L, Wizzard Pamela R, Field Catherine J, Wine Eytan, Hersberger Martin, Wales Paul W, Turner Justine M, Krämer Stefanie D, Zaugg Michael
Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Alberta, Canada.
Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Alberta, Canada; Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada.
J Nutr. 2025 Mar;155(3):703-718. doi: 10.1016/j.tjnut.2024.10.047. Epub 2024 Nov 4.
Vegaven is a novel lipid emulsion for parenteral nutrition (PN) based on 18-carbon n-3 (ω-3) fatty acids, which elicits liver protection via interleukin-10 (IL-10) in the murine model of PN.
In a preclinical model of PN in neonatal piglets, Vegaven was tested for efficacy and safety and compared with a mixed-oil lipid emulsion containing fish oil (SMOFlipid).
Male piglets 4-5 d old were randomly allocated to isocaloric isonitrogenous PN for 14 d, which varied only by the type of lipid emulsion (Vegaven, n = 8; SMOFlipid, n = 8). Hepatic IL-10 tissue concentration served as primary outcome. Secondary outcomes were organ weights, bile flow, blood analyses, plasma insulin and glucagon concentrations, insulin signaling, proinflammatory cytokines, tissue lipopolysaccharide concentrations, and fatty acid composition of phospholipid fractions in plasma, liver, and brain.
Total weight gain on trial, organ weights, and bile flow were similar between the Vegaven and the SMOFlipid group. Vegaven elicited higher hepatic IL10 (Δ = 148 pg/mg protein; P < 0.001) and insulin receptor substrate-2 amounts (Δ = 0.08 OD; P = 0.012). Plasma insulin concentrations (Δ = 1.46 mU/L; P = 0.003) and fructosamine (glycated albumin, Δ = 12.4 μmol/g protein; P = 0.003) were increased in SMOFlipid as compared with those of Vegaven group, indicating insulin resistance. Higher hepatic injury markers were observed more frequently in the SMOFlipid group than those in the Vegaven group. Lipopolysaccharide, tumor necrosis factor-α, and IL-6 concentrations increased in pancreatic and brain tissues of SMOFlipid-treated compared with those in the Vegaven-treated piglets. Insulin signaling reduced in the brains of SMOFlipid-treated piglets. Vegaven and SMOFlipid elicited distinct fatty acid profiles in the phospholipid fractions of the rapidly growing brains but showed similar accretion of docosahexaenoic acid and arachidonic acid after 2 wk of PN.
Vegaven is well tolerated in this piglet model of PN, demonstrating distinct biological actions compared with SMOFlipid, namely lower liver, pancreas, and brain inflammation, enhanced insulin signaling, and improved whole body glucose control.
Vegaven是一种基于18碳n-3（ω-3）脂肪酸的新型肠外营养（PN）脂质乳剂，在PN小鼠模型中通过白细胞介素-10（IL-10）发挥肝脏保护作用。
在新生仔猪PN的临床前模型中，对Vegaven的疗效和安全性进行测试，并与含鱼油的混合油脂质乳剂（SMOFlipid）进行比较。
将4-5日龄雄性仔猪随机分配至等热量等氮的PN组，为期14天，仅脂质乳剂类型不同（Vegaven组，n = 8；SMOFlipid组，n = 8）。肝脏IL-10组织浓度作为主要观察指标。次要观察指标包括器官重量、胆汁流量、血液分析、血浆胰岛素和胰高血糖素浓度、胰岛素信号传导、促炎细胞因子、组织脂多糖浓度以及血浆、肝脏和脑组织中磷脂组分的脂肪酸组成。
Vegaven组和SMOFlipid组在试验期间的总体重增加、器官重量和胆汁流量相似。Vegaven组肝脏IL-10（Δ = 148 pg/mg蛋白；P < 0.001）和胰岛素受体底物-2含量更高（Δ = 0.08 OD；P = 0.012）。与Vegaven组相比，SMOFlipid组血浆胰岛素浓度（Δ = 1.46 mU/L；P = 0.003）和果糖胺（糖化白蛋白，Δ = 12.4 μmol/g蛋白；P = 0.003）升高，表明存在胰岛素抵抗。与Vegaven组相比，SMOFlipid组更频繁地观察到更高的肝损伤标志物。与Vegaven组处理的仔猪相比，SMOFlipid组处理的仔猪胰腺和脑组织中脂多糖、肿瘤坏死因子-α和IL-6浓度升高。SMOFlipid组处理的仔猪大脑中胰岛素信号传导降低。Vegaven和SMOFlipid在快速生长大脑的磷脂组分中引发了不同的脂肪酸谱，但在PN 2周后二十二碳六烯酸和花生四烯酸的蓄积相似。
在该仔猪PN模型中，Vegaven耐受性良好，与SMOFlipid相比具有独特的生物学作用，即肝脏、胰腺和脑部炎症更低、胰岛素信号增强以及全身血糖控制改善。
