The novel lipid emulsion Vegaven is well tolerated and elicits distinct biological actions compared with a mixed-oil lipid emulsion containing fish oil:a parenteral nutrition trial in piglets.

Abstract

Background: Vegaven is a novel lipid emulsion for parenteral nutrition (PN) based on 18-carbon n-3 fatty acids, which elicits liver protection via interleukin-10 (IL10) in the murine model of PN.

Objective: 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).

Methods: 4-5-day-old male piglets were randomly allocated to isocaloric isonitrogenous PN for 14 days that varied only by the type of lipid emulsion (Vegaven, N=8; SMOFlipid, N=8). Hepatic IL10 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.

Results: 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 levels (Δ=0.08 O.D., 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 Vegaven group, indicating insulin resistance. Higher hepatic injury markers were observed more frequently in the SMOFlipid group compared with the Vegaven group. Lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-6 were increased in pancreatic and brain tissues of SMOFlipid- vs Vegaven-treated piglets. Insulin signaling was 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 two weeks of PN.

Conclusions: Vegaven was well tolerated in this piglet model of PN and demonstrated distinct biological actions compared with SMOFlipid, namely lower liver, pancreas, and brain inflammation, enhanced insulin signaling, and improved whole-body glucose control.