Superior liver protection in mice fed total parenteral nutrition containing the novel lipid emulsion Vegaven as compared to a mixed-oil lipid emulsion containing fish oil

Background: Mixed-oil lipid emulsion with plant-based 18-carbon n-3 fatty acids (Vegaven) elicits superior liver protection in total parenteral nutrition (TPN) compared with soybean oil-based or fish oil-based lipid emulsions. Objective: However, it is not known whether Vegaven is also superior to mixed-oil lipid emulsions containing longer-chain 20/22-carbon n-3 fatty acids derived from fish oil (SMOFlipid). Methods: Instrumented male C57BL/6NCrl mice (N=5) were subjected to a 7-day TPN with Vegaven (VEGA) or SMOFlipid (SMOF). Mice infused with 0.9% saline and free access to water and rodent diet served as controls. Tissue concentration of cytokines, indices of whole-body and hepatic glucose metabolism, markers of liver injury, and hepatic lipid mediators were measured. Results: Whole-body insulin resistance as measured by HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) values was lower in VEGA compared with SMOF and accompanied by higher glucagon and lower insulin plasma levels. The abundances of hepatic insulin receptor (IR), insulin receptor substrate 2 (IRS2) as well as the tyrosine phosphorylated IRS2 were higher in VEGA when compared with SMOF, fostering higher hepatic glycogen content. Tumor necrosis factor alpha and interleukin-6 (IL6) tissue concentrations were increased in livers of mice in the SMOF group and interleukin-6 (IL6) to interleukin-10 (IL10) ratios were lower in livers and epididymal white adipose tissue of mice in the VEGA group. Direct bilirubin plasma levels were elevated in SMOF, while ALT plasma levels were similar in all groups. Profiling of hepatic lipid mediators revealed the presence of α-linolenic acid-derived hydroxy-octadecatrienoic acid species exclusively in VEGA. Conclusions: TPN with Vegaven provides superior liver protection and whole-body blood glucose control than TPN with mixed-oil lipid emulsion containing fish oil in mice.