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Clinical Nutrition (Poster Session)

(P03-065-24) A Novel Lipid Emulsion Containing 18-Cn3 Fatty Acids Demonstrates Superior Liver Protection to SMOFlipid® in the Murine Model of Parenteral Nutrition

Sunday, June 30, 2024
12:45 PM – 1:45 PM CT
Location: Poster Board 220
Disclosure(s):
Michael Zaugg, MD FRCPC MBA: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: The mixed-oil lipid emulsion with plant-based C-18n-3 fatty acids Vegaven® (VV) elicits superior liver protection compared with soybean oil-based Intralipid® or fish oil-based Omegaven® in the murine model of parenteral nutrition (PN) [1]. However, it is not known whether VV is also superior to mixed-oil lipid emulsions such as SMOFlipid® (SL) containing longer-chain C-20/22n-3 fatty acids.

Methods: Instrumented male C57BL/6 mice were subjected to a 7-day PN with VV or SL or saline infusion with chow feeding (control) prior to analysis of liver cytokines, indices of whole-body and hepatic glucose metabolism, markers of liver injury, and hepatic lipid mediators.

Results: Whole-body insulin resistance as measured by HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) values was lower in VV-PN compared with SL-PN mice and accompanied by higher glucagon-like peptide 1 and lower insulin plasma levels. VV-PN elevated the abundance of hepatic insulin receptor (IR), insulin receptor substrate 2 (IRS-2) as well as the Y-phosphorylation of IRS-2 compared with SL-PN, fostering higher hepatic glycogen contents. TNFalpha and C-reactive protein tissue concentrations were increased in livers of SL-PN mice compared with VV-PN mice. Interleukin-6 to interleukin-10 ratios were lower in livers and white adipose tissues of VV-PN mice. Direct bilirubin plasma levels were elevated in SL-PN mice compared with VV-PN mice. Profiling of hepatic lipid mediators revealed the presence of alpha-linolenic acid-derived hydroxy-octadecatrienoic acid species predominantly in VV-PN mice. The presence of additional octadecanoids such as 12-HOTrE, 15-HOTrE, 16-HOTrE, and 13-HODE-ALA could be also confirmed in livers of VV-PN mice.

Conclusions: PN with Vegaven®, a mixed-oil lipid emulsion with C-18n-3 fatty acids, provides superior liver protection than PN with SMOFlipid®, a mixed-oil lipid emulsion with C-20/22n-3 fatty acids, in a murine model.

Disclosure: EP 21/204659.3 (patent application)

Reference:

[1] Lucchinetti et al. Am J Clin Nutr. 2022;116(6):1805-1819. doi: 10.1093/ajcn/nqac272. PMID: 36166844

Funding Sources: Crohn's and Colitis Canada