Endothelial Barrier Disruption by Lipid Emulsions Containing a High Amount of N3 Fatty Acids (Omegaven) but Not N6 Fatty Acids (Intralipid)

Cells. 2022 Jul 14;11(14):2202. doi: 10.3390/cells11142202.

Abstract

Lipid emulsions are crucial for life-saving total parenteral nutrition (TPN). Their composition provides a high amount of essential fatty acids and calories for millions of patients with serious diseases. Nevertheless, several TPN-mediated side-effects have been reported in over 90% of patients. This project aimed to investigate the effect of a high amount of ω3 fatty acids (Omegaven®) emulsion vs. a high amount of ω6 fatty acids (Intralipid®) emulsions on the endothelial barrier function. EA.hy926 cell line was cultured and incubated with 0.01, 0.1, and 1 mM lipid emulsions. The influence of these lipid emulsions on the barrier function was assessed using ECIS technology, immunofluorescent microscopy, viability measurements by flow cytometry, multiplex cytokines analysis, and qRT-PCR. BODIPY staining confirmed the uptake of fatty acids by endothelial cells. ECIS measurements demonstrated that a high concentration of Omegaven® prevents barrier formation and impairs the barrier function by inducing cell detachment. Moreover, the expression of VE-cadherin and F-actin formation showed a reorganization of the cell structure within 2 h of 1 mM Omegaven® addition. Interestingly, the study's findings contradict previous studies and revealed that Omegaven® at high concentration, but not Intralipid, induces cell detachments, impairing endothelial cells' barrier function. In summary, our studies shed new light on the effect of lipid emulsions on the endothelium.

Keywords: endothelial barrier; endothelial cells; lipid emulsions; parenteral nutrition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Emulsions / pharmacology
  • Endothelial Cells / metabolism
  • Endothelium / metabolism
  • Fatty Acids* / metabolism
  • Fatty Acids* / pharmacology
  • Fatty Acids, Omega-3* / pharmacology
  • Fish Oils
  • Humans
  • Triglycerides

Substances

  • Emulsions
  • Fatty Acids
  • Fatty Acids, Omega-3
  • Fish Oils
  • Triglycerides
  • fish oil triglycerides

Grants and funding

This work was supported by the grant from the Swiss Science Foundation (Sinergia grant nr. 177225) granted to G.R., S.D.K., M.Z. and M.H.