The Molecular Impact of Omega 3 Fatty Acids on Hepatic Pro-inflammatory Cytokine Signaling

Abstract Purpose Parenteral nutrition associated liver disease (PNALD) develops in a subset of children receiving parenteral nutrition for intestinal failure. Omegaven™ is an omega-3 fatty acid (Ω3FA) lipid emulsion high in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) that can lessen P...

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Bibliographic Details
Published in:Journal of pediatric surgery 2017-06, Vol.52 (6), p.1020-1025
Main Authors: Ventro, George J, Yang, Yingkui, Chen, Min, Harmon, Carroll M
Format: Article
Language:English
Subjects:
Aryldialkylphosphatase - metabolism
Biomarkers - metabolism
Blotting, Western
Cytokines - metabolism
Docosahexaenoic Acids - pharmacology
Eicosapentaenoic Acid - pharmacology
Fish Oils - pharmacology
Hep G2 Cells
Humans
IFALD
IL-1
Liver - drug effects
Liver - metabolism
Omegaven
Pediatrics
PNALD
PON1
Protective Agents - pharmacology
Signal Transduction - drug effects
Surgery
TGF-β
TNF-α
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Summary:Abstract Purpose Parenteral nutrition associated liver disease (PNALD) develops in a subset of children receiving parenteral nutrition for intestinal failure. Omegaven™ is an omega-3 fatty acid (Ω3FA) lipid emulsion high in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) that can lessen PNALD. Inflammatory cytokines (IL-1, TNF-α, TGF-β) are elevated in PNALD and can decrease paraoxonase 1 protein expression (PON1). We sought to determine the effect of Omegaven™, EPA, and DHA on inflammatory cytokines TNF-α, IL-1, and TGF-β via ERK1/2 and p-Smad2/3 signaling pathways as well as the changes in intracellular PON1 protein expression as a potential mechanism explaining the protective effects of Omegaven™ and Ω3FA. Methods HepG2 cells were cultured with each cytokine and Omegaven™, or EPA and DHA, or Intralipid™. P-Smad2/3 and PON1 protein levels were measured by Western blotting. ERK1/2 signaling was studied using homogenous time resolved fluorescence. Results Omegaven™ decreased TGF-β mediated Smad2/3 signaling by 30% (70% of control ± 12, p < 0.03). Omegaven™ decreased IL-1 and TNF-α mediated ERK1/2 signaling (0.49 fold ± 0.09, p < 0.05 and 0.22 ± 0.05, p < 0.05) compared to control. Conclusion Our results describe potential mechanisms by which Omegaven™ and Ω3FA can be hepatoprotective in the setting of PNALD by abating inflammatory cytokine signaling.
ISSN:0022-3468
1531-5037
DOI:10.1016/j.jpedsurg.2017.03.031