The molecular impact of omega 3 fatty acids on hepatic pro-inflammatory cytokine signaling

作者：Ventro George J; Yang Yingkui; Chen Min; Harmon Carroll M^*

来源：Journal of Pediatric Surgery, 2017, 52(6): 1020-1025.

DOI：10.1016/j.jpedsurg.2017.03.031

• Omegaven
• PNALD
• PON1
• IFALD
• IL-1
• TNF-alpha
• TGF-beta

Purpose: Parenteral nutrition associated liver disease (PNALD) develops in a subset of children receiving parenteral nutrition for intestinal failure. Omegaven(TM) is an omega-3 fatty acid (Omega 3FA) lipid emulsion high in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) that can lessen PNALD. Inflammatory cytokines (IL-1, TNF-alpha, TGF-beta) are elevated in PNALD and can decrease paraoxonase 1 protein expression (PON1). We sought to determine the effect of Omegaven(TM) , EPA, and DHA on inflammatory cytokines TNF-alpha, IL-1, and TGF-beta 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 T and Omega 3FA.
Methods: HepG2 cellswere cultured with each cytokine and Omegaven(TM) or EPA and DHA, or Intralipid T. P-Smad2/3 and PON1 protein levels were measured by Western blotting. ERK1/2 signaling was studied using homogenous time resolved fluorescence.
Results: Omegaven(TM) decreased TGF-beta mediated Smad2/3 signaling by 30% (70% of control 12, p < 0.03). Omegaven T decreased IL-1 and TNF-alpha 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 potentialmechanisms bywhichOmegaven T andO3FA can be hepatoprotective in the setting of PNALD by abating inflammatory cytokine signaling.

• 出版日期2017-6