Molecular impact of omega 3 fatty acids on lipopolysaccharide-mediated liver damage

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Potective role elucidated thanks to pERK assay kit. A new signaling pathway to target Chronic liver diseases

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Parenteral nutrition (PN) is a life-saving therapeutic modality for patients with intestinal failure. Lifelong PN is also needed by many patients suffering from short bowel syndrome. However, prolonged PN is associated with short-term and long-term complications, notably affecting the liver.Parenteral nutrition-associated liver disease (PNALD) is one of the long-term complications associated with the use of intravenous lipid emulsion to prevent essential fatty acid deficiency in those patients. Parenteral nutrition-associated liver disease (PNALD) is the most devastating complication of long-term parenteral nutrition therapy. Because its progression is typically subtle, and its long-term consequences generally underacknowledged, PNALD is often recognized too late, when liver injury is irreversible. Recent evidence suggests that omega-3 fatty acids have a beneficial role regarding this pathology.In the case of chronic diseases, with a persistent pro-inflammatory context, it is always difficult to identify the triggering factors that lead to damage. Part of the mystery is revealed in this article by George Ventro et al, from the State University of New York at Buffalo.From human hepatic HepG2 cancer cells treated with LPS, George Ventro characterized the molecular mechanism of omega-3. He identified the different components and highlighted the signaling pathway involved.This study clearly shows another protective role of omega-3 fatty acids and offers a new option for further investigation into LPS-mediated hepatocyte injury and liver damage.It also represents a potential new direction for studying other chronic liver diseases, such as NASH/NAFLD.


BACKGROUND: Growing evidence suggests that omega 3 fatty acid containing lipid emulsions have a beneficial effect on parenteral nutrition associated liver disease (PNALD). However, the cellular and molecular mechanisms responsible for this effect are unclear. In this study, we investigated whether Omegaven™ fish oil emulsion could inhibit lipopolysaccharidase (LPS) mediated liver damage.
METHODS: We examined the effects of Omegaven™ and LPS alone and synergistically on hepatic paraoxonase 1 (PON1), a potent antioxidant protein, ERK1/2 activity, and TLR4 regulation.
RESULTS: LPS did not alter PON1 release from HepG2 cells but did significantly decrease PON1 protein synthesis (44%, P<0.05). Omegaven™ alone had no direct effect on PON1 release. However, it did significantly reverse LPS-mediated decrease in PON1 protein levels (control: 100%; LPS alone: 56+/4%; LPS+Omegaven™: 87+/6%, P<0.05). Furthermore, molecular analysis indicated that Omegaven™ blocked LPS-mediated increase in ERK1/2 activity (35% increase), an important LPS signal transduction pathway. TLR4, the receptor for LPS, was down-regulated in the presence of Omegaven™. CONCLUSION: Omegaven™ may be beneficial in patients with PNAC because of its ability to reverse LPS-mediated inhibition of antioxidant promoting PON1 expression, and this activity may be in part mediated by the ERK1/2 pathway.


Journal of Pediatric Surgery. 2016 Jun;52(6):1039-1043.

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