ArticleCell death & disease2019
The cirrhotic liver is depleted of docosahexaenoic acid (DHA), a key modulator of NF-κB and TGFβ pathways in hepatic stellate cells.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- The Small Molecule H89 Facilitates Mesenchymal Stem Cell-derived Extracellular Vesicle Release and Optimizes Therapeutic Efficacy in Liver Regeneration.Journal of extracellular vesicles · 2026Article
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- Immune microenvironment changes of liver cirrhosis: emerging role of mesenchymal stromal cells.Frontiers in immunology · 2023Review
- Topical Administration of a Marine Oil Rich in Pro-Resolving Lipid Mediators Accelerates Wound Healing in DiabeticInternational journal of molecular sciences · 2022Article
- U1A is a positive regulator of the expression of heterologous and cellular genes involved in cell proliferation and migration.Molecular therapy. Nucleic acids · 2022Article
- Repeated trans-arterial treatments of LDL-DHA nanoparticles induce multiple pathways of tumor cell death in hepatocellular carcinoma bearing rats.Frontiers in oncology · 2022Article
- Myriocin Treatment Reverses Alcohol-Induced Alterations in Polyunsaturated Fatty Acid-Containing Phospholipid Expression in the Liver.Nutrition and metabolic insights · 2022Article
- Maresin-1 Prevents Liver Fibrosis by Targeting Nrf2 and NF-κB, Reducing Oxidative Stress and Inflammation.Cells · 2021Article
- Human hepatocyte-derived extracellular vesicles attenuate the carbon tetrachloride-induced acute liver injury in mice.Cell death & disease · 2021Article
- Review
- Liver Lipids of Patients with Hepatitis B and C and Associated Hepatocellular Carcinoma.International journal of molecular sciences · 2021Article
- Emerging Treatment Options for Sarcopenia in Chronic Liver Disease.Life (Basel, Switzerland) · 2021Review
- Effect of docosahexaenoic acid plus insulin on atherosclerotic human endothelial cells.Journal of inflammation (London, England) · 2021Article
- Hepatic Unsaturated Fatty Acids Are Linked to Lower Degree of Fibrosis in Non-alcoholic Fatty Liver Disease.Frontiers in medicine · 2021Article
- Omega-3 polyunsaturated fatty acids: a promising approach for the management of oral lichen planus.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2020Review
- Kidney and lung tissue modifications after BDL-induced liver injury in mice are associated with increased expression of IGFBPrP1 and activation of the NF-κB inflammation pathway.International journal of clinical and experimental pathology · 2020Article
- Article
- A Nutraceutical Rich in Docosahexaenoic Acid Improves Portal Hypertension in a Preclinical Model of Advanced Chronic Liver Disease.Nutrients · 2019Article
- Liver Cirrhosis Patients Who Had Normal Liver Function Before Liver Cirrhosis Development Have the Altered Metabolic Profiles Before the Disease Occurrence Compared to Healthy Controls.Frontiers in physiology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver cirrhosis results from chronic hepatic damage and is characterized by derangement of the organ architecture with increased liver fibrogenesis and defective hepatocellular function. It frequently evolves into progressive hepatic insufficiency associated with high mortality unless liver transplantation is performed. We have hypothesized that the deficiency of critical nutrients such as essential omega-3 fatty acids might play a role in the progression of liver cirrhosis. Here we evaluated by LC-MS/MS the liver content of omega-3 docosahexaenoic fatty acid (DHA) in cirrhotic patients and investigated the effect of DHA in a murine model of liver injury and in the response of hepatic stellate cells (HSCs) (the main producers of collagen in the liver) to pro-fibrogenic stimuli. We found that cirrhotic livers exhibit a marked depletion of DHA and that this alteration correlates with the progression of the disease. Administration of DHA exerts potent anti-fibrogenic effects in an acute model of liver damage. Studies with HSCs show that DHA inhibits fibrogenesis more intensely than other omega-3 fatty acids. Data from expression arrays revealed that DHA blocks TGFβ and NF-κB pathways. Mechanistically, DHA decreases late, but not early, SMAD3 nuclear accumulation and inhibits p65/RelA-S536 phosphorylation, which is required for HSC survival. Notably, DHA increases ADRP expression, leading to the formation of typical quiescence-associated perinuclear lipid droplets. In conclusion, a marked depletion of DHA is present in the liver of patients with advanced cirrhosis. DHA displays anti-fibrogenic activities on HSCs targeting NF-κB and TGFβ pathways and inducing ADPR expression and quiescence in these cells.
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