ArticleLiver international : official journal of the International Association for the Study of the Liver2020
Dual targeting of hepatic fibrosis and atherogenesis by icosabutate, an engineered eicosapentaenoic acid derivative.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease.JHEP reports : innovation in hepatology · 2025Review
- High-density lipoproteins and non-alcoholic fatty liver disease.Atherosclerosis plus · 2023Article
- Article
- Protective Mechanism ofEvidence-based complementary and alternative medicine : eCAM · 2022Article
- Therapeutic and diagnostic targeting of fibrosis in metabolic, proliferative and viral disorders.Advanced drug delivery reviews · 2021Review
- Beneficial effects of elafibranor on NASH in E3L.CETP mice and differences between mice and men.Scientific reports · 2021Article
- Experimental and Investigational Targeted Therapies for the Management of Fibrosis in NASH: An Update.Journal of experimental pharmacology · 2021Review
- Dual targeting of hepatic fibrosis and atherogenesis by icosabutate, an engineered eicosapentaenoic acid derivative.Liver international : official journal of the International Association for the Study of the Liver · 2020Article
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18 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsWhile fibrosis stage predicts liver-associated mortality, cardiovascular disease (CVD) is still the major overall cause of mortality in patients with NASH. Novel NASH drugs should thus ideally reduce both liver fibrosis and CVD. Icosabutate is a semi-synthetic, liver-targeted eicosapentaenoic acid (EPA) derivative in clinical development for NASH. The primary aims of the current studies were to establish both the anti-fibrotic and anti-atherogenic efficacy of icosabutate in conjunction with changes in lipotoxic and atherogenic lipids in liver and plasma respectively.
methodsThe effects of icosabutate on fibrosis progression and lipotoxicity were investigated in amylin liver NASH (AMLN) diet (high fat, cholesterol and fructose) fed ob/ob mice with biopsy-confirmed steatohepatitis and fibrosis and compared with the activity of obeticholic acid. APOE*3Leiden.CETP mice, a translational model for hyperlipidaemia and atherosclerosis, were used to evaluate the mechanisms underlying the lipid-lowering effect of icosabutate and its effect on atherosclerosis.
resultsIn AMLN ob/ob mice, icosabutate significantly reduced hepatic fibrosis and myofibroblast content in association with downregulation of the arachidonic acid cascade and a reduction in both hepatic oxidised phospholipids and apoptosis. In APOE*3Leiden.CETP mice, icosabutate reduced plasma cholesterol and TAG levels via increased hepatic uptake, upregulated hepatic lipid metabolism and downregulated inflammation pathways, and effectively decreased atherosclerosis development.
conclusionsIcosabutate, a structurally engineered EPA derivative, effectively attenuates both hepatic fibrosis and atherogenesis and offers an attractive therapeutic approach to both liver- and CV-related morbidity and mortality in NASH patients.
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