Evidence map›Paper›PMID 32841505›Full record

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.

Geurt Stokman, Anita M van den Hoek, Ditte Denker Thorbekk, Elsbet J Pieterman, Sanne Skovgård Veidal, Brittany Basta, Marta Iruarrizaga-Lejarreta, José W van der Hoorn, Lars Verschuren, Jimmy F P Berbée and 8 more

Open access · hybridAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.9field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Protective Mechanism ofEvidence-based complementary and alternative medicine : eCAM · 2022
    Article
  5. Review
  6. Article
  7. Review
  8. 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 · 2020
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 5 countries.

Geurt StokmanTNO Metabolic Health Research, Leiden, The Netherlands.
Anita M van den HoekTNO Metabolic Health Research, Leiden, The Netherlands.
Ditte Denker ThorbekkGubra, Hørsholm, Denmark.
Elsbet J PietermanTNO Metabolic Health Research, Leiden, The Netherlands.
Sanne Skovgård VeidalGubra, Hørsholm, Denmark.
Brittany BastaDivision of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Marta Iruarrizaga-LejarretaOWL Metabolomics, Parque Tecnológico de Bizkaia, Zamudio, Spain.
José W van der HoornTNO Metabolic Health Research, Leiden, The Netherlands.
Lars VerschurenTNO Microbiology & Systems Biology, Zeist, The Netherlands.
Jimmy F P BerbéeDepartment. of Medicine, Division of Endocrinology, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Patrick C N RensenDepartment. of Medicine, Division of Endocrinology, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Tore SkjaeretNorthSea Therapeutics BV, Amsterdam, The Netherlands.
Cristina AlonsoDivision of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Michael FeighGubra, Hørsholm, Denmark.
John J P KasteleinDepartment of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Scott L FriedmanDivision of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Hans M G PrincenTNO Metabolic Health Research, Leiden, The Netherlands.
David A FraserNorthSea Therapeutics BV, Amsterdam, The Netherlands.ORCID 0000-0001-7556-4351
Gubra (Denmark) · DKIcahn School of Medicine at Mount Sinai · USAIMM Therapeutics (Netherlands) · NLLeiden University Medical Center · NLAmsterdam UMC Location University of Amsterdam · NLEuskadiko Parke Teknologikoa · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

AtherosclerosisNon-alcoholic Fatty Liver DiseaseAnimalsButyratesDisease Models, AnimalEicosapentaenoic AcidHumansLiverLiver CirrhosisMiceMice, Inbred C57BLButyratesEicosapentaenoic Acidicosabutateapoptosisarachidonic acidatherosclerosislipotoxicityNASHoxidised phospholipids

Identifiers

PMID32841505
PMCPMC7702170
OpenAlexW3080587568

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.