Evidence map›Paper›PMID 38662778›Full record

ArticlePloS one2024

Increased hepatoprotective effects of the novel farnesoid X receptor agonist INT-787 versus obeticholic acid in a mouse model of nonalcoholic steatohepatitis.

Luciano Adorini, Kristoffer Rigbolt, Michael Feigh, Jonathan Roth, Mary Erickson

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Review
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

5 authors at 2 institutions in 2 countries.

Luciano AdoriniIntercept Pharmaceuticals, Inc., San Diego, California, United States of America.ORCID 0000-0001-8109-339X
Kristoffer RigboltGubra, Hørsholm, Denmark.
Michael FeighGubra, Hørsholm, Denmark.
Jonathan RothIntercept Pharmaceuticals, Inc., San Diego, California, United States of America.
Mary EricksonIntercept Pharmaceuticals, Inc., San Diego, California, United States of America.ORCID 0000-0002-6514-6073
Intercept Pharmaceuticals (United States) · USGubra (Denmark) · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The nuclear farnesoid X receptor (FXR), a master regulator of bile acid and metabolic homeostasis, is a key target for treatment of nonalcoholic steatohepatitis (NASH). This study compared efficacy of FXR agonists obeticholic acid (OCA) and INT-787 by liver histopathology, plasma biomarkers of liver damage, and hepatic gene expression profiles in the Amylin liver NASH (AMLN) diet-induced and biopsy-confirmed Lepob/ob mouse model of NASH. Lepob/ob mice were fed the AMLN diet for 12 weeks before liver biopsy and subsequent treatment with vehicle, OCA, or INT-787 for 8 weeks. Hepatic steatosis, inflammation, and fibrosis (liver lipids, galectin-3, and collagen 1a1 [Col1a1], respectively), as well as plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, were assessed. Hepatic gene expression was assessed in Lepob/ob mice that were fed the AMLN diet for 14 weeks then treated with vehicle, OCA, or INT-787 for 2 weeks. INT-787, which is equipotent to OCA but more hydrophilic, significantly reduced liver lipids, galectin-3, and Col1a1 compared with vehicle, and to a greater extent than OCA. INT-787 significantly reduced plasma ALT and AST levels, whereas OCA did not. INT-787 modulated a substantially greater number of genes associated with FXR signaling, lipid metabolism, and stellate cell activation relative to OCA in hepatic tissue. These findings demonstrate greater efficacy of INT-787 treatment compared with OCA in improving liver histopathology, decreasing liver enzyme levels, and enhancing gene regulation, suggesting superior clinical potential of INT-787 for the treatment of NASH and other chronic liver diseases.

Indexed as

Chenodeoxycholic AcidDisease Models, AnimalLiverNon-alcoholic Fatty Liver DiseaseReceptors, Cytoplasmic and NuclearAnimalsGalectin 3MaleMiceReceptor, Farnesoid X-ActivatedChenodeoxycholic AcidGalectin 3Lgals3 protein, mouseobeticholic acidReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and Nuclear

Identifiers

PMID38662778
PMCPMC11045142
OpenAlexW4395478502

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.