Evidence map›Paper›PMID 37902528›Full record

ArticleHepatology communications2023

Combined, elobixibat, and colestyramine reduced cholesterol toxicity in a mouse model of metabolic dysfunction-associated steatotic liver disease.

Michihiro Iwaki, Takaomi Kessoku, Kosuke Tanaka, Anna Ozaki, Yuki Kasai, Takashi Kobayashi, Asako Nogami, Yasushi Honda, Yuji Ogawa, Kento Imajo and 6 more

Open access · goldAbstract read
In one paragraph

Article in Hepatology communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.6field-weighted citation impact, top 27% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Hepatic bile acid accretion correlates with cholestatic liver injury and therapeutic response inAmerican journal of physiology. Gastrointestinal and liver physiology · 2024
    Article
  3. Exposure ofEnvironmental health perspectives · 2024
    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

16 authors at 4 institutions in 1 country.

Michihiro IwakiDepartment of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Takaomi KessokuDepartment of Palliative Medicine, International University Health and Welfare, Narita Hospital, Narita, Japan.
Kosuke TanakaDepartment of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Anna OzakiDepartment of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Yuki KasaiDepartment of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Takashi KobayashiDepartment of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Asako NogamiDepartment of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Yasushi HondaDepartment of Internal Medicine, Asakura Hospital, Konan-ku, Yokohama, Japan.
Yuji OgawaDepartment of Gastroenterology, National Hospital Organization Yokohama Medical Center, Totsuka-ku, Yokohama, Japan.
Kento ImajoDepartment of Gastroenterology, Shinyurigaoka General Hospital, Kawasaki, Japan.
Haruki UsudaDepartment of Pharmacology, Shimane University Faculty of Medicine, Shimane, Japan.
Koichiro WadaDepartment of Pharmacology, Shimane University Faculty of Medicine, Shimane, Japan.
Noritoshi KobayashiDepartment of Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Satoru SaitoDepartment of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Atsushi NakajimaDepartment of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Masato YonedaDepartment of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Yokohama City University · JPShimane University · JPInternational University of Health and Welfare · JPNational Hospital Organization · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCholesterol levels and bile acid metabolism are important drivers of metabolic dysfunction-associated steatohepatitis (MASH) progression. Using a mouse model, we investigated the mechanism by which cholesterol exacerbates MASH and the effect of colestyramine (a bile acid adsorption resin) and elobixibat (an apical sodium-dependent bile acid transporter inhibitor) concomitant administration on bile acid adsorption and MASH status.

methodsMice were fed a high-fat high-fructose diet with varying concentrations of cholesterol to determine changes in fatty liver according to liver status, water intake, defecation status, insulin resistance, bile acid levels, intestinal permeability, atherosclerosis (in apolipoprotein E knockout mice), and carcinogenesis (in diethylnitrosamine mice). Using small interfering ribonucleic acid (siRNA), we evaluated the effect of sterol regulatory element binding protein 1c (SREBP1c) knockdown on triglyceride synthesis and fatty liver status following the administration of elobixibat (group E), colestyramine (group C), or both (group EC).

resultsWe found greater reductions in serum alanine aminotransferase levels, serum lipid parameters, serum primary bile acid concentrations, hepatic lipid levels, and fibrosis area in EC group than in the monotherapy groups. Increased intestinal permeability and watery diarrhea caused by elobixibat were completely ameliorated in group EC. Group EC showed reduced plaque formation rates in the entire aorta and aortic valve of the atherosclerosis model, and reduced tumor counts and tumor burden in the carcinogenesis model.

conclusionsExcessive free cholesterol in the liver can promote fatty liver disease. Herein, combination therapy with EC effectively reduced free cholesterol levels in MASH model mice. Our study provides strong evidence for combination therapy as an effective treatment for MASH.

Indexed as

AtherosclerosisNon-alcoholic Fatty Liver DiseaseAnimalsBile Acids and SaltsCarcinogenesisCholestyramine ResinDipeptidesDisease Models, AnimalMiceThiazepinesBile Acids and SaltsCholestyramine ResinDipeptideselobixibatThiazepines

Identifiers

PMID37902528
PMCPMC10617934
OpenAlexW4388023974

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.