Evidence map›Paper›PMID 31830357›Full record

ArticleJournal of veterinary internal medicine2020

Identification of potential drugs for treatment of hepatic lipidosis in cats using an in vitro feline liver organoid system.

Maya W Haaker, Hedwig S Kruitwagen, Arie B Vaandrager, Martin Houweling, Louis C Penning, Martijn R Molenaar, Monique E van Wolferen, Loes A Oosterhoff, Bart Spee, J Bernd Helms

Open access · goldAbstract read
In one paragraph

Article in Journal of veterinary internal medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 21% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Animal organoids as models for integrated One Health research.One health (Amsterdam, Netherlands) · 2026
    Review
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  11. Customized liver organoids as an advancedInternational journal of biological sciences · 2023
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  17. Organoids to model liver disease.JHEP reports : innovation in hepatology · 2021
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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

10 authors at 1 institution in 1 country.

Maya W HaakerDepartment of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Hedwig S KruitwagenDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Arie B VaandragerDepartment of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Martin HouwelingDepartment of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Louis C PenningDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Martijn R MolenaarDepartment of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Monique E van WolferenDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Loes A OosterhoffDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Bart SpeeDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.ORCID https://orcid.org/0000-0002-3981-8542
J Bernd HelmsDepartment of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.ORCID https://orcid.org/0000-0001-7311-3821
Utrecht University · NL

Funding

Winn Feline Foundation W17-015
6 · The paper itself

Abstract

backgroundHepatic lipidosis is increasing in incidence in the Western world, with cats being particularly sensitive. When cats stop eating and start utilizing their fat reserves, free fatty acids (FFAs) increase in blood, causing an accumulation of triacylglycerol (TAG) in the liver.

objectiveIdentifying potential new drugs that can be used to treat hepatic lipidosis in cats using a feline hepatic organoid system. ANIMALS: Liver organoids obtained from 6 cats.

methodsEight different drugs were tested, and the 2 most promising were further studied using a quantitative TAG assay, lipid droplet staining, and qPCR.

resultsBoth T863 (a diacylglycerol O-acyltransferase 1 [DGAT1] inhibitor) and 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR; an adenosine monophosphate kinase activator) decreased TAG accumulation by 55% (P < .0001) and 46% (P = .0003), respectively. Gene expression of perilipin 2 (PLIN2) increased upon the addition of FFAs to the medium and decreased upon treatment with AICAR but not significantly after treatment with T863. CONCLUSIONS AND CLINICAL IMPORTANCE: Two potential drugs useful in the treatment of hepatic lipidosis in cats were identified. The drug T863 inhibits DGAT1, indicating that DGAT1 is the primary enzyme responsible for TAG synthesis from external fatty acids in cat organoids. The drug AICAR may act as a lipid-lowering compound via decreasing PLIN2 mRNA. Liver organoids can be used as an in vitro tool for drug testing in a species-specific system and provide the basis for further clinical testing of drugs to treat steatosis.

Indexed as

Aminoimidazole CarboxamideAnimalsCat DiseasesCatsDiacylglycerol O-AcyltransferaseFatty Acids, NonesterifiedFatty LiverLipidosesLiverOrganoidsRibonucleotidesAICA ribonucleotideAminoimidazole CarboxamideDiacylglycerol O-AcyltransferaseFatty Acids, NonesterifiedRibonucleotidesAICARdiacylglycerol O-acyltransferase 1 inhibitorhepatic organoidsperilipin 2steatosis

Identifiers

PMID31830357
PMCPMC6979087
OpenAlexW2995484929

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.