Evidence map›Paper›PMID 35059746›Full record

ArticleJournal of molecular medicine (Berlin, Germany)2022

Recapitulating lipid accumulation and related metabolic dysregulation in human liver-derived organoids.

Ling Wang, Meng Li, Bingting Yu, Shaojun Shi, Jiaye Liu, Ruyi Zhang, Ibrahim Ayada, Monique M A Verstegen, Luc J W van der Laan, Maikel P Peppelenbosch and 2 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Journal of molecular medicine (Berlin, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

14 citing papers in PubMed, 28 citations in OpenAlex.

  1. Urinary Volatile Organic Compound Metabolites Are Associated With MASLD/MASH in Humans and Induce Steatosis in Liver Organoids.Liver international : official journal of the International Association for the Study of the Liver · 2026
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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

12 authors at 3 institutions in 2 countries.

Ling WangDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Meng LiDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Bingting YuDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Shaojun ShiDepartment of Surgery, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Jiaye LiuDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Ruyi ZhangDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Ibrahim AyadaDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Monique M A VerstegenDepartment of Surgery, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Luc J W van der LaanDepartment of Surgery, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Maikel P PeppelenboschDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.
Wanlu CaoDepartment of Oncology, Shanghai East Hospital, Tongji University, Shanghai, China. wanlu724576084@hotmail.com.
Qiuwei PanDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands. q.pan@erasmusmc.nl.ORCID 0000-0001-9982-6184
Erasmus MC · NLChinese Academy of Sciences · CNShanghai East Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fatty liver disease has grown into a major global health burden, attributed to multi-factors including sedentary lifestyle, obesogenic diet and prevalence of metabolic disorders. The lack of robust experimental models is hampering the research and therapeutic development for fatty liver disease. This study aims to develop an organoid-based 3D culture model to recapitulate key features of fatty liver disease focusing on intracellular lipid accumulation and metabolic dysregulation. We used human liver-derived intrahepatic cholangiocyte organoids and hepatocyte differentiated organoids. These organoids were exposed to lactate, pyruvate, and octanoic acid (LPO) for inducing lipid accumulation and mitochondrial impairment. Lipid accumulation resulted in alternations of gene transcription with major effects on metabolic pathways, including triglyceride and glucose level increase, which is consistent with metabolic changes in fatty liver disease patients. Interestingly, lipid accumulation affected mitochondria as shown by morphological transitions, alternations in expression of mitochondrial encoded genes, and reduction of ATP production. Meanwhile, we found treatment with obeticholic acid and metformin can alleviate fat accumulation in organoids. This study demonstrated that LPO exposure can induce lipid accumulation and associated metabolic dysregulation in human liver-derived organoids. This provides an innovative model for studying fatty liver disease and testing potential therapeutics. KEY MESSAGES: Lactate, pyruvate, and octanoic acid induce lipid accumulation in liver organoids. Organoids of human compared to mouse origin are more efficient in lipid accumulation. Lipid accumulation dysregulates metabolic pathway and impairs mitochondrial function. Demonstrating a proof-of-concept for testing medications in organoids.

Indexed as

HepatocytesOrganoidsAnimalsHumansLiverMicePyruvic AcidPyruvic AcidFatty liver diseaseLipid accumulationLiver organoidsMetabolic dysregulation

Identifiers

PMID35059746
OpenAlexW4205228703

What OpenQuestion holds

Textmetadata
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.