Evidence mapPaperPMID 40310463Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction-associated steatohepatitis.

Ikki Sakuma, Rafael C Gaspar, Ali R Nasiri, Sylvie Dufour, Mario Kahn, Jie Zheng, Traci E LaMoia, Mateus T Guerra, Yuki Taki, Yusuke Kawashima and 11 more

Erratum issuedAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
field-weighted citation impact
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

21 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Mechanisms and therapeutic insights into MASH-associated fibrosis.Trends in endocrinology and metabolism: TEM · 2026
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Cholesterol-containing lipid crystals can directly stiffen the rat steatotic liver before fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Location, location, location: Cholesterol in lipid droplets as a driver of MASH progression.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Ikki SakumaDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06520.
Rafael C GasparDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06520.
Ali R NasiriDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06520.
Sylvie DufourDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06520.ORCID 0000-0002-0402-5403
Mario KahnDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06520.
Jie ZhengDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06520.
Traci E LaMoiaDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06520.ORCID 0000-0002-8376-2240
Mateus T GuerraDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06520.ORCID 0000-0002-8187-2753
Yuki TakiDepartment of Molecular Diagnosis, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Yusuke KawashimaDepartment of Applied Genomics, Kazusa deoxyribonucleic acid Research Institute, Chiba 292-0818, Japan.
Dean YimlamaiDepartment of Pediatrics, Yale School of Medicine, New Haven, CT 06520.ORCID 0000-0002-7936-7168
Mark PerelisIonis Pharmaceuticals, Carlsbad, CA 92010.
Daniel F VatnerDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06520.ORCID 0000-0003-2073-0273
Kitt Falk PetersenDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06520.ORCID 0000-0003-2664-670X
Maximilian HuttaschInstitute for Clinical Diabetology, German Diabetes Center (Deutsches Diabetes-Zentrum), Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf 40225, Germany.
Birgit KnebelGerman Center for Diabetes Research (Deutsche Zentrum für Diabetesforschung e.V.), Partner Düsseldorf, München-Neuherberg 85764, Germany.
Sabine KahlInstitute for Clinical Diabetology, German Diabetes Center (Deutsches Diabetes-Zentrum), Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf 40225, Germany.
Michael RodenInstitute for Clinical Diabetology, German Diabetes Center (Deutsches Diabetes-Zentrum), Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf 40225, Germany.
Varman T SamuelDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06520.
Tomoaki TanakaDepartment of Molecular Diagnosis, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.ORCID 0000-0002-9761-1750
Gerald I ShulmanDepartment of Internal Medicine, Yale School of Medicine, New Haven, CT 06520.ORCID 0000-0003-1529-5668

Funding

Yale Liver CenterP30DK034989 · NIDDK · YALE UNIVERSITY · 1986 to 2025
$10.2M
Yale Diabetes Research CenterP30DK045735 · YALE UNIVERSITY · 1993 to 2025
$10.2M
INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDT32GM007324 · YALE UNIVERSITY · 1987 to 2005
$1.3M
Mechanism of Renal Cortical Insulin ResistanceR01DK133143 · YALE UNIVERSITY · 2025 to 2025
$573k
Development of Controlled Release Mitochondrial Protonophore (CRMP) as a Novel Treatment for Type-2 Diabetes and Non-Alcoholic Steatohepatitis in Dysmetabolic Non-Human PrimatesR01DK119968 · NIDDK · YALE UNIVERSITY · PI GERALD I SHULMAN · 2023 to 2023
$532k
Deciphering Epithelial Signals in the Liver to Drive Inflammation and FibrosisR01DK129552 · YALE UNIVERSITY · 2025 to 2025
$419k
HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) F31DK126362HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) P30 DK34989Manpei Suzuki Diabetes Foundation N/ANIDDK NIH HHS F31 DK126362NIDDK NIH HHS P30 DK034989NIDDK NIH HHS P30 DK045735NIDDK NIH HHS R01 DK113984NIDDK NIH HHS R01 DK119968NIDDK NIH HHS R01 DK129552NIDDK NIH HHS R01 DK133143NIGMS NIH HHS T32 GM007324
6 · The paper itself

Abstract

Metabolic dysfunction-associated steatohepatitis (MASH) represents a progressive form of steatotic liver disease which increases the risk for fibrosis and advanced liver disease. The accumulation of discrete species of bioactive lipids has been postulated to activate signaling pathways that promote inflammation and fibrosis. However, the key pathogenic lipid species is a matter of debate. We explored candidates using various dietary, molecular, and genetic models. Mice fed a choline-deficient L-amino acid-defined high-fat diet (CDAHFD) developed steatohepatitis and manifested early markers of liver fibrosis associated with increased cholesterol content in liver lipid droplets within 5 d without any changes in total liver cholesterol content. Treating mice with antisense oligonucleotides against

Indexed as

CholesterolFatty LiverLipid DropletsLiverAnimalsDiet, High-FatHumansLipid MetabolismLiver CirrhosisMaleMiceMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseCholesterolcholesterolCoenzyme A synthaselipid dropletmetabolic dysfunction–associated steatohepatitis (MASH)phosphatidylcholine

Identifiers

PMID40310463
PMCPMC12067271

What Socratic holds

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Registered trials

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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 Socratic graph.