Evidence map›Paper›PMID 42234563›Full record

ArticleCell reports2026

CIDEB and CGI-58 differentially regulate liver lipid-droplet cholesterol to modulate metabolic dysfunction-associated steatohepatitis severity.

Ikki Sakuma, Rafael C Gaspar, Henrique N Morgan, Jie Zheng, Ali R Nasiri, Sylvie Dufour, Mario Kahn, Mateus T Guerra, Yuki Taki, Yusuke Kawashima and 7 more

Abstract read
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

17 authors.

Ikki SakumaDepartments of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Departments of Molecular Diagnosis, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan. Electronic address: ikki.sakuma@yale.edu.
Rafael C GasparDepartments of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
Henrique N MorganDepartments of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
Jie ZhengDepartments of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
Ali R NasiriDepartments of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
Sylvie DufourDepartments of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
Mario KahnDepartments of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
Mateus T GuerraDepartments of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
Yuki TakiDepartments of Molecular Diagnosis, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Yusuke KawashimaKazusa DNA Research Institute, Chiba 292-0818, Japan.
Dean YimlamaiDepartments of Pediatrics, Yale School of Medicine, New Haven, CT 06520, USA.
Mark PerelisIonis Pharmaceuticals, Carlsbad, CA, USA.
Daniel F VatnerDepartments of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
Kitt Falk PetersenDepartments of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
Varman T SamuelDepartments of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA; West Haven VA Medical Center, West Haven, CT, USA.
Tomoaki TanakaDepartments of Molecular Diagnosis, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Gerald I ShulmanDepartments of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA; Departments of Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: gerald.shulman@yale.edu.

Funding

Yale Diabetes Research CenterP30DK045735 · NIDDK · YALE UNIVERSITY · PI GERALD I SHULMAN · 1993 to 2026
$44.0M
Yale Liver CenterP30DK034989 · NIDDK · YALE UNIVERSITY · PI MICHAEL H NATHANSON, Mario Strazzabosco · 1986 to 2026
$31.1M
Effects of Hepatic Acetyl-CoA Carboxylase Inhibition on NAFLD and Hepatic Insulin ResistanceR01DK113984 · NIDDK · YALE UNIVERSITY · PI SHULMAN, GERALD I · 2017 to 2021
$3.7M
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 SHULMAN, GERALD I · 2019 to 2024
$2.7M
Mechanism of Renal Cortical Insulin ResistanceR01DK133143 · NIDDK · YALE UNIVERSITY · PI SHULMAN, GERALD I · 2022 to 2025
$2.3M
Deciphering Epithelial Signals in the Liver to Drive Inflammation and FibrosisR01DK129552 · NIDDK · YALE UNIVERSITY · PI YIMLAMAI, DEAN · 2021 to 2025
$2.2M
NIDDK NIH HHS P30 DK034989NIDDK NIH HHS P30 DK045735NIDDK NIH HHS R01 DK113984NIDDK NIH HHS R01 DK119968NIDDK NIH HHS R01 DK129552NIDDK NIH HHS R01 DK133143
6 · The paper itself

Abstract

Metabolic dysfunction-associated steatohepatitis (MASH) increases liver-related mortality, and new therapies targeting its underlying mechanisms are warranted. We examined whether two lipid-droplet proteins, CIDEB and CGI-58, exert opposing control over MASH by altering cholesterol in liver lipid droplets. Using antisense oligonucleotides, we silenced CIDEB or CGI-58 in the livers of C57BL/6J mice fed a choline-deficient, L-amino acid-defined high-fat diet. CIDEB silencing decreased both triglyceride and cholesterol levels in liver lipid droplets and lowered plasma transaminases and the number of crown-like structures. These protective effects were abrogated by cholesterol supplementation. Conversely, CGI-58 knockdown raised triglyceride and cholesterol levels and exacerbated MASH; bempedoic acid, a cholesterol-synthesis inhibitor, reversed these changes. Dual CIDEB/CGI-58 silencing confirmed that CGI-58 loss abrogated the protective effects of CIDEB knockdown. Our data establish liver lipid-droplet cholesterol as a critical determinant in MASH mediated by CIDEB and CGI-58 and demonstrate that CIDEB knockdown confers protection by enhancing CGI-58-dependent lipolysis.

Indexed as

1-Acylglycerol-3-Phosphate O-AcyltransferaseCholesterolFatty LiverLipid DropletsLiverAnimalsDiet, High-FatMaleMiceMice, Inbred C57BLTriglycerides1-Acylglycerol-3-Phosphate O-AcyltransferaseAbhd5 protein, mouseCholesterolTriglyceridesantisense oligonucleotideATGLCGI-58/ABHD5cholesterolcholine-deficient, L-amino acid-defined high-fat dietCIDEBCP: metabolismlipid-droplet cholesterollipid droplet proteinmetabolic dysfunction-associated steatohepatitis

Identifiers

PMID42234563
PMCPMC13373722

What Socratic holds

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LicenceCC BY-NC
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 Socratic graph.