Evidence map›Paper›PMID 38340721›Full record

ArticleCell metabolism2024

DGAT2 inhibition blocks SREBP-1 cleavage and improves hepatic steatosis by increasing phosphatidylethanolamine in the ER.

Shunxing Rong, Mingfeng Xia, Goncalo Vale, Simeng Wang, Chai-Wan Kim, Shili Li, Jeffrey G McDonald, Arun Radhakrishnan, Jay D Horton

Open access · hybridAbstract read
In one paragraph

Article in Cell metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
23.9field-weighted citation impact, top 1% 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

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Observational
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Multi-Organ Transcriptomic Analysis of Greater Amberjack (Animals : an open access journal from MDPI · 2026
    Article
  16. Differential Effects ofNutrients · 2026
    Article
  17. Article
  18. Article
  19. Article
  20. Review

3 more citing papers are in PubMed but not listed here.

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

9 authors at 2 institutions in 2 countries.

Shunxing RongDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA; Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.
Mingfeng XiaDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA; Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Goncalo ValeDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA; Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.
Simeng WangDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.
Chai-Wan KimDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA; Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.
Shili LiDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.
Jeffrey G McDonaldDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA; Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.
Arun RadhakrishnanDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA.
Jay D HortonDepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA; Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA. Electronic address: jay.horton@utsouthwestern.edu.
The University of Texas Southwestern Medical Center · USThe First Affiliated Hospital, Sun Yat-sen University · CN

Funding

UT Southwestern Center for Translational MedicineUL1TR003163 · NCATS · UT SOUTHWESTERN MEDICAL CENTER · PI TOTO, ROBERT DANIEL · 2021 to 2025
$39.3M
Tissue Culture & Antibody Production CoreP01HL160487 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI Helen Haskell Hobbs · 2022 to 2026
$14.9M
UT Southwestern NORCP30DK127984 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI Jeff G McDonald · 2022 to 2026
$7.4M
UT GASTROENTEROLOGY/HEPATOLOGY RESEARCH TRAINING PROGRAMT32DK007745 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI Rodney E Infante · 1997 to 2026
$6.8M
Oxysterol Regulation of Microbial PathogenesisR01AI158357 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI ALTO, NEAL MATHEW, RADHAKRISHNAN, ARUN · 2021 to 2025
$2.9M
NCATS NIH HHS UL1 TR003163NHLBI NIH HHS P01 HL160487NIAID NIH HHS R01 AI158357NIDDK NIH HHS P30 DK127984NIDDK NIH HHS T32 DK007745
6 · The paper itself

Abstract

Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step of triglyceride (TG) synthesis. DGAT2 deletion in mice lowers liver TGs, and DGAT2 inhibitors are under investigation for the treatment of fatty liver disease. Here, we show that DGAT2 inhibition also suppressed SREBP-1 cleavage, reduced fatty acid synthesis, and lowered TG accumulation and secretion from liver. DGAT2 inhibition increased phosphatidylethanolamine (PE) levels in the endoplasmic reticulum (ER) and inhibited SREBP-1 cleavage, while DGAT2 overexpression lowered ER PE concentrations and increased SREBP-1 cleavage in vivo. ER enrichment with PE blocked SREBP-1 cleavage independent of Insigs, which are ER proteins that normally retain SREBPs in the ER. Thus, inhibition of DGAT2 shunted diacylglycerol into phospholipid synthesis, increasing the PE content of the ER, resulting in reduced SREBP-1 cleavage and less hepatic steatosis. This study reveals a new mechanism that regulates SREBP-1 activation and lipogenesis that is independent of sterols and SREBP-2 in liver.

Indexed as

Diacylglycerol O-AcyltransferaseNon-alcoholic Fatty Liver DiseaseAnimalsEndoplasmic ReticulumLiverMicePhosphatidylethanolaminesSterol Regulatory Element Binding Protein 1TriglyceridesDGAT2 protein, mouseDiacylglycerol O-AcyltransferasePhosphatidylethanolaminesSrebf1 protein, mouseSterol Regulatory Element Binding Protein 1TriglyceridesDGAT2diacylglycerol acyltransferase 2hepatic steatosislipogenesisPEphosphatidylethanolamineSREBPs

Identifiers

PMID38340721
PMCPMC10939742
OpenAlexW4391692569

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.